U.S. patent application number 12/108063 was filed with the patent office on 2008-09-11 for devices and methods for spine repair.
This patent application is currently assigned to Promethean Surgical Devices, LLC. Invention is credited to Robert M. Arcangeli, Michael T. Milbocker, Jeffrey A. Wilson.
Application Number | 20080221628 12/108063 |
Document ID | / |
Family ID | 34437250 |
Filed Date | 2008-09-11 |
United States Patent
Application |
20080221628 |
Kind Code |
A1 |
Milbocker; Michael T. ; et
al. |
September 11, 2008 |
DEVICES AND METHODS FOR SPINE REPAIR
Abstract
Surgical methods of repairing defects and deficiencies in the
spine are disclosed. The methods involve delivering a single part
in-situ polymerizing fluid to (i) close a weakened segment or
fissure in the annulus fibrosus, (ii) strengthen the annulus, (iii)
replace or augment the disc nucleus, or (iv) localize a disc
prosthesis. The methods may include placing a delivery conduit
adjacent to the repair site and providing a liquid tissue adhesive
to bond to and repair a disc defect or deficiency
Inventors: |
Milbocker; Michael T.;
(Holliston, MA) ; Wilson; Jeffrey A.; (Wrentham,
MA) ; Arcangeli; Robert M.; (Westborough,
MA) |
Correspondence
Address: |
RISSMAN JOBSE HENDRICKS & OLIVERIO, LLP
100 Cambridge Street, Suite 2101
BOSTON
MA
02114
US
|
Assignee: |
Promethean Surgical Devices,
LLC
Woburn
MA
|
Family ID: |
34437250 |
Appl. No.: |
12/108063 |
Filed: |
April 23, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10873899 |
Jun 22, 2004 |
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12108063 |
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60483186 |
Sep 29, 2003 |
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60483260 |
Nov 17, 2003 |
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60516999 |
Nov 4, 2003 |
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Current U.S.
Class: |
606/86R ;
604/509; 606/192; 606/92 |
Current CPC
Class: |
A61B 17/1604 20130101;
A61B 17/1671 20130101; A61B 17/00491 20130101; A61B 17/8897
20130101; A61B 17/0057 20130101; A61B 17/1637 20130101; A61B 50/30
20160201 |
Class at
Publication: |
606/86.R ;
606/192; 606/92; 604/509 |
International
Class: |
A61F 5/00 20060101
A61F005/00; A61M 29/00 20060101 A61M029/00; A61B 17/58 20060101
A61B017/58; A61M 31/00 20060101 A61M031/00 |
Claims
1-13. (canceled)
14. A method of reinforcing a spinal annulus, the method comprising
the steps of: accessing the disc containing the annulus to be
reinforced; advancing a catheter in the annulus fibrosus in an
orientation substantially parallel to and within two or more layers
of the annulus; introducing a wire or ribbon through the catheter,
or deploying a balloon on the tip of the catheter, to create at
least one of a pocket, a cavity, and a delamination within the
annulus; extending the pocket, cavity or delamination to at least
partially circumnavigate the annulus; introducing, through the same
or another catheter, a tube for delivering a tissue adhesive; and
gradually withdrawing the tube and catheter while filling said
pocket, cavity, or delamination to bind the two or more layers of
the annulus with the tissue adhesive.
15. The method of claim 14, further comprising allowing the
adhesive to cure to form a hydrophilic implant within two or more
layers of the pocket, cavity, or delamination.
16. The method of claim 15, wherein the curable adhesive is
characterized in being hydrophilic; reactive with functional groups
normally found on tissue surfaces so as to bond to tissue; and
capable of self-curing in the presence of water and in the absence
of added reactive materials or chain extenders, to form a solid
material adherent to at least one tissue surface.
17. The method of claim 14, wherein the step of filling said
pocket, cavity, or delamination with the tissue adhesive comprises
inserting an injector through the tube into one or both of the
annulus and the nuclear space; and injecting a controlled amount of
the tissue adhesive.
18. The method of claim 17 wherein the injector is bendable.
19. The method of claim 17 wherein a tip of the injector is
selectable for penetration of tissue or for sliding on a fissure
plane.
20. The method of claim 17 wherein multiple injections of adhesive
polymer are performed.
21. The method of claim 20 wherein the injector is moved between
injections.
22. The method of claim 14 wherein the tissue adhesive is naturally
liquid at room or body temperature.
23. The method of claim 14 wherein the tissue adhesive contains
water or an aqueous solution in the range of about 5% to about 95%
by volume.
24. The method of claim 14 wherein the tissue adhesive swells in
body fluids.
25. The method of claim 14 wherein the tissue adhesive comprises a
water-soluble polyether polyol.
26. The method of claim 28 wherein the excess polyisocyanate has a
molecular weight less than about 1000 Daltons.
27. (canceled)
28. The method of claim 14 wherein the tissue adhesive comprises
branched polyether polyols with polyisocyanate caps and excess
polyisocyanate.
29. The method of claim 14 wherein the defect repair is reinforcing
comprises one or more of closing a tear, window or fissure in an
annulus; re-connection between layers of an annulus.
30. The method of claim 17 wherein the injector further comprises
visualization means.
31. The method of claim 17 wherein the injector detects
pressure.
32. The method of claim 14 wherein the tissue adhesive comprises
one or more of contrast or visualization media, electrolytes,
volume-control polymers, fillers or reinforcing materials,
pharmaceutical or therapeutic agents including disinfectants, and
nucleolytic agents including enzymes and chemicals.
33. (canceled)
34. The method of claim 14, further comprising the step of filling
a nuclear space with the tissue adhesive.
Description
[0001] This application claims the benefit of the priority of U.S.
Provisional applications 60/483,186, filed Jun. 23, 2003 and
60/516,999, filed Nov. 4, 2003, which are hereby incorporated in
their entirety by reference in jurisdictions permitting the
same.
TECHNICAL FIELD
[0002] This disclosure relates to methods and devices for modifying
intervertebral disc tissue, spaces, and structure. More
particularly, the methods disclosed relate to the treatment of
weakening or rents of the annulus, disc nucleus insufficiency, and
localization of disc prosthetics, using open and minimally invasive
techniques. The preferred compositions for effecting repair are
single-part, in-situ polymerizing self-curing adhesive
compositions.
BACKGROUND
[0003] A. Treatment of Spinal Disc Abnormalities Intervertebral
disc abnormalities are common in the population and cause
considerable pain, particularly if they affect adjacent nerves.
Disc abnormalities result from trauma, wear, metabolic disorders
and the aging process and include degenerative discs, localized
tears or fissures in the annulus fibrosus, localized disc
herniations with contained or escaped extrusions, and chronic,
circumferential bulging discs. Disc fissures occur as a
degeneration of fibrous components of the annulus fibrosus. Rather
minor activities such as sneezing, bending or simple attrition can
tear degenerated annulus fibers and create a fissure. The fissures
may be further complicated by extrusion of nucleus pulposus
material into or beyond the annulus fibrosus. Difficulties can
still present even when there is no visible extrusion, due to
biochemicals within the disc irritating surrounding structures and
nerves. Initial treatment includes bed rest, pain killers and
muscle relaxants, but these measures rarely correct the underlying
cause. Surgical treatments include reduction of pressure on the
annulus by removing some of the interior nucleus pulposus material
by percutaneous nucleotomy. Surgical treatments meant to cure the
underlying cause include spinal fusion with screws, rods and fusion
cages. Devices and procedures involving screws, rods and plates are
disclosed in the following U.S. Pat. Nos., as well as others:
Errico 37,665; 5,733,286; 5,549,608; 5,554,157; 5,876,402;
5,817,094; 5,690,630; 5,669,911; 5,647,873; 5,643,265; 5,607,426;
5,531,746 and 5,520,690; Metz-Stavenhagen 6,261,287; Puno
5,474,555; Byrd 5,446,237; Biedermann 5,672,176 and 5,443,467;
Cotrel 4,815,453 and 5,005,562; Jackson 5,591,165; Harms 4,946,458;
5,092,867; 5,207,678 and 5,196,013; Mellinger 5,624,442; Sherman
5,885,286; 5,797,911 and 5,879,350; Morrison 5,891,145; Tatar
5,910,142; Nicholas 6,090,111; and Yuan 6,565,565. Fusion cages and
related procedures are disclosed in Bagby U.S. Pat. No. 4,501,269;
Michelson U.S. Pat. Nos. 5,015,247 and 5,797,909; Ray U.S. Pat. No.
6,042,582 and Kuslich U.S. Pat. Nos. 5,489,308; 6,287,343 and
5,700,291. Proposed disc replacement devices are disclosed in the
following U.S. Pat. Nos.: Middleton 6,315,797; Marnay 5,314,477;
Stubstad 3,867,728; Keller 4,997,432; and Buettner-Janz
4,759,766.
[0004] A contained disc herniation is not associated with free
nucleus fragments migrating to the spinal canal. However, a
contained disc herniation can still protrude and irritate
surrounding structures, for example by applying pressure to spinal
nerves. Escaped nucleus pulposus can chemically irritate neural
structures. Current treatment methods include reduction of pressure
on the annulus by removing some of the interior nucleus pulposus
material by percutaneous nucleotomy. See, for example, Kambin U.S.
Pat. No. 4,573,448. Complications include disc space infection,
nerve root injury, hematoma formation, instability of the adjacent
vertebrae and collapse of the disc from decrease in height. It has
been proposed to treat weakening due to nucleus pulposus deficiency
by inserting preformed hydrogel implants. See, Ray U.S. Pat. Nos.
4,772,287; 4,904,260 and, 5,562,736 and Bao U.S. Pat. No.
5,192,326.
[0005] Circumferential bulging of the disc also can result in
chronic disc weakening. The joint can become mechanically less
stable. As the bulging disc extends beyond its normal
circumference, the disc height is compromised and nerve roots are
compressed. In some cases osteophytes form on the outer surface of
the disc and further encroach on the spinal canal and channels
through which nerves pass. The condition is known as lumbar
spondylosis. Continued disc degeneration can resulting in one
vertebral body segment approaching and possibly contacting an
adjacent vertebral body segment.
[0006] Treatment for segmental instability include bed rest, pain
medication, physical therapy and steroid injection. Spinal fusion
is the final therapy performed with or without discectomy. Other
treatment includes discectomy alone or disc decompression with or
without fusion. Nucleotomy can be performed by removing some of the
nucleus matter to reduce pressure on the annulus. Complications
include disc space infection, nerve root injury, hematoma
formation, and instability of adjacent vertebrae. New fixation
devices include pedicle screws and interbody fusion cages. Studies
on fixation show success rates between 50% and 67% for pain
improvement, and a significant number of patients have more pain
postoperatively.
[0007] Delivery of tissue adhesives to the spine in a minimally
invasive manner have been disclosed, and include procedures for
restoring structural integrity to vertebral bodies. See Scribner
U.S. Pat. Nos. 6,241,734 and 6,280,456; Reiley U.S. Pat. Nos.
6,248,110 and 6,235,043; Boucher U.S. Pat. No. 6,607,554 and
Bhatnagar 6,395,007. Methods of repairing the spinal disc or
portions thereof are disclosed in Cauthern U.S. Pat. No. 6,592,625,
Haldimann U.S. Pat. No. 6,428,576, Trieu U.S. Pat. No. 6,620,196
and Milner U.S. Pat. No. 6,187,048.
[0008] B. Surgical Approaches to the Spine
[0009] The spine may be approached in open surgery using posterior,
anterior or lateral approaches. The following is a brief
description of several proposed surgical approaches which may be
used to gain access to the spine in a less invasive manner to treat
spinal insufficiency.
[0010] Posterior Lateral Approach Methods for disc access include
laminectomy, a procedure wherein a channel is made from the dorsal
side of the patient's back to the lumbar lamina of the disc. Blood
vessels, ligaments, major back support muscles and spinal nerves
located around the dural sac are retracted. Once the channel has
been cleared, the standard procedure is to cut a hole in the disc
capsule and pass instruments into the disc interior. This approach
creates a defect that is oriented toward spinal nerves, thus
typically the nucleus is completely removed to prevent extrusion of
nuclear material and subsequent pressure on these nerves.
Alternatively, under visual magnification with an operating
microscope or operating loupe, small diameter microsurgical
instruments can access the disc without cutting bone. It is
possible to bypass the nerves and blood vessels entirely by
inserting a cannula through the patient's side above the pelvic
crest to reach a predetermined position along the lumbar portion of
the spine. This procedure can be guided with use of
fluoroscopy.
[0011] Kambin U.S. Pat. No. 4,573,448 describes a posterior lateral
approach performed under local anesthesia by the insertion of a
cannulated trocar over a guide wire extending through the patient's
back toward a target disc at an angle of approximately 35 degrees
with respect to the patient's perpendicular line. In particular, a
hollow needle with a stylet is inserted at a location spaced from
the midline so as to form a 35 degree angle in an oblique
direction. When the needle reaches the annulus fibrosis it is
withdrawn after a guide wire is introduced through the needle to
the disc. A cannulated, blunt-tipped trocar is passed over the
guide wire until the tip reaches the annulus. The guide wire is
withdrawn. A closely-fitting, thin-walled cannula is passed over
the trocar until it reaches the annulus. The trocar can be
withdrawn. Cutting instruments or a punch can be used to expose the
nucleus.
[0012] Paramedian Transabdominal Procedure In this procedure the
patient is in the supine or lithotomy position. This transabdominal
procedure involves splitting the paramedian rectus, retracting the
bowel, incising the peritoneum on the posterior wall of the
abdominal cavity and accessing the anterior spine. Alternatively,
the anterior rectus sheath is exposed of the left rectus muscle.
The anterior rectus sheath is incised to expose the body of the
rectus muscle. The rectus muscle is then mobilized over an adequate
length, preferably symmetrical with the incision, and the rectus is
retracted medially. The posterior rectus sheath is cut to expose
the peritoneum. The peritoneum is pushed aside and dissected to
expose the psoas muscle. The ureter and the left iliac vessels are
mobilized. The rectus muscle, ureter, iliac vessels, and peritoneum
are retracted laterally to expose the lumbar region. For repair to
lumbar vertebrae L3-4 and L4-5, access should be made to the left
of the aorta and inferior vena cava, between the aorta and the
psoas muscle, and through the posterior peritoneum and fatty
tissue. In some cases it may be necessary to transverse the psoas
muscle. For access to sites between L5 and S-1, the dissection is
closer to the midline between the iliac branches of the great
vessels.
[0013] Lateral Retroperitoneal Procedure The retroperitoneal
procedure involves placing the patient in the right lateral
recumbent position and making an incision in the abdomen at the
border of the rectus muscle and subsequent dissection down to
identify the peritoneum. Dissection can be performed bluntly or may
be facilitated using a balloon cannula or expanding cannula as
described by Bonutti (U.S. Pat. No. 5,514,153). The resulting
retroperitoneal cavity can be held open with a retractor positioned
to elevate the wall of the cavity adjacent to the patient's left
side. The retractor may be a balloon retractor, see for example
Moll U.S. Pat. No. 5,309,896 and Bonutti U.S. Pat. Nos. 5,331,975;
5,163,949; 6,277,136; 6,171,236; and 5,888,196. The peritoneum is
dissected away from the abdominal wall in first a lateral and then
a posterior direction until the spine is exposed. Under endoscopic
visualization the iliopsoas muscle is dissected or retracted to
facilitate disc repair.
[0014] Alternatively, dissection of the peritoneum can be
accomplished using gas pressure into the preperitoneal and
retroperitoneal space, thereby expanding the space and dissecting
the peritoneal lining from the abdominal wall while relocating the
peritoneal lining toward the midline of the abdomen. Access devices
that may be used to gain minimally invasive access to the spine in
several of the foregoing surgical approaches to the spine include
expanding cannula structures such as Dubrul U.S. Pat. Nos.
5,183,464 and 5,431,676, Bonutti U.S. Pat. Nos. 5,674,240 and
5,320,611, and Davison U.S. Pat. Nos. 6,652,553 and 6,187,000.
[0015] Laparoscopic Approach It is also known to approach the
lumbar spine anteriorly using a laparoscopic approach. See, for
example, Green U.S. Pat. Nos. 5,755,732 and 5,620.458. Techniques
for laparoscopic placement of spinal fusion cages are shown and
described in Kuslich U.S. Pat. No. 5,700,291 and Castro U.S. Pat.
No. 6,004,326. Implementing the laparoscopic approach requires that
one or more laparoscopic access devices, commonly referred to as
trocars (see for example Moll U.S. Pat. Nos. 4,601,710 and
4,654,030) be introduced into the abdominal cavity and that the
cavity be insufflated to create working space. A laparoscope is
inserted through one of the trocar ports to provide visualization
of the abdominal cavity and surgical instruments may be introduced
either through another trocar port or through a working channel of
the laparoscope to dissect, manipulate and retract tissue to gain
access to the posterior wall of the abdomen adjacent to the spine.
Retractors, including balloon retractors, may be used to retract
organs and tissue to maintain a clear working path. Care is taken
to avoid damage to the major blood vessels, the aorta and femoral
arteries, and the posterior wall of the peritoneum is opened to
access the desired spinal vertebral body or disc segment.
[0016] C. Imaging Techniques
[0017] A variety of tools exist to assist the surgeon in assuring
the desired access and treatment are achieved without compromising
or adversely affecting adjacent healthy tissue. Treatment of the
spine is usually planned based on CT or MR scans and fluoroscopy is
commonly used during surgery to assure proper positioning and
placement of surgical tools and devices. Image guided spinal
surgery has been proposed and is contemplated for use with the
surgical treatments proposed herein. See, for example, Cosman U.S.
Pat. Nos. 5,662,111; 5,848,967; 6,275,725; 6,351,661; 6,006,126;
6,405,072; Bucholz U.S. Pat. Nos. 5,871,445; 5,891,034; 5,851,183;
and Heilbrun U.S. Pat. Nos. 5,836,954 and 5,603,318. The position
of instruments typically is detected using a camera and markers on
the surgical tool, and an image of the working portion of the
instrument is super-imposed upon a pre-operative image, such as a
CT, MRI or ultrasound image to show the surgeon where the working
instrument is located relative to anatomical landmarks and the
tissue to be treated. As imaging techniques and equipment improve,
it is contemplated that image guided surgery will evolve to using
real time intraoperative images and that the position of the
surgical instrument will be shown relative to these real-time
intra-operative images in addition to or in place of pre-operative
images.
[0018] D. Adhesives and Other Repair Materials.
[0019] Numerous patents describe previous approaches to disc
repair. These include U.S. Pat. No. 6,332,894, Stalcup et al.,
which describes an orthopedic implant for implanting between
adjacent vertebrae comprising an annular bag and a curable polymer
and hard particulate with the bag. The polymer is cured after
implantation to make it harder and to fuse the hard particulate
into a single mass. U.S. Pat. No. 6,264,659, Ross et al., describes
a process of injecting a thermoplastic material within an annulus
fibrosis of a selected intervertebral disk. U.S. Pat. No.
6,127,597, Beyar et al., describes a solid phase formation device
for orthopedic application. The expandable device includes a
material that polymerizes after implantation. U.S. Pat. No.
6,419,706, Graf, describes a disc prosthesis comprising a preformed
polymer core surrounded by a rigid material coating. U.S. Pat. No.
6,569,442, Gan et al., describes a polymer foam prepared outside
the body for intervertebral disc reformation.
[0020] U.S. Pat. No. 6,022,376, Assell et al., describes a
capsule-shaped prosthetic spinal disc nucleus for implantation into
a human intradiscal space, made of a substantially inelastic
constraining jacket surrounding a pre-formed amorphous polymer
core. U.S. Pat. No. 6,132,465, Ray et al., describes a device
similar to the device described in U.S. Pat. No. 6,022,376 with
certain shape modifications. U.S. Pat. No. 6,306,177, Felt et al.,
describes an in situ polymerizing fluid used in tissue repair in
the absence of a constraining structure, such as a balloon. The
polymerizing materials comprise a quasi-prepolymer component and a
curative component containing chain extenders, catalysts and the
like. U.S. Pat. No. 4,743,632, Marinovic, discloses the use of a
two-part adhesive for use in surgery, where a diisocyanate material
is mixed with a polyamine or similar material to produce an in situ
cure. Preferred materials are described in our U.S. Pat. No.
6,254,327, and our pending applications US 2003-0135238 and
US-2004-0068078.
[0021] E. Other references providing background information. These
include U.S. Pat. Nos. Re. 33,258 (Onik et al.), 4,573,448
(Kambin), 5,192,326 (Bao et al.), 5,195,541 (Obenchain), 5,197,971
(Bonutti), 5,285,795 (Ryan et al.), 5,313,962 (Obenchain),
5,514,153 (Bonutti), 5,697,889 (Slotman et al.), 5,755,732 (Green
et al.), 5,772,661 (Michelson), 5,824,093 (Ray et al.), 5,928,242
(Kuslich et al.), 6,004,326 (Castro et al.), 6.187,048 (Milner et
al.), 6,226,548 (Foley et al.), 6,416,465 (Brau), WO 01/32100, and
FR 2 639 823.
SUMMARY OF THE INVENTION
[0022] None of the techniques or devices described above are
entirely satisfactory for providing percutaneous or open therapy to
damaged spinal discs.
[0023] Accordingly, it is one aspect of the present invention to
treat disc abnormalities at locations previously not accessible via
standard percutaneous approaches and without substantial
destruction to the disc. The treatment involves delivery of an in
situ polymerizing tissue adhesive into the affected areas of the
disc to seal openings in the annulus, to strengthen the annulus,
particularly by intra-annular injection of adhesive, and to couple
tissues to each other and/or to prosthetics to stabilize and
strengthen the disc, or to form a nuclear prosthetic in situ. The
improved techniques are particularly important at the posterior
lateral and the posterior medial regions of the inner wall of the
annulus fibrosus, and adjacent areas of the nucleus, which are
poorly accessible with present techniques. The tissue adhesive is
characterized in being hydrophilic, self-crosslinking in vivo, and
tissue adherent. The invention also comprises suitable devices for
administration of the adhesive.
[0024] The present invention discloses techniques for modifying the
disc annulus and/or nucleus to restore nuclear integrity. The
techniques do not involve creating a large defect in the disc
capsule. The present invention provides open and minimally invasive
surgical methods to treat disc abnormalities at locations
previously not accessible via percutaneous approaches, and without
substantial destruction of the disc and/or surrounding tissue. The
treatment entails delivery of in-situ polymerizing substances to
select locations within the disc, particularly including delivery
to the location of an annular fissure. More particularly, the
surgical methods disclosed herein involve delivering an in-situ
polymerizing fluid to repair the annulus and/or nucleus, or to
localize spinal prosthetics including nucleus replacement
prosthetics.
[0025] In addition, the invention provides a surgical method that
delivers tissue adhesive to the inner wall of the annulus fibrosus
to provide localized repair at the site of an annular fissure.
Included are surgical methods for clearing, shaping or cutting
nuclear material in order to repair an annular fissure at such a
location. Advantageously, the treatments may involve delivery of an
in-situ polymerizing tissue adhesive in such a manner that the
adhesive couples to and becomes intimately involved with the
fibrous structure of the annulus fibrosis. This is particularly
significant with respect to the repair of an annular fissure or
fixation of an implant structure within the disc nucleus. In a
preferred embodiment, the tissue adhesive for this procedure and
others is a single-part adhesive, which can be administered to
tissue without addition of other components.
[0026] The implant structure may comprise any suitable implant
grade material, including metal, for example but not limited to
titanium, cobalt, chromium, aluminum, nickel, stainless steel,
nitinol, and alloys and mixtures; plastics and polymers, for
example but not limited to PEEK, polylactide, polyglyclolide,
polycaprolactone, polycarbonate, polyester, polyacrylate,
polyalkylene, polyurethane, polyphenolic, and blends and copolymers
thereof, and other materials, for example but not limited to
graphite, ceramics including particulate ceramic fillers,
gel-forming materials, and combinations of materials. It is also
contemplated that the implant may be formed of the same material as
the single-part adhesive. The adhesive can be delivered to seal a
fissure in the annulus or to close an opening created to access the
nucleus. The adhesive may be introduced to the nucleus after
insertion of a nucleus replacement to surround and bind to the
implant and form a strong bond to the surrounding annular fibers to
hold the implant in place within the disc nucleus. The tissue
adhesive may also be used to bond a prosthetic disc replacement in
place. Various excipients and additives can be comprised in the
implant, such as plasticizers, antioxidants, emulsifiers,
colorants, fillers, radioopacifiers, coatings, and similar
materials approved for in vivo medical implantation.
[0027] In a further embodiment, it is contemplated that the in-situ
curing tissue adhesive may be introduced into the nucleus (which
may be previously evacuated by nucleotomy) to form a nucleus
implant in-situ. Additional tissue adhesive may be introduced at
the same time or subsequent to curing of the initial insertion of
material to bind the in-situ formed implant to the surrounding
annulus. Advantageously, the methods and devices disclosed herein
provide access to all regions of the inner wall of the annulus
fibrosis to deliver tissue adhesive to the interior nucleus space.
Advantageously, the methods and devices disclosed herein provide
access to the difficult-to-reach posterior, posterior lateral and
posterior medial regions of the inner wall of the annulus.
[0028] The proposed methods generally involve the steps of: [0029]
1. Accessing a desired portion of spinal disc region by known
surgical techniques, preferably in a minimally invasive manner such
as a percutaneous posterior-lateral, retroperitoneal, or anterior
laparoscopic method. The surgical approach selected may vary
depending upon the portion of the spinal disc segment to be
treated. [0030] 2. Optionally, removing tissue, preferably
minimizing removal of healthy tissue while removing diseased or
degenerated tissue (e.g. removing bulging portions of the annulus
fibrosis, or nucleus pulposis, removal of osteophytes, etc.) [0031]
3. Delivering an in-situ polymerizing tissue adhesive to perform a
desired repair, which may included repairs to any or all of the
exterior of the annulus, the interior wall of the annulus, or
within the wall of the annulus fibrosis, augmenting or replacing
all or a portion of the disc nucleus (which may have previously
been removed during the same or prior surgery) with the in-situ
polymerizing fluid, or securing a spinal disc replacement implant,
disc nucleus replacement or other spinal implant in place. [0032]
4. If the disc annulus has been compromised during surgery and is
to be closed as part of the surgical procedure, closing the opening
in the disc nucleus. Preferably, the in-situ polymerizing fluid is
used to close the opening in the disc annulus. [0033] 5. Closing
any openings created to gain access to the spine.
[0034] The present invention further provides methods for
manipulating a disc tissue with herniation, or with a fissure or
tear in an intervertebral disc, the disc having a nucleus pulposus
and an annulus fibrosus, the annulus having an inner wall of the
annulus fibrosus. The methods employ a variety of externally
guidable cutting and delamination devices to repair the disc. The
procedure is performed with one or more cutting, shaping, and/or
delivery devices passed through a trocar having a distal end, a
proximal end, a longitudinal axis, and an intradiscal section at
the catheter's distal end on which there is at least one functional
element. A series of cannulae of gradually increasing diameter may
be used to provide a small initial entry diameter gradually
increased to the desired diameter to access the spine.
Alternatively, an expanding cannula device such as disclosed in the
previously mentioned Dubrul, Bonutti or Davison patents may be used
to provide minimal entry opening size increased to a larger desired
diameter access the spine.
[0035] A variety of surgical approaches such as the posterior
lateral and retroperitoneal approaches described above can be used.
One method employs a wire, ribbon or catheter to be advanced
through the annulus and into the nucleus pulposus and around an
inner wall of an annulus fibrosus by applying a force to the
proximal end. In the case where the annulus is open, the applied
force is insufficient for the intradiscal section to puncture the
annulus fibrosus. In the case where the annulus is not open, the
intradiscal section of the device may be substantially sharper to
provide a first passage through the annulus and into the nucleus.
The functional element, which may simply be a hollow needle, is
positioned at a selected location in the disc by advancing or
retracting the device and optionally twisting the proximal end of
the device. The catheter and/or the needle may be steerable in
order to deliver the tissue adhesive to a particular location
within the disc or annulus. The procedure allows the administration
of tissue adhesive to treat annular fissures, to fill the nucleus
to form an implant in-situ, or to bind a pre-formed implant in
place within the disc nucleus.
[0036] A method of treating an intervertebral tissue comprises the
steps of placing a catheter adjacent to the defect and delivering
tissue adhesive sufficient to strengthen and bond collagen and to
seal the fissure. This operation may include filling portions of
the nucleus. Alternatively, the fissure may be sealed and
subsequently the annulus filled and pressurized allowing for the
injected polymer to solidify before removing the needle.
[0037] In addition to the method, there is provided a tissue
adhesive sufficient to provide the therapeutic effect of
strengthening the intervertebral space and preventing extrusion of
the disc or a prosthetic. The preferred adhesive is a
single-component polyisocyanate based adhesive as described in U.S.
Pat. Nos. 6,254,327, 6,296,607, and co-pending U.S. provisional
patent application Ser. No. 60/557,314, which is incorporated
herein by reference in its entirety. In one aspect, the present
invention provides a minimally invasive method and device for
treating fissures of discs at selected locations within the
disc.
[0038] Another aspect of the invention is to provide an apparatus
that delivers tissue adhesive to the inner wall of the annulus
fibrosus to provide localized repair at the site of an annular
fissure.
[0039] Another aspect of the invention is to provide a device that
has a distal end that is inserted into the disc and accesses the
posterior, posterior lateral and the posterior medial regions of
the inner wall of the annulus fibrosus in order to repair an
annular fissure at such a location.
[0040] Another aspect of the invention is to provide a minimally
invasive method and device for treating discs at selected locations
within the annulus fibrosus. In particular it relates to fixing the
fibers of the annulus in a preferred orientation and providing
increased rigidity to the annulus by increasing its volume with a
polymerizing fluid.
[0041] Another aspect of the invention is to provide an apparatus
which delivers tissue adhesive within the wall of the annulus
fibrosus to provide increased support and space between vertebral
bodies.
[0042] Another aspect of the invention is to provide a device that
has a distal end that is inserted into the wall of the annulus and
accesses the posterior, posterior lateral and the posterior medial
regions of the annulus fibrosus in order to repair an annulus at
such a location.
[0043] Another aspect of the invention is to provide a minimally
invasive method and device for fixing, fitting, and augmenting the
size of prosthetic nucleus replacement devices either during
implantation or at any time post implantation.
[0044] Another aspect of the invention is to provide a new method
of implanting a nucleus prosthetic that includes closing the hole
created in the annulus by implantation of the prosthetic.
[0045] Another aspect of the invention is to provide an apparatus
which delivers tissue adhesive to the inner wall of the annulus
fibrosus to localize and fit a nucleus prosthetic.
[0046] Another aspect of the invention is to provide a device that
has a distal end that is inserted into the disc and accesses the
posterior, posterior lateral and the posterior medial regions of
the inner wall of the annulus fibrosus in order to localize and fit
a nucleus prosthetic.
[0047] Another aspect of the invention is to provide a method of
treating an intervertebral tissue comprises the steps of placing a
catheter adjacent to the tissue, or an adjacent prosthetic, and
delivering tissue adhesive sufficient to strengthen and bond
collagen and other local tissues to repair a fissure or hole, to
strengthen an annulus, and to localize and fit a nucleus
prosthetic. These operations may include filling portions of a
nucleus cavity, or of a fissure or other deficit, under pressure.
Alternatively or in addition, filling operations may be facilitated
by unloading the particular region of the spine to enhance filling
of an intervertebral space.
[0048] Another aspect of the invention is to provide a tissue
adhesive sufficient to provide the therapeutic effect of
strengthening the intervertebral space and preventing extrusion of
the disc. The tissue adhesive may be of a wide variety of types,
but preferably is a one part adhesive that cures in situ, and which
is a preferred embodiment is a hydrophilic, substantially water
soluble isocyanate derivative of a polyol or polyols.
[0049] These and other aspects of the invention have been
accomplished by the present invention which provides methods and
systems for manipulating annulus tissue with and without a fissure
or tear, and native or prosthetic nucleus tissue, in an
intervertebral disc, the disc having a nucleus pulposus and an
annulus fibrosus, the annulus having an inner wall of the annulus
fibrosus.
BRIEF DESCRIPTION OF THE FIGURES
[0050] The invention is understood by reference to the following
figures.
[0051] FIG. 1(a) is a superior cross sectional anatomical view of a
cervical disc and vertebra. FIG. 1(b) is a lateral anatomical view
of a portion of a lumbar spine. FIG. 1(c) is a posterior-lateral
anatomical view of two lumbar vertebrae and illustration of the
triangular working zone. FIG. 1(d) is a superior cross sectional
view of the required posterior lateral approach. FIG. 1e is a side
view and FIG. 1f is a perspective view of a disc and some critical
measurements.
[0052] FIG. 2 is a plan view of an introducer and an instrument of
the invention in which solid lines illustrate the position of the
instrument in the absence of bending forces and dotted lines
indicate the position of the distal portion of the instruments
would assume under bending forces applied to the intradiscal
section of the instrument.
[0053] FIG. 3 is a flow diagram of a procedure for modifying the
disc nucleus;
[0054] FIGS. 4a, b is a plan view of an approach to the disc
nucleus using a hollow needle to place a guidewire; FIG. 4c is a
plan view of a trocar obdurator approaching the disc over the
guidewire;
[0055] FIG. 5 is a cross-section view of a cannula with an annulus
punch placed therethrough;
[0056] FIG. 6 illustrates the annulus punch penetrating the
annulus;
[0057] FIGS. 7A-7D are illustrations of cutting wire placement
within the disc;
[0058] FIG. 8 is a partially sectioned perspective view of a disc
with a delivery catheter for delivery of adhesive to the disc
nucleus;
[0059] FIG. 9 illustrates an alternative approach of creating
multiple channels in the disc nucleus and delivering adhesive to
the channels;
[0060] FIG. 10 illustrates a nucleus bore.
[0061] FIG. 11 illustrates an alternative approach to disc nucleus
removal;
[0062] FIG. 12 illustrates blunt dissection of the disc nucleus
from the annulus;
[0063] FIG. 13 illustrates augmentation of the annulus with
adhesive;
[0064] FIG. 14 illustrates an alternative approach to annulus
augmentation using a wire or ribbon to delineate layers of the
annulus to create space to facilitate adhesive placement;
[0065] FIG. 15 is a cross-section view of a disc illustrating a
needle advanced through the annulus wall;
[0066] FIG. 16 is a cross-section view illustrating catheter
delivery of the adhesive;
[0067] FIG. 17 illustrates a two-step technique wherein a first
application of adhesive to the disc nucleus is allowed to
substantially or completely polymerize, and a second application of
adhesive expands and fills the first material to expand and fill
the disc space;
[0068] FIG. 18 illustrates the use of jacks or wedges to increase
disc height prior to or during delivery of the adhesive;
[0069] FIG. 19 illustrates delivery of a disc nucleus implant and
adhesive securement of the implant in the disc;
[0070] FIG. 20 illustrates in cross-section the repair of an
annulus opening by gluing a mesh over the opening;
[0071] FIG. 21 illustrates dissection and repair of an annulus
defect without treatment of the disc nucleus;
[0072] FIG. 22 illustrates repair of a fissure in the annulus.
DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS
[0073] The present invention provides methods and apparatus for
treating intervertebral disc disorders by delivering a tissue
adhesive to the spinal disc space, preferably within the disc
nucleus to repair a fissure, particularly a fissure of the annulus
fibrosis, which may or may not be accompanied with contained or
escaped extrusions. The adhesive may also be used to create a disc
nucleus implant in-situ, or bond a pre-formed disc nucleus implant
in place. Preferably, the methods and devices are used to deliver a
single-part in-situ polymerizing tissue adhesive to accomplish the
desired surgical results.
[0074] In one aspect, the invention comprises coupling a
tissue-polymerizing agent with a guidable intervertebral disc
apparatus for accessing and delivering an in-situ polymerizing
agent at a location in an intervertebral disc having a nucleus
pulposus and an annulus fibrosus, the annulus having an inner wall.
The invention is distinguished from conventional percutaneous
interventions in not being reliant on reference measurements and
selection of appropriate instrument sizes. Such conventional
instruments are typically designed for one disc size. Additionally,
in some embodiments the present invention can be used with any of a
variety of insertional apparatus to provide proximity to the disc,
such as insertional apparatus known in the art as "introducers". An
introducer has an internal lumen with a distal opening at a
terminus of the introducer to allow insertion/manipulation of the
operational parts into the interior of a disc.
[0075] The elements of the invention function in combination to
modify or change certain features of the disc anatomy. For purposes
of this specification, the inner wall of the annulus fibrosus can
include the young wall comprised primarily of fibrous material as
well as the transition zone, which includes both fibrous material
and amorphous colloidal gels.
[0076] To appreciate the situation in which repairs to spinal discs
is attempted, the anatomy is illustrated in FIGS. 1a and 1b, which
illustrate a cross sectional view of the anatomy of a vertebra and
associated disc and a lateral view of a portion of a lumbar and
thoracic spine, respectively. (A more detailed and
three-dimensional view of the parts of the vertebrae and disc than
can be provided here can be found in good anatomy references and
textbooks.) Structures of a typical cervical vertebra (superior
aspect) are shown in FIG. 1(a): 704--lamina; 706--spinal cord;
708--dorsal root of spinal nerve; 714--ventral root of spinal
nerve; 718--intervertebral disc; 720--nucleus pulposus;
722--annulus fibrosus; 724--anterior longitudinal ligament;
726--vertebral body; 728--pedicle; 730--vertebral artery;
732--vertebral veins; 734--superior articular facet; 736--posterior
lateral portion of the annulus; 738--posterior medial portion of
the annulus; 740--vertebral plate, and 742--spinous process. In
FIG. 1(a), one side of the intervertebral disc 718 is not shown so
that the anterior vertebral body 726 can be seen. FIG. 1(b) is a
lateral aspect of the lower portion of a typical spinal column
showing the entire lumbar region and part of the thoracic region
and displaying the following structures: 718--intervertebral disc;
726--vertebral body; 742--spinous process; 770--inferior vertebral
notch; 710--spinal nerve; 774--superior articular process;
776--lumbar curvature; and 780--sacrum. FIG. 1c shows a
posterior-lateral anatomical view of two lumbar vertebrae,
including the pedicle 728, the spinal nerve 710, the annulus
fibrosus 722, the vertebral body 716, and the spinous process
742.
[0077] The presence of the spinal cord 706 and the posterior
portion of the vertebral body, including the spinous process 742,
and superior articular 774 and inferior articular processes
(inferior is not visible; behind superior process 774), prohibit
introduction of a needle or trocar from a directly posterior
position. This is important because it is most frequently the
posterior disc wall that is the site of symptomatic annulus tears
and disc protrusions/extrusions that compress or irritate spinal
nerves in degenerative disc syndromes. The inferior articular
process, along with the pedicle 728 and the lumbar spinal nerve
710, form a small "triangular" window through which introduction
can be achieved from the posterior lateral approach. It is well
known that percutaneous access to the disc is achieved by placing
an introducer into the disc from this posterior lateral approach,
but the triangular window does not allow much room to maneuver.
Once the introducer pierces the tough annulus fibrosus, the
introducer is fixed at two points along its length and is
restricted in movement. Hence, this common approach allows only
restricted access to portions of the nucleus pulposus.
Specifically, the posterior half of the nucleus or the posterior
wall of the disc is inaccessible.
[0078] FIG. 1d illustrates the posterior lateral approach through
the triangle, and allows visualization of the problem. In this
illustration, there is a fissure 750 in the posterior wall of the
annulus 736, through which the nucleus 720 is bulging, thereby
exerting pressure on the spinal cord 706 or on a spinal nerve (not
illustrated). A rigid apparatus 760 inserted through the posterior
lateral region 738 of the annulus 722 can access the nucleus 720,
for example to remove it, but cannot readily treat the fissure 150,
or strengthen the posterior medial annulus 736 to prevent
recurrence. Although a nuclear prosthetic can be delivered into the
space formerly occupied by the nucleus, it will not be attached to
the surrounding annulus 722, nor will the fissure 750 be
closed.
[0079] FIGS. 1e and 1f are schematic views of the anatomy of the
disc itself, and of key orientations in it. As used herein, the
terms "disc plane", oblique plane" and "cephalo-caudal plane" refer
to orientations of a catheter within the intervertebral disc.
Referring to FIG. 1e, a disc plane 630 of the intervertebral disc
629 is generally a plane of some thickness 27 within the nucleus
pulposus 720. The disc plane 630 is orthogonal to the axis 632
formed by the spinal column. An oblique plane 631 is a plane which
is tilted in orientation relative to axial plane 630. However, when
the oblique plane 631 is tilted 90 degrees with respect to plane
632, such a plane 631 would be substantially vertical in a standing
human and is referred to as a cephalo-caudal plane. Disc plane 630
has a thickness no greater than the thickness of the intervertebral
disc, preferably a thickness no greater than 75% of the thickness
of the intervertebral disc, and more preferably a thickness no
greater than 50% of a thickness of an intervertebral disc. In a
healthy disc, the spinal axis 632 is orthogonal to disc plane 630,
and the angle between plane 630 and plane 631 is zero. One aspect
of the present invention is the alteration of the thickness 627 of
disc 629 to achieve a zero angle.
[0080] Nucleus replacement devices are intended to be used where
the annulus and vertebral endplates remain intact, and the
prosthesis is implanted into the nucleus cavity through a window
formed in the annulus. Insertion of the prosthetic through a window
in the annulus requires that the prosthetic be smaller than the
nucleus cavity. Current devices expand when implanted to a
relatively large post-implant size that is as much as 3 times the
original implantation volume. The use of a reduced size nucleus
prosthesis means that the prosthesis can move within the nucleus
cavity until the prosthesis reaches its target size, which can
require as much as three days to achieve. In some cases the
prosthesis explants through the annulus opening. Even when the
opening is closed with sutures the implant can still push through
the annulus opening. Additionally, a reduced size implant generally
means the implant must be stiffer than the optimal flexibility the
implant is intended to achieve once enlarged. This further reduces
the size of the implant so that it will fit through the annulus
window. The result is a compromise between ease of implantation and
final state implant flexural characteristics. This situation can be
remedied using an in situ acting surgical adhesive and bulking
agent. A variety of surgical adhesives are potentially useable in
the invention, but a preferred adhesive is described here.
Surgical Adhesives and Bulking Agents
[0081] Turning now to the functional aspects of the invention, the
two principal material components of the invention are a suitable
tissue adhesive and bulking agent ("adhesive"), and a suitable
apparatus ("injector") for depositing the adhesive. The invention
further comprises improved methods for use of an adhesive to repair
defects in a disc, including repair of the annulus, optionally
accompanied by immobilization of a prosthesis and/or filling of a
nuclear space. Regarding the adhesive or bulking agent, a liquid
material is introduced into the intervertebral space to repair the
tissue and fluids contained therein. The liquid material must have
a low viscosity and be capable of delivery through a small diameter
needle, cannula or catheter, for example through a typical catheter
having a diameter ranging from 16G to 25G (but smaller diameter
devices can be used if viscosity is sufficiently low.) Low
viscosity is important in three respects: 1) ease of delivery, 2)
prevention of delayed pressure transference from source to the
target tissue site, and 3) permits sensing of resistance feedback
by the operator to determine appropriate delivery volumes.
[0082] The preferred material of the present invention is a single
component, self-curing adhesive that polymerizes in-situ forming
internal cross links as well as bonds to surrounding tissue and
bone. The polymerization of the preferred material is initiated
either by aqueous fluids present in the tissue or by addition of
physiological saline or other medicinal solution. The
polymerization of these adhesives preferably does not require the
addition of cross linkers, catalysts, chain extenders, or
complementary components of an adhesive. Preferably, cross linking
and tissue bonding is mediated either by aqueous fluids present in
the tissue, or by premixing of the adhesive with physiological
saline or other medicinal saline solution at the time of
administration. The polymerization time of preferred adhesives is
variable, and preferably is in the range of about 30 seconds to 30
minutes or more, depending on the application. Preferred materials
are described in our U.S. Pat. No. 6,254,327, and our pending
applications US 2003-0135238 and US 2004-0068078, each of which is
hereby incorporated by reference (where permitted).
[0083] Polymerization time can be adjusted by selection of
properties and components of the tissue adhesive. Principally, the
material is a liquid comprising a polyisocyanate-capped polyol,
typically macromolecular in size, having a molecular weight of
about 1000 Daltons or more, more typically at least about 2000
Daltons, and yet more typically in a range of about 3000 D to about
10,000 D, depending on application. Higher molecular weight
macromers may be of use in adhesives having great pliability (and
lower tensile strength). The adhesive also typically comprises a
certain amount of low-molecular weight polyisocyanate, for example
with a molecular weight less than about 1000 D. This may comprise
the polyisocyanate used to cap the polyols. The capped polyol is
multifunctional, and typically at least partially trifunctional or
higher. The polyol may be any of various biocompatible substances
such as polyethylene oxide, polypropylene oxide, polyethylene
glycol, and copolymers of these. A preferred polyol has about 10%
to about 30% by weight propylene oxide subunits, and the rest
ethylene oxide. The polyisocyanate is typically difunctional. Fast
reacting formulations use an aromatic diisocyanate such as toluene
diisocyanate. Slow reacting formulations use an aliphatic
diisocyanate such as isophorone diisocyanate. Alternatively, the
polymerization time can be adjusted by selection of appropriate
molecular weight polyols. The higher molecular weight polyols
produce lower viscosity capped reaction products and faster
reacting solutions.
[0084] The cure times achieved using the approaches described above
depend, in part, on controlling one or more of the rate of water
diffusion into the prepolymer, the rate of isocyanate to amine
conversion, and the activity of the isocyanate-functionalized ends.
There are various additions to the prepolymer that can be made at
the time of application to speed prepolymer curing. For example,
when water is added to the prepolymer just before application, the
cure time dependence on water diffusion is reduced. Generally,
addition of water in volumetric ratios of approximately 50%
maximally reduces cure time. When additional water is added, such
as 80 or more % by volume, the cure time increases from its fastest
mixed cure time because the polymer density decreases. Similarly,
when using higher concentrations of prepolymer, such at 80% or more
by volume, the cure time increases from its fastest cure time
because the water availability decreases. However, all mixtures
with water, from 1% up to about 95% by volume, cure faster than
application of prepolymer placed directly on tissue. It is
sometimes desirable to lightly irrigate the location with water
after pure prepolymer has been applied to tissue.
[0085] The first action of water with the prepolymer is to convert
some of the active isocyanate ends on the isocyanate capped polyol
and some of the active isocyanate ends on the free isocyanate to
amine groups. Amine groups react with other isocyanate groups to
cause rapid chain extension and eventual crosslinking. Therefore,
reduced cure times can also be achieved by substituting some or all
of the water admixture with aqueous amines.
[0086] The preferred material is an aromatic isocyanate made by end
capping a deionized, dried polyalkylene diol with toluene
diisocyanate(TDI), and then reacting the end-capped diol with a
deionized dried triol. The preferred diol is a polyethylene
glycol/polypropylene glycol co-polymer (random, block or graft),
with EO (ethylene oxide) and PO (propylene oxide) in weight ratios
ranging from about 95:5 to about 25:75, and more preferably about
75% EO and 25% PO. The preferred triol is trimethylol propane
(TMP). The preferred composition is the reaction product of from
about 25% to 35% TDI, from about 65% to 75% diol (75% EO: 25% PO)
and from about 1% to about 8% TMP. Most preferably, the composition
is the reaction product of about 30% TDI, about 70% of the 75:25
diol, and about 1% to about 2% TMP.
[0087] These polymer mixtures have the added advantage of being
water-soluble. Their water solubility enables them to be injected
into tissue to polymerize the tissue; or, alternatively to solidify
as gels to stabilize tissue or structures. The material acts as a
self-sealing fluid when injected into body cavities.
[0088] Isocyanate-capped polyols, while preferred, are not the sole
adhesives suitable for use in the invention. An adhesive for use in
the invention is preferably hydrophilic in character, and more
preferably is water-soluble before being crosslinked. This
hydrophilicity enable the adhesive to be injected into tissue to
polymerize in contact with, and bond to, the tissue, as adhesive
and/or as local bulking agent to fill gaps or fissures, or to
stabilize implants. The adhesive acts as a self-sealing fluid when
injected into cavities or gaps. Once cured in situ, the hydrophilic
adhesive will absorb fluid from the tissue, forming a structure
that will be at least somewhat gel-like in character. The cured
adhesive will swell to a controlled extent, exerting a controlled
amount of local pressure. The tensile properties of the cured
adhesive can be adjusted so that the adhesive, like the native
tissues of the annulus or of the nucleus, yields under pressure
while exerting a restorative force on the surrounding structures.
Hence, the adhesive-tissue composite tends to return to its
original shape and location after movement of the spine. These
properties can be controlled by the composition of the adhesive, or
by providing a controlled degree of dilution with saline at the
time of administration. This is in contrast with rigid materials,
which tend to fracture rather than yield, and to flowable media,
which have no tendency to return to their original shape after
relaxation of stress. In particular, hydrophobic adhesives tend to
become rigid, favoring fracture of the cured adhesive at the
surface of the tissue or implant. They also tend not to bond to
tissue, which is highly hydrophilic.
[0089] The unpolymerized adhesive is preferably polymeric in
nature, as opposed to being a low molecular weight monomer before
curing, such as a cyanoacrylate. A number of known polymers are
potentially useful in formation of suitable adhesives. The polymers
are preferably hydrophilic, for example, sufficiently hydrophilic
to swell in water. A suitable range of swelling can be, at
atmospheric pressure, between from 5% to about 100%, and more
typically is from about 10% to about 50%. More preferably, the
prepolymers are sufficiently hydrophilic to have substantial
solubility in water, such as, for instance, 1 g/l or more,
preferably 10 g/l or more, optionally 100 g/l or more. The
molecular weight of the prepolymers is not critical. In the present
application, number-average MW, or alternatively the MW number on
the label of a commercial product, is in the range extending from
about 500 D, more preferably about 1000, most preferably about
2000, up to 100,000 D, more preferably 50,000 D, most preferably
25,000 D. The molecular weight will vary by application and with
polymer backbone. It will generally be as low as feasible, to
minimize viscosity, while being sufficiently high to provide the
desired materials properties, such as strength of adherence to
tissue, or adequate tensile strength. However, higher viscosities
may be desirable in some cases, especially when curing time is
longer. The polymers are preferably selected from those approved
for in-vivo medical application. The polymers may be stable in the
body, or may degrade in the body to smaller, excretable molecules
("degradable"). A wide variety of linkages are known to be unstable
in the body. These include, without limitation, esters of hydroxy
acids, particularly alpha and beta hydroxy carboxylic acids; esters
of alpha and beta amino acids; carboxylic acid anhydrides;
phosphorous esters; and certain types of urethane linkages.
Generally, it is preferred that the adhesive be stable in the body
for prolonged periods, as the fibrous materials of the annulus have
very limited self-repair capabilities, and the nucleus has
virtually none. However, if methods are found to enhance natural
biological repair of the nucleus or annulus, then degradable
adhesives or fillers could be preferred.
[0090] The polymers also have reactive groups covalently attached
to them, or part of the backbone. The reactive groups are suitable
for reaction with tissue, and for crosslinking in the presence of
water or components of bodily fluids, for example water and
protein. Suitable groups include isocyanate, isothiocyanate,
anhydrides and cyclic imines (e.g., N-hydroxy succinimide,
maleimide, maleic anhydride), sulfhydryl, phenolic, polyphenolic,
and polyhydroxyl aromatic, and acrylic or lower alkyl acrylic acids
or esters. Such reactive groups are most commonly bonded to a
preformed polymer through suitable linking groups in the polymer.
Commonly found linking groups include, without limitation, amines,
hydroxyls, sulfhydryls, double bonds, carboxyls, aldehydes, and
ketone groups. Of these groups, aliphatic hydroxyls are among the
most widely used.
[0091] Thus, suitable base polymers include poly(alkyl)acrylic
acids and polyhydroxyalkyl acrylates, polysaccharides, proteins,
polyols, including polyetherpolyols, polyvinyl alcohol, and
polyvinylpyrrolidone, and these same structures with amine or
sulfur equivalents, such as polyethyleneimine, aminosugar polymers,
polyalkylamine substituted polyethers, and others. Any of these
polymers can be substituted with two or three reactive groups, as
is required to form a crosslinkable polymer. When there are many
substitutable linking groups, as with polysaccharides, only a few
of the substitutable groups (here, mostly hydroxyls) should be
substituted, and the derivatized polymer will have a somewhat
random substitution. Preferably, the hydrophilic polymer will have
only a few substitutable linking groups. Polyether polyols grown on
glycol or amine starters will typically have reactive groups only
at the end of the polyether chains, allowing for detailed control
of stoichiometry. Such polymers are preferred. Most preferably, the
base polymer is a polymer of ethylene glycol, or a copolymer of
ethylene glycol with one or more of propylene glycol, butylene
glycol, trimethylene glycol, tetramethylene glycol, and isomers
thereof, wherein the ratio of ethylene glycol to the higher
alkanediol in the polymer is sufficient to provide substantial
water solubility at room or body temperature. Such polymer
substrates can be synthesized by known methods. More typically,
preformed polyetherpolyols are purchased, optionally in a
prequalified medical grade, from any of numerous catalogs or
manufacturers.
[0092] As noted above, the preferred reactive material comprises a
polyisocyanate-capped polymeric polyol and a small amount of free
poly isocyanate. Such materials and their synthesis are described
in detail in U.S. Pat. No. 6,524,327. The small amount of excess
polyisocyanate, typically of molecular weight less than about 1000
Daltons, maximizes the reactivity of the polyols, and by directly
and rapidly reacting with tissue, promotes bonding of the adhesive
to tissue. Typically the small isocyanate contains up to about 3%
of the number of active isocyanate groups on the polymer. The
capped polyol is multifunctional, and typically is trifunctional or
tetrafunctional, or a mixture of trifunctional and/or
tetrafunctional with difunctional. The polyol is preferably at
least in part a polyether polyol as described above.
[0093] The polyisocyanate is typically difunctional, but tri- or
tetrafunctional, or star, forms of isocyanate are known and can be
useful. Branching (tri- or tetra-functionality) may be provided by
a trifunctional polymer, or by providing a tri- or tetrafunctional
low molecular weight polyol, such as glycerol, erthyritol or
isomer, or trimethylolpropane (TMP). Fast reacting formulations use
an aromatic diisocyanate such as toluene diisocyanate. Slow
reacting formulations use an aliphatic diisocyanate such as
isophorone diisocyanate. Many additional diisocyanates are
potentially useful. Some are listed in U.S. Pat. No. 6,524,327, and
these and others are found in chemical catalogs, for example from
Aldrich Chemical. Alternatively, the polymerization time can be
adjusted by selecting appropriate molecular weight polyols. The
higher molecular weight polyols produce lower viscosity capped
reaction products and slower reacting solutions. However, at any
molecular weight of the polyol(s), the reaction rate is most
significantly determined by the reactivity of the functional end
group attached to the polyol.
[0094] The adhesive preferably is liquid at room temperature (ca.
20 degrees C.) and body temperature (ca. 37 degrees C.), for ease
of administration and of mixture with additives, etc. The adhesive
preferably is stable in storage at room temperature, when protected
from moisture and light.
[0095] The reactive polymer tissue adhesive may be supplemented by
the addition, during manufacture or at the time of administration,
of ancillary materials. These may include reinforcing materials,
drugs, volume or osmotic pressure controlling materials, and
visualization aids for optical, fluoroscopic ultrasound or other
visualization of fill locations. Reinforcing materials may include
particulate materials, fibers, flocks, meshes, and other
conventionally used reinforcers. It is preferred that these be
commercial materials approved for in vivo medical use.
Visualization materials include a wide variety of materials known
in the art, such as, among others, small particles of metals or
their oxides, salts or compounds for fluoroscopy, gas-filled
particles for ultrasound, and dyes or reflecting particles for
optical techniques.
[0096] Osmotic properties can be adjusted for immediate or
long-term effects. The preferred polyether polyol isocyanates have
little ionic charge either before or after polymerization. However,
in some situations, as described below, it is desirable to have a
controlled degree of swelling in water after curing. This can be
controlled in part by the ratio of ethylene glycol to other polyols
in the formulation. It can also be adjusted by adding charged
groups to the formulation. A simple method is to add charged
polymers or charged small molecules to the adhesive at the time of
application, for example dissolved in an aqueous solution. Charged
polymers, such as polyacrylic acids, will react poorly with the
isocyanates, but will tend to be trapped in the polymerized matrix.
They will tend to increase the swelling of the cured material. In
turn, this would allow the use of higher proportions of
non-ethylene glycol monomers in the polyols. Alternatively, charge
could be introduced by addition of hydroxy carboxylic acids, such
as lactic acid, or tartaric acid, during synthesis or during
administration. Added polymers could instead be polyamines, but, to
avoid rapid polymerization, should be tertiary or quaternary amines
or other amine types that will not react with isocyanate. A method
of increasing swelling is to incorporate higher concentration of
diffusible ions, such as soluble salts--e.g., sodium chloride--into
the adhesive at the time of application. The salt will attract
water into the adhesive polymers; after polymerization, the salt
will diffuse away and the gel will remain expanded.
[0097] The reactive polymer can be adjusted in several ways to
optimize its post-cure properties for the particular situation. A
preferred method of adjustment of properties is dilution of the
polymer with water, saline, or other aqueous solution. A typical
dilution would be in the range of 5% or less (volume of saline in
liquid polymer), for formation of dense, high-tensile, low-swelling
deposits, up to about 95% (19 vol. saline/vol. polymer) for readily
swelling, highly compliant deposits or bonds. In formulation,
allowance must be made for the amount of water that will flow into
the adhesive from the tissue during reaction. This will usually be
relatively small for bulk deposits, but is of more concern for thin
adhesive layers. In thin layers, fast-curing compositions will be
preferred, such as compositions with a higher proportion of
aromatic diisocyanates. In general, dilution will reduce the
tensile strength and the modulus. The amount of dilution will tend
to be different depending on whether the modulus or tensile
strength is to match that of the annulus (higher) or the nucleus
(lower).
[0098] Various non-reactive ingredients can be added to the polymer
solution either in the prepolymer or in the aqueous solution to
alter the hydrogel mechanical properties, e.g., tensile strength,
elasticity and bubble size. Inert particulate such as tantalum
powder will result in bubble nucleation and a finer bubble size,
increase the modulus of the hydrogel, and make the hydrogel radio
opaque. Emulsifiers can be added to increase mix homogeneity,
reduce bubble size, and provide a higher elongation at break. It is
possible to use the same diol used to construct the prepolymer as
an emulsifier. Alternatively, a higher or lower molecular weight
diol may be used. The ratio of EO/PO can be altered to increased
mixability, or pure forms of EO or PO can be used. When pure EO is
used, the mixture of prepolymer and aqueous solution becomes
non-Newtonian, and tends to take on a stringy consistency, which
can further improve elasticity.
[0099] Other adjustable factors include the molecular weight of the
polymer, and its degree of branching; and its hydrophilicity, which
is a function of the particular polyol or polyols used in the
formulation. In addition, additives, as described above, can also
influence these properties.
Examples of the Polymeric Composition
[0100] The invention comprises a liquid preparation for use in
medicine, and its uses therein. The liquid preparation contains a
reactive polymer, which comprises a "base polymer" or "backbone
polymer", reactive groups on the backbone polymer, and a slight
excess of "free" (low molecular weight) polyreactive molecules. The
liquid composition is prepared by a method requiring no catalysts
and essentially no solvent. The reactive liquid polymer is
self-curing when applied to tissue, by absorption of water and
other reactive molecules from the tissue. The cured polymer is used
to seal tissue to tissue, or to devices; to apply a protective
coating to tissue; to form an implant within or upon tissue; to
deliver drugs. The cured polymer is optionally provided with
biodegradable groups, and has a controllable degree of swelling in
bodily fluids.
Backbone Polymers
[0101] The backbone polymer will comprise a polymeric segment, of
molecular weight about 500 D or more, preferably about 1000 to
about 10,000 D, optionally up to about 15 kD or 20 kD. The backbone
polymer will contain groups that can be easily derivatized
("capped") to form the final reactive group. Such groups are
preferably alcohols or amines, or optionally sulfhydryls or
phenolic groups. Examples include polymers such as a polymeric
polyol, or optionally a polymeric polyamine or polyamine/polyol.
The preferred polyols are polyether polyols, such as polyalkylene
oxides (PAOs), which may be formed of one or more species of
alkylene oxide. The PAO, when comprising more than one species of
alkylene oxide, may be a random, block or graft polymer, or a
polymer combining these modes, or a mixture of PAO polymers with
different properties. Preferred alkylene oxides are ethylene oxide
and propylene oxide. Other oxiranes may also be used, including
butylene oxide. PAOs are typically made by polymerization onto a
starter molecule, such as a low molecular weight alcohol or amine,
preferably a polyol. Starting molecules with two, three, four or
more derivatizable alcohols or other derivatizable groups are
preferred. The multi-armed PAOs obtained from such starters will
typically have one arm for each group on the starter. PAOs with
two, three or four terminal groups are preferred. Mixtures of PAOs
or other backbone polymers, having variable numbers of arms and/or
variation in other properties, are contemplated in the
invention.
[0102] Common polyols useful as starters in the present invention
are aliphatic or substituted aliphatic molecules containing a
minimum of 2 hydroxyl or other groups per molecule. Since a liquid
end product is desired, the starters are preferably of low
molecular weight containing less than 8 hydroxyl or other groups.
Suitable alcohols include, for illustration and without limitation,
adonitol, arabitol, butanediol, 1,2,3-butanetriol,
dipentaerythritol, dulcitol, erythritol, ethylene glycol, propylene
glycol, diethylene glycol, glycerol, hexanediol, iditol, mannitol,
pentaerythritol, sorbitol, sucrose, triethanolamine,
trimethylolethane, trimethylolpropane. Small molecules of similar
structures containing amines, sulfhydryls and phenols, or other
groups readily reactive with isocyanates, are also useable.
[0103] The PAO, or other backbone polymer, may optionally
incorporate non-PAO groups in a random, block or graft manner. In
particular, non-PAO groups are optionally used to provide
biodegradability and/or absorbability to the final polymer. Groups
providing biodegradability are well known. They include hydroxy
carboxylic acids, aliphatic carbonates, 1,4-dioxane-2-one
(p-dioxanone), and anhydrides. The hydroxy carboxylic acids may be
present as the acid or as a lactone or cyclic dimmer, and include,
among others, lactide and lactic acid, glycolide and glycolic acid,
epsilon-caprolactone, gamma-butyrolactone, and delta-valerolactone.
Amino acids, nucleic acids, carbohydrates and oligomers thereof can
be used to provide biodegradability, but are less preferred.
Methods for making polymers containing these groups are well known,
and include, among others reaction of lactone forms directly with
hydroxyl groups (or amine groups), condensation reactions such as
esterification driven by water removal, and reaction of activated
forms, such as acyl halides. The esterification process involves
heating the acid under reflux with the polyol until the acid and
hydroxyl groups form the desired ester links. The higher molecular
weight acids are lower in reactivity and may require a catalyst
making them less desirable.
[0104] The backbone polymers may also or in addition carry amino
groups, which can likewise be functionalized by polyisocyanates.
Thus, the diamine derivative of a polyethylene glycol could be
used. Low molecular weight segments of amine containing monomers
could be used, such as oligolysine, oligoethylene amine, or
oligochitosan. Low molecular weight linking agents, as described
below, could have hydroxyl functionality, amine functionality, or
both. Use of amines will impart charge to the polymerized matrix,
because the reaction product of an amine with an isocyanate is
generally a secondary or tertiary amine, which may be positively
charged in physiological solutions. Likewise, carboxyl, sulfate,
and phosphate groups, which are generally not reactive with
isocyanates, could introduce negative charge if desired. A
consideration in selecting base polymers, particularly other than
PAOs or others that react only at the ends, is that the process of
adding the reactive groups necessarily requires adding reactive
groups to every alcohol, amine, sulfhydryl, phenol, etc. found on
the base polymer. This can substantially change the properties,
particularly the solubility properties, of the polymer after
activation.
Reactive Groups
[0105] The base or backbone polymer is then activated by capping
with low molecular weight (LMW) reactive groups. In a preferred
embodiment, the polymer is capped with one or more LMW
polyisocyanates (LMW-PIC), which are small molecules, typically
with molecular weight below about 1000 D, more typically below
about 500 D, containing two or more reactive isocyanate groups
attached to each hydroxyl, amine, etc of the base molecule. After
reaction of the LMW-PIC with the backbone, each capable group of
the backbone polymer has been reacted with one of the isocyanate
groups of the LMW-PIC, leaving one or more reactive isocyanates
bonded to the backbone polymer via the PIC. The LMW-PIC are
themselves formed by conjugation of their alcohols, amines, etc.
with suitable precursors to form the isocyanate groups. Starting
molecules may include any of those mentioned above as starting
molecules for forming PAOs, and may also include derivatives of
aromatic groups, such as toluene, benzene, naphthalene, etc. The
preferred LMW-PIC for activating the polymer are di-isocyanates,
and in particular toluene diisocyanate (TDI) and isophorone
diisocyanate, both commercially available, are preferred. When a
diisocyanate is reacted with a capable group on the base polymer,
one of the added isocyanates is used to bind the diisocyanate
molecule to the polymer, leaving the other isocyanate group bound
to the polymer and ready to react. As long as the backbone polymers
have on average more than two capable groups (hydroxyl, amine,
etc.), the resulting composition will be crosslinkable.
[0106] A wide variety of isocyanates are potentially usable in the
invention as LMW-PICs. Suitable isocyanates include 9,10-anthracene
diisocyanate, 1,4-anthracenediisocyanate, benzidine diisocyanate,
4,4'-biphenylene diisocyanate, 4-bromo-1,3-phenylene diisocyanate,
4-chloro-1,3-phenylene diisocyanate, cumene-2,4-diisocyanate,
cyclohexylene-1,2-diisocyanate, cyclohexylene-1,4-diisocyanate,
1,4-cyclohexylene diisocyanate, 1,10-decamethylene diisocyanate,
3,3'dichloro-4,4' biphenylene diisocyanate,
4,4'diisocyanatodibenzyl, 2,4-diisocyanatostilbene,
2,6-diisocyanatobenzfuran, 2,4-dimethyl-1,3-phenylene diisocyanate,
5,6-dimethyl-1,3-phenylene diisocyanate, 4,6-dimethyl-1,3-phenylene
diisocyanate, 3,3'-dimethyl-4,4'diisocyanatodiphenylmethane,
2,6-dimethyl-4,4'-diisocyanatodiphenyl,
3,3'-dimethoxy-4,4'-diisocyanatodiphenyl,
2,4-diisocyantodiphenylether, 4,4'-diisocyantodiphenylether,
3,3'-diphenyl-4,4'-biphenylene diisocyanate, 4,4'-diphenylmethane
diisocyanate, 4-ethoxy-1,3-phenylene diisocyanate, ethylene
diisocyanate, ethylidene diisocyanate, 2,5-fluorenediisocyanate,
1,6-hexamethylene diisocyanate, isophorone diisocyanate, lysine
diisocyanate, 4-methoxy-1,3-phenylene diisocyanate, methylene
dicyclohexyl diisocyanate, m-phenylene diisocyanate,
1,5-naphthalene diisocyanate, 1,8-naphthalene diisocyanate,
polymeric 4,4'-diphenylmethane diisocyanate, p-phenylene
diisocyanate, 4,4',4''-triphenylmethane triisocyanate,
propylene-1,2-diisocyanate; p-tetramethyl xylene diisocyanate,
1,4-tetramethylene diisocyanate, toluene diisocyanate,
2,4,6-toluene triisocyanate, trifunctional trimer (isocyanurate) of
isophorone diisocyanate, trifunctional biuret of hexamethylene
diisocyanate, and trifunctional trimer (isocyanurate) of
hexamethylene diisocyanate.
[0107] In general, aliphatic isocyanates will have longer cure
times than aromatic isocyanates, and selection among the various
available materials will be guided in part by the desired curing
time in vivo. In addition, commercial availability in grades
suitable for medical use will also be considered, as will cost. At
present, toluene diisocyanate (TDI) and isophorone diisocyanate
(IPDI) preferred. The reactive chemical functionality of the
liquids of the invention is preferably isocyanate, but may
alternatively or in addition be isothiocyanate, to which all of the
above considerations will apply.
Methods of Synthesis
[0108] The method will be described in reference to a polymeric
polyol, but it should be noted that the description is also
applicable to a polymeric polyamine, polysulfhydryl, or polyphenol,
or combination of these groups. The term "polymeric polyol" is used
herein to also encompasses polymers containing such groups in
addition to, or in place of, hydroxyl groups, unless otherwise
stated, or unless inherently not possible.
[0109] The objective in the synthesis is to take a backbone polymer
with two or more hydroxyl groups (a polymeric polyol) (or other
derivatizable groups) and convert it into a reactive polymer in
which the reactive groups each carry an active isocyanate group.
The synthesis is preferably accomplished without addition of
solvents, or of catalysts. A preferred method of adding an
isocyanate group to every alcohol is to mix an excess of a
di-isocyanate with the base polymer. For example, mixing ethylene
diisocyanate (an example of a LMW-PIC) with R(OH).sub.n yields
R[OC(.dbd.O)NHCH.sub.2CH.sub.2N.dbd.C.dbd.O].sub.n, which is a
poly-isocyanate polymer with n pendant isocyanate groups. This is
typically accomplished by slow addition of the LMW-PIC to the
polymer at elevated temperatures under nitrogen sparging, to
improve reaction rate and to remove the water generated by the
reaction.
Physical Properties of the Product
[0110] The polymerizable materials of the invention are typically
liquids at or near body temperature (i.e., below about 45 deg. C.),
and preferably are liquid at room temperature, ca. 20-25 deg. C.,
or below. The liquids are optionally carriers of solids. The solids
may be biodegradable or absorbable. The liquid polymerizable
materials are characterized by polymerizing upon contact with
tissue, without requiring addition of other materials, and without
requiring pretreatment of the tissue, other than removing any
liquid present on the surface(s) to be treated. A related property
of the polymerizable materials is that they are stable for at least
1 year when stored at room temperature (ca. 20-25 degrees C.) in
the absence of water vapor. This is because the material has been
designed so that both the reaction that polymerizes the polymers,
and the reactions that optionally allow the polymer to degrade,
both require water to proceed.
[0111] In contrast to previous formulations, the polymeric
polyisocyanates contain a low residual level of low molecular
weight (LMW) polyisocyanates (PIC). For example, the final
concentration of LMW-PIC isocyanate groups in the formulation,
expressed as the equivalent molarity of isocyanate groups attached
to LMW compounds, is normally less than about 1 mM (i.e., 1 mEq),
more preferably less than about 0.5 mEq and most preferably less
than about 0.4 mEq. However, it is preferred that the level of LMW
isocyanate groups be finite and detectable, for example greater
than about 0.05 mEq, and more preferably greater than about 0.1
mEq. It is believed that having a low but finite level of LMW-PIC
molecules tends to promote adherence between the applied polymer
formulation and the tissue being treated. However, decreased levels
of LMW-PIC may tend to decrease tissue irritation during
application and cure of the liquid polymer preparation. It is
believed that the range of about 1 mEq to about 0.05 mEq is
approximately optimal. In situations requiring tissue adherence in
the presence of significant biological fluid, or in adherence to
difficult tissues, greater levels of LMW-PIC isocyanate groups may
be preferred.
Swellability
[0112] The active prepolymers of this invention may form
intertwined polymer chains after reaction that may change their
intertwined geometry under action by fluids within the body. In
particular, one or more components may cause the formed polymeric
material, whether as coating, adhesive, or solid, to swell.
Swelling may have several consequences, and can be controlled. In
one mode, swelling can lead to subsequent break-up (physical
disintegration) of an implant or other final form, rendering the
entire implant absorbable. Or, one or more of the components may
dissolve in the body rendering the remaining components absorbable.
(Dissolvable materials could be added as solids, or as nonreactive
polymers diluting the reactive components.) Or, one or more
components may be biodegradable rendering the remaining components
absorbable. For example, liquids of the present invention
containing a polyethylene/polypropylene random coblock polyol
capped with polyisocyanate are capable of forming elastic gels with
water content as high as 90%. When these polyethylene/polypropylene
polyols are esterified with a carboxylic acid and reacted with a
trifunctional molecule such as trimethylolpropane, or alternatively
when the trifunctional molecule is esterified and reacted with
diols of polyethylene/polypropylene, useful activated polyols are
formed. These polyols, when end capped with a polyisocyanate are
capable of forming gels or solids in a living organism that
decrease in volume and strength over time.
[0113] However, the ratio of propylene oxide to ethylene oxide can
be varied, and the two monomers can be polymerized into block
copolymers, random copolymers, or graft copolymers. These types are
commercially available. While the ethylene oxide groups tend to
absorb water, and so to swell the crosslinked material formed in
the body, the propylene oxide groups are less hydrophilic, and tend
to prevent swelling in aqueous fluids. Thus, the degree of swelling
of the polymerized material in water can be controlled by the
design of the reactive polymers. Another route of swelling control
is by incorporation of non-PAO groups, such as aliphatic or
aromatic esters, into the polymer (as, or in addition to, esters
used to confer degradability.)
[0114] The prepolymer of the present invention is formed by capping
the polyols (as backbone polymer) with polyisocyanate, preferably a
diisocyanate. However, suitable isocyanates have the form
R(NCO).sub.x, where x is 2 to 4 and R is an organic group. Another
approach to creating an in situ polymerizing liquid that
biodegrades in the body is to graft the polyol onto a biodegradable
center. Suitable polymers for inclusion as center molecules are
described in U.S. Pat. No. 4,838,267. They include alkylene
oxalates, dioxepanone, epsilon-caprolactone, glycolide, glycolic
acid, lactide, lactic acid, p-dioxanone, trimethylene carbonate,
trimethylene dimethylene carbonate and combinations of these.
[0115] The center molecule may be a chain, a branched structure, or
a star structure. Suitable star structures are described in U.S.
Pat. No. 5,578,662. Isocyanate capped alkylene oxide can be reacted
with these molecules to form one or more extended chains. The ends
of these chains can therefore participate in crosslinking with
other centers or bond to tissue.
[0116] Center molecules such as those listed above will form rigid
solids upon polymerization. Therefore, it is generally more useful
to ensure at least 80% alkylene oxide is in the final polymerized
structure. Furthermore, the alkylene oxide should be comprised of
at least 70% ethylene oxide.
[0117] These criteria ensure that the polymerized product is
flexible enough to prevent stress localization and associated
tissue bond failure. Furthermore, star molecules in general will
not be preferred since they contain numerous branches. More
numerous branching of the center molecule is associated with higher
liquid viscosity. Furthermore, highly branched prepolymers will
form polymerized products more slowly and with higher modulus. For
example, U.S. Pat. No. 5,578,662 quotes a cross-linking reaction
time of 5 minutes to 72 hours. Both of these characteristics are
undesirable when the prepolymer is intended as a surgical adhesive
or sealant.
Absorbable Compositions and Particulate Additives
[0118] Absorbable prepolymer systems can be composed of
discontinuous (solid) and continuous (liquid) parts. The solid part
may be absorbable or may not be absorbable. One of the simplest
forms of an absorbable implant is one that mechanically breaks into
small pieces without appreciable chemical modification. Fracture of
an implant can be seeded or propagated by the placement of hard
centers in the polymer during formation.
[0119] Mixing the liquid polymer of the present invention with
calcium triphosphate particles will after exposure to fluids or
tissue polymerize into an elastic solid containing an inelastic
particulate. Movement of the surrounding tissue will deform the
elastic implant. Since the particulate cannot deform, stress will
localize around these centers and cracks will begin to propagate
from these centers. In this way, the rate of disintegration and
size of the disintegrated parts can be controlled by varying the
particulate size, the modulus of the formed continuous polymer, and
the density distribution of the particulate.
[0120] Non-absorbable solids are well known and include, as
examples and without limitation, calcium triphosphate, calcium
hydroxylapatite, carbon, silicone, Teflon, polyurethane, acrylic
and mixture of these. Absorbable solids are well known and include,
as examples and without limitation, glycolic acid, glycolide,
lactic acid, lactide, dioxanone, epsilon-caprolactone, trimethylene
carbonate, hydroxybutyrate, hydroxyvalerate, polyanhydrides, and
mixtures of these.
[0121] Other absorbable prepolymer liquids can be composed of two
continuous mechanically mixed parts. For example, one part may be
absorbable and the other not. Consequently, the absorption of one
part results in the mechanical disintegration or weakening of the
implant. Absorbable components may include liquid forms of
cellulose ether, collagen, hyaluronic acid, polyglycolic acid,
glycolide and others well known in the art. These systems are not
excluded in the present invention, but are also not preferred for
the reasons stated above.
Typical Polymer Structures
[0122] There are several ways in which the above-recited steps can
be used to obtain a liquid reactive polymer system useful in the
invention. In a very simple system, a polymeric polyol with a
number of end groups on average greater than two is treated with a
slight excess of a LMW-PIC, such as toluene diisocyanate. The
reaction product is formed under nitrogen with mild heating,
preferably by the addition of the LMW-PIC to the polymer. The
product is then packaged under nitrogen, typically with no
intermediate purification.
[0123] A preferred biodegradable polyol composition includes a
trifunctional hydroxy acid ester (e.g., several lactide groups
successively esterified onto a trifunctional starting material,
such as trimethylolpropane, or glycerol). This is then mixed with a
linear activated polyoxyethylene glycol system, in which the PEG is
first capped with a slight excess of a LMW-PIC, such as toluene
diisocyanate. Then the activated polymer is formed by mixing
together the activated polyoxyethylene glycol and the
lactate-triol. Each lactate triol binds three of the activated PEG
molecules, yielding a prepolymer with three active isocyanates at
the end of the PEG segments, and with the PEG segments bonded
together through degradable lactate groups. In the formed implant,
the lactate ester bonds gradually degrade in the presence of water,
leaving essentially linear PEG chains that are free to dissolve or
degrade. Interestingly, in this system, increasing the percentage
of degradable crosslinker increases rigidity, swell and solvation
resistance in the formed polymer.
[0124] Other polyol systems include hydroxy acid esterified linear
polyether and polyester polyols optionally blended with a low
molecular weight diol. Similarly, polyester and polyether triols
esterified with hydroxy acid are useful. Other polyol systems
include the use of triol forming components such as
trimethylolpropane to form polyols having three arms of linear
polyether chains.
EXAMPLES OF POLYMER SYNTHESIS
[0125] NCO-terminated prepolymers were prepared by mixing each
deionized, dried polyether polyol with each polyisocyanate and
reacting them at 60.degree. C. for 6 hours to 3 days.
Example 1
[0126] A tri-functional polyether polyol was formed by reacting a
PE/PO 80:20 random copolymer having an average MW of 2600 with BASF
Lupamate T80-1 (80:20 2,4- and 2,6-toluenediisocyanate) and
trimethylolpropane (1-5%) to obtain a NCO-terminated hydrophilic
prepolymer having a free NCO content of 3%.
Example 2
[0127] A tri-functional polyether polyol was formed by reacting a
PE/PO 80:20 random copolymer having an average MW of 2600 with IPDI
and trimethylolpropane (1-5%) to obtain a NCO-terminated
hydrophilic prepolymer having a free NCO content of 1.5%.
Example 3
[0128] A tri-functional polyether polyol was formed by reacting a
PE/PO 80:20 random copolymer having an average MW of 2600 (30-20%)
and polyethylene glycol of 1000 MW (30-50%) with IPDI (23-39%) and
trimethylolpropane (1-5%) to obtain a NCO-terminated hydrophilic
prepolymer having a free NCO content of 1.5%.
Example 4
[0129] A tri-functional polyether polyol was formed by reacting a
PE/PO 80:20 random copolymer having an average MW of 2600 (30-20%)
and polyethylene glycol of 1000 MW (30-50%) with BASF Luparnate
T80-1 (80:20 2,4- and 2,6-toluenediisocyanate) (23-39%) and
trimethylolpropane (1-5%) to obtain a NCO-terminated hydrophilic
prepolymer having a free NCO content of 1.5%.
Example 5
[0130] A tri-functional polyether polyol was formed by reacting a
PE/PO 80:20 random copolymer having an average MW of 2600 (5-10%)
and polyethylene glycol of 1000 MW (45-70%) with BASF Luparnate
T80-1 (80:20 2,4- and 2,6-toluenediisocyanate) (23-39%) and
trimethylolpropane (1-5%) to obtain a NCO-terminated hydrophilic
prepolymer having a free NCO content of 1.5%.
Example 6
[0131] A tri-functional polyether polyol Veranol CP 1421 average MW
of 1421 was reacted with BASF Luparnate T80-1 (80:20 2,4- and
2,6-toluenediisocyanate) (23-39%) to obtain a NCO-terminated
hydrophilic prepolymer having a free NCO content of 3.1%.
Example 7
[0132] A tri-functional polyether polyol Veranol CP 1421 average MW
of 1421 was reacted with BASF Luparnate T80-1 (80:20 2,4- and
2,6-toluenediisocyanate) (23-39%) to obtain a NCO-terminated
hydrophilic prepolymer having a free NCO content of 3.1%.
Devices
[0133] A device of the invention can be prepared as is common in
the art from a number of different forms and can consist of a
single instrument with multiple internal parts or a series of
instruments that can be replaceably and sequentially inserted into
a hollow fixed instrument that guides the operational instruments
to a selected location in or adjacent to an annular fissure, or
other site in the spine in need of repair. A detailed description
of an entire apparatus or series of apparatuses for each instance
should not be necessary to enable those skilled in the art to make
a device for, or to practice, the present invention, since most of
the individual components are conventional. The method of the
invention can be accomplished with endoscopic instruments,
automated surgical systems, or any system with structural parts
that function as set forth herein.
[0134] 1. The injector
[0135] A fundamental device of the invention is an injector, which
applies the adhesive polymer or bulking agent to the site. An
example of an injector 610 useful in the invention is shown in a
schematic way (not to scale) in FIG. 2. The device illustrated is
constructed in the same general manner as an intravascular
catheter, although it may be considerably shorter in overall
length. FIG. 2 shows the handle 611, which holds a catheter-like
compound tube 614, which in this embodiment encloses an injection
lumen (not visible) terminating at distal tip 616, and an optical
fiber 617 supplied with visualization device (light source and
viewing screen) 618. The injection lumen connects to a port near to
or within the handle 611 for connecting a polymer source 615, which
as illustrated can be a syringe, but could instead be a pump. The
tube 614, when being introduced into the patient, passes through
the lumen 613 of an introducer 612. The introducer 612 can be as
simple as a hollow needle. An introducer can simply consist of a
hollow needle device or a combination of a simple exterior cannula
that fits around a trocar. The goal is to place a hollow tube
through skin and tissue to provide access into the annulus
fibrosus. More complex variations exist in percutaneous instruments
designed for other parts of the body and can be applied to design
of instruments intended for disc repairs. The distal end 621 of the
introducer will typically be inserted into tissue until it lies at
a location into which material is to be injected. The distal tip
616 of the tube 614 has a viewing port 619 connected to the fiber
optic 617 or equivalent, and a needle tip 628 connected via the
injection lumen to the polymer source 615. A suitable outer
diameter for the tube portion 614 is in the range of 0.2 to 5 mm.
In the illustrated embodiment, the fiber and the injection lumen
are held together inside tube 614, in the manner of an
intravascular catheter. However, the fiber or other visualization
medium could, in an alternative embodiment, be present in a
separate device, for example in a separate needle, in which case
the tube 614 would constitute the injection lumen. In another
alternative, the tube 614 could end at a fixed distance from the
handle, and an injection lumen, carrying the needle tip 628, could
be slidably carried within tube 614, to allow its extension into
the disc without requiring penetration by the viewing system.
[0136] An important optional feature of the injector is the ability
to bend the tube 614 during introduction into the spinal disc. This
is schematically illustrated in FIG. 2 by a dotted outline of the
tube 614 and the distal end 616. A number of methods are known, and
can readily be found in the literature, for making a bendable
injection device. A simple method is to include a wire or other
connector extending from the handle 611 to the tip 616. When the
wire is effectively shortened, for example by pulling or twisting,
then the tube 614 and the tip region 616 are bent to be at an angle
with respect to the handle 611, preferably forming a curve, as
illustrated. Typically, the wire is confined to one side of the
tube 614 (i.e., off-center), to cause bending to occur in a
predictable direction with respect to the handle 611.
Alternatively, wires can be paired, as is known in the control of
catheters. Instead or in addition, all or part of the tube 614 may
be prepared to have an elastic bend, which can be straightened to
allow passage through the introducer 612, but which will re-assume
a bent or curved configuration inside the disc. Other options for
bending the tube can be adapted from the catheter art.
[0137] Visualization, which is preferred but not required, may be
by direct optical imaging, as illustrated above, but may instead or
in addition be by other techniques. Many suitable techniques are
known, including ultrasound, fluoroscopy, and light scattering or
timed optical pulses ("optical tomography"). If a pump is used for
injection, any type of pump can be used that can deliver small
volumes in a predictable way. This can be accomplished, for
example, by small volume piston pumps or syringe pumps; by
pressurization of a reservoir; by peristaltic pumps and similar
devices; and by gravity feed.
[0138] Control of pressure and/or delivery volume can be important.
Control of injection can be provided by placing a pressure
transducer in a suitable location. With pumps, a pressure sensor
can be placed on or in the tube, or at the tip. With a syringe, a
pressure-sensitive pad can be placed on the proximal end of the
plunger, as well as on the tube or in the tip. A pressure sensor
can be coupled to a display, or a gauge, and/or can be coupled to a
microprocessor for automatic or semiautomatic control. In the later
case, the variance of pressure with time can be used to help decide
when injection has been sufficient.
[0139] The injection of the polymer can be used to achieve several
objectives, of which one or all may be used in a particular
procedure. The polymer can be used to form an adhesive. This is
accomplished by depositing a relatively thin layer of polymer on a
surface, or more typically between two surfaces. The surfaces can
be two layers of tissue, or a layer of tissue and a layer of a
prosthetic. The polymer can also be used to form a coating, when
there is space between a surface and another surface. For example,
with care, a coating layer could be deposited on the inner surface
of the annulus after partial or complete removal of a nucleus. The
polymer can also be used to form a bulk deposit. In the context of
treatment of the spine, this will normally be accompanied by
contact of the polymer with surfaces, to which the adhesive polymer
will tend to bond.
[0140] The injector may include one or more additional sensor and
delivery lumens. It may further comprise extraction means for
removing tissue, particularly in the nucleus, to help close a
fissure in the annulus.
[0141] In the procedures described herein, it is advantageous for
the adhesive material to enter into the interstices between the
fibrous structures of the annulus, thereby becoming mechanically
incorporated into the fibrous structure to increase the holding
strength of the adhesive/annulus combination. This may be
particularly important in annulus repair and in securing a disc
nucleus implant within the annulus.
[0142] Other devices are useful in the practice of the invention
and will be described in particular contexts below.
Exemplary Uses
[0143] The following examples of how the polymers and devices can
be used are supplied to clearly illustrate the uses of the
invention.
Herniated Disc Repair
[0144] The paramedial retroperitoneal procedure for exposing the
spine should be used when the herniation, or a substantial portion
of the herniation impinges on the trunk of the spinal nerve. In
this approach entry into the disc is anterior to the defect. When
the herniation is posterior lateral and impinging on one of the
spinal nerve branches, the lateral retroperitoneal approach may be
preferred. The entrance to the disc is preferably opposite the disc
defect.
[0145] When the herniation is anterior of lateral the posterior
lateral approach is preferred. The choices from this approach are
through the lamina or between the lamina and the adjacent vertebral
body. In going between the lamina and the next vertebral body an
expandable trocar of considerable robustness will be required to
increase the opening on this approach. Where the approach is
through the bone of the lamina, the entrance aspect is
substantially perpendicular to the plane of the disc. In such an
approach, some of the techniques described below will not work.
[0146] Treatments for disc herniation of the present invention will
typically include shaping, cutting, or removing portions of the
nuclear material, or all of it. For example, a generalized flow
diagram for augmenting a damaged disc nucleus is given in FIG. 3.
In each case, the annulus is exposed, and a hole is punched into
the annulus. (Each technique will be described below). Three
pathways can be taken from this point. Moving inside the dotted
box, one of a wire, a scraper or a bore is inserted. If a wire,
then, listed on the left, the wire is run along the inner annulus,
completing a loop. The wire is caught, forming a loop; the wire is
pulled through the nucleus, creating a cut in the disk plane. Then
this flat cut is used as the locus for a nucleus augmentation
procedure.
[0147] Another approach to preparing the nucleus for augmentation
is shown in the center. A scraper is inserted into the nuclear
space. The scraper is aligned with the disc plates, and disc
material is scraped from the plates. The scraper is removed, and
suction is applied to remove loose or friable nucleus materials.
Then a nucleus augmentation procedure is begun. On the right,
another approach involves the use of a bore to create tunnels in
the nucleus. The debris is removed if required, and the nucleus is
ready for augmentation.
[0148] These repair techniques are described in more detail in
FIGS. 4 through 7. Referring to FIG. 4, in one preferred
embodiment, a blunt, hollow needle 10 combined with a stylet 12 is
used to dissect the overlying tissue from the skin down to the disc
capsule 14 (FIG. 4b, middle). The needle may, for example, have an
external diameter of 0.050 inch (1.25 mm) and internal diameter of
about 0.038 inch (0.95 mm). The needle 10 has a proximal end fitted
with a luer connection 16 that is connected to a steerable body 18,
such as a syringe (FIG. 4a, top).
[0149] After insertion of the needle 10, with the distal end 20 of
the needle resting on the surface of the disc capsule 14, the
stylet 12 is removed and guidewire 22 is introduced through the
needle lumen (FIG. 4b). Guidewire 22 has tines 24 on its distal end
23 capable of engaging tissue (FIG. 4b inset). Guidewire 22 also
has a graspable member 26 having sufficient diameter or length to
provide sufficient torque to the guidewire 22 to engage tines 24.
With the distal end 23 of guidewire 22 resting on the disc capsule
surface 14, axial pressure is applied along with rotational motion
at the proximal end 26 so as to fixably attach the guidewire 22 to
the capsule surface 14. Once guidewire 22 is engaged then
detachable member 26 is removed and needle 10 is removed.
[0150] Referring to FIG. 4c (bottom), in an alternative embodiment,
dissection through tissue to access the disc capsule 14 is instead
performed using a trocar 28 with blunt, tapered distal end 27. The
trocar 28 is preferably an expandable trocar, having an expandable,
tapered distal end 27 of internal diameter of 0.050 inch (1.25 mm),
for example, and a proximal end 31 having initially a larger
internal diameter, such as 0.25 inch (6.25 mm). The trocar 28 is
fitted with a hollow stylet 32 with internal diameter 0.050 inch
and outer diameter 0.25 inch such that it can be slidably advanced
along guidewire 22. Trocar 28 fitted with stylet 32 is advanced
along guidewire 22 until reaching disc capsule surface 14. During
insertion of trocar 28 tension is applied to guidewire 22
sufficient to control the direction of trocar 28. Stylet 32 is
removed. Trocar 28 may include an expandable sleeve which may be
expanded to retract surrounding tissue and increase access space to
the disc. For example, the expandable sleeve may expanded, using
one or more stylet or obdurator, from the initial 0.05 inch (ca.
1.25 mm), schematically shown at point 30, to as much as 10 to 12
mm (3/8 to 1/2 inch) to provide access to and visualization of the
disc.
[0151] Referring to FIG. 5, an annulus punch, labeled generally as
34, is shown. The annulus punch may be provided in various
diameters. Annulus punch 34 is comprised of engaging member 38
(corkscrew) and cutting hull 40. Engaging member 38 has an outer
diameter matching the inner diameter of cutting hull 40 such that
member 38 is slidable within hull 40. The distal tip 47 of engaging
member 38 may have a fine screw surface 42 as in FIG. 5A, or
engaging and cutting tines 44 as in FIG. 5B, or an open helical
configuration 46 as shown in FIG. 5C. The body of the engaging
member 38 can have a standard screw profile, or a thin profile as
shown in FIG. 5D. Typically the outer diameter of cutting hull 40
will be in the range of 0.1 to 0.25 inch (2.5 to 6.25 mm). If the
outer diameter of punch 34 is less than the inner diameter of
trocar 28, then a stylet 39 is used to match these diameters by
filling the space between them, and guidewire 22 is removed.
Alternatively, no stylet is used and guidance is provided solely by
the guidewire. In this case, punch 34 has a concentric bore 36
running through its center with a diameter matching that of the
outer diameter of guidewire 22 (of FIG. 4c).
[0152] Referring to FIG. 6, one way to use the apparatus of FIG. 5
to remove a core through the annulus is shown. Here, proximal end
48 of engaging member 38 has a slide stop 50, suitable for
grasping, that forces cutting hull 40 with it as engaging member 38
is advanced through tissue. Slide stop 50 is adjusted to the
surface of the proximal end of cutting hull 40 when the distal end
of engaging member 38 is in contact with capsule surface 14. When
engaging member 38 is engaged with capsule surface 14, slide stop
50 is turned so as to advance engaging member 38 through the
annulus 52. During advance, cutting hull 40 cores a cylindrical
volume 54 of annulus 52. Once punch 34 has traversed annulus 52, a
noticeable drop in turning resistance is felt at slide stop 50.
Turning is stopped, and punch 34 is drawn out of trocar 28. This
action removes the cylindrical core 54, detaching from the nuclear
surface 56.
[0153] Referring now to FIGS. 7A-D, in FIG. 7A one embodiment of a
catheter 58 comprising wire member 60 and side-directing distal end
62 is introduced with or without stylet through trocar 28 to
nucleus surface 56. Wire member 60 has blunt end 64 which can pass
through the aperture 66 of side directing end 62. With pressure,
wire member 60 is advanced through aperture 66 and along the inner
annulus surface 68. Wire 60 is sufficiently stiff to cause aperture
66 to force blunt end 64 along inner annular surface 68, while the
blunt end 64 prevents the wire 60 from perforating the surface 68.
Wire 60 is advanced until blunt end 64 returns to the distal end 62
of catheter 58. This can be detected by a combination of distance
of wire pushed, and fluoroscopy. Then, pressure is applied to wire
60 while a pull force is applied to catheter 58 such that catheter
58 is removed leaving wire 60. The result is shown in FIG. 7B.
There is now an opening 98 in wall 56 of the annulus.
[0154] Next, as shown in FIG. 7C, second catheter 72, with or
without stylet, is advanced through trocar 28 until it rests upon
nuclear surface 56. Catheter 72 can be hollow with proximally
actuated engaging loop 74. Alternatively, as shown in FIG. 7D,
catheter 72 has tip 76 with engaging slot 78. In either case,
catheter 72 is engaged with wire end 64. In both cases, both
proximal wire end 80 and loop end 82 or catheter tip 76 is pulled
causing wire 60 to cut a substantially flat plane, labeled 84 in
FIG. 8, through substantially all of the nucleus 86. Radiofrequency
or other energy may be applied to the wire to enhance the cutting
effect.
[0155] 2. Thickening the Disc
[0156] Referring now to FIG. 8, nucleus 86 has plane 84 which can
be accessed through trocar 28. Any number of delivery systems can
be used to deliver tissue adhesive to plane 84. In a preferred
example, a stylet 87 is used that fills the space between an
introducing catheter 88 and trocar 28. (Catheter 88 may be similar
in construction to the injector 610 of FIG. 2, for example.) The
stylet 87 is advanced to nuclear surface 56 and distal tip 90 of
catheter 88 is advanced through the nucleus via plane 84 to the
distal side 92 of the nucleus 86. Dashed lines 88.1 show the
catheter after advancement, and label 90.1 shows the tip location
after advancement. Then adhesive 94, shown exuding from tip 90.1,
is introduced through catheter 88 to bond and thicken nucleus 86.
Adhesive 94 is a liquid and is introduced under pressure, and is
localized by stylet 87, which makes a seal at the capsule surface
14. This arrangement is held in place until tissue adhesive 94
solidifies.
[0157] This procedure, shown without apparatus in FIGS. 9A, 9B and
9C, repairs a herniated or collapsed disc by returning nucleus 86
to a normal thickness via tissue adhesive and bulking agent pumped
into plane cut 84, creating a layer 85 of injected material.
[0158] 3. Pulling Back a Bulge in the Disc
[0159] It may be beneficial to reduce the radius of a herniated
disc, especially when the herniation impinges on vessels or nerves
by adding to the above procedure several additional steps that
either reduce the pressure in the nucleus or actually draw in the
annulus wall.
[0160] Returning now to FIG. 9, after completing the procedure of
FIG. 7 or FIG. 8, an example of additional steps suitable to adjust
the annulus wall includes boring radial channels 96 from annulus
opening 98 to the inner annulus surface 68 using boring techniques
analogous to annulus coring described above. An example of a
suitable nuclear bore 300 is described in FIG. 10. It comprises a
hollow cutting hull 301, shown in 10A, and internal screw-like
grasper 302, the profile of which provides sufficient traction to
distort and actively drive nuclear material onto cutting edge 304.
Cutting edge 304 does not extend beyond blunt profile edge 306, so
that when the bore encounters a substantially solid surface no
further cutting occurs. The inner surface of cutting hull 301 can
be studded with tines 308 whose sides of greatest surface area 309
are aligned with the axis of cutting hull 301. Additionally, the
distal sides 310 of tines 308 are sharp so that when tissue is
drawn into hull 301 the tissue is sliced through with minimal
resistance. Conversely, the proximal sides 307 of tine 308 are
blunt. The tines 308 may be biased proximally at angle 312. As seen
in FIG. 10B, the tines may further be staggered along the axis of
hull 301 such that tines A form a unit in a single plane 314 of
hull 301, from which successive units B and C are arranged on
successive planes 316 and 318, and are created by rotating through
angle 320. The effect is that when the nuclear material is cored
and core 322 and bore 300 are removed, surfaces 309 prevent
rotation of core 322 which prevent it from sliding down screw-like
grasper 302. Further bias 312, blunt edge 307, and grasper surface
324 prevent axial slippage of the core 322 of nuclear tissue.
Alternatively, as shown in FIG. 10C, a biased edge 326 on hull 301
may be substituted for tines 308, or used in addition to them.
Although the bore 300 is one example of a device that can remove
tissue in a controlled way, other devices capable of such removal
can be envisaged.
[0161] Returning to FIG. 9E, a multiplicity of nuclear channels 96
can be made from the same annulus opening 98 by tilting trocar 28
at angle 100 in the disc plane. Pressure can be relieved in the
nucleus 86 by leaving channels 96 hollow and paving over annulus
opening 98 with additional tissue adhesive or suitable mesh coated
with tissue adhesive (FIG. 9D). To retract a bulge, or otherwise
adjust the profile of the disc, a plurality of flexible catheters
102 may be introduced serially into the nuclear channels 96. A
flexible catheter 102 comprises a hollow flexible shaft 104 with
biocompatible strings 106 or wires with tissue snaring end 108
detachably localized on the distal end 110 of catheter 102.
Biocompatible strings or wires 106 may be porous, such as expanded
PTFE or woven stiff threads. First catheter 102 is introduced into
a channel 96 until the distal end 108 touches inner annulus surface
68. Then under axial pressure, catheter 102 is twisted to fixably
engage tissue snare 108 to inner annulus surface 68. First catheter
102 is left in place to help guide a second catheter 102 to a
separate channel 96. When the desirable number of channels are
filled, the hollow flexible shafts 104 of catheters 102 are
removed.
[0162] Next, catheter 109 is introduced into trocar 28 (FIGS. 9F,
9H). Catheter 109 has an inner scalloped or grooved 110 cross
section such that when strings 106 are put under tension they
naturally fall into the groves 110. Second catheter 112 is
introduced into catheter 109. Catheter 112 has a double internal
lumen 114 and 115 and outer radius matching the inner radius 116 of
catheter 109. Catheter 109 and 112 form a sealable surface 116
against capsule surface 14. The proximal end of catheter 112 has a
luer connection 118 (FIG. 9G) connecting to lumen 114 and a port
120 allowing lumen 115 to vent to atmosphere.
[0163] The hernia reduction procedure comprises pulling strings or
wires 106 tight so as to reduce bulging of the annulus 68. Tension
can be applied differentially to strings 106 to affect a
therapeutic annulus shape, as shown schematically in FIG. 9F
compared to FIG. 9E. The proximal end of string 106 can be fixably
attached to the proximal end of trocar 28 to hold strings 106 in
place during the bonding procedure. Second a syringe of tissue
adhesive is loaded on luer connection 118 and adhesive, preferably
if the type described above, and more preferably fast curing, is
advanced down lumen 114 to fill channels 96. Alternatively only the
annulus opening 98 need be filled with adhesive. Once the adhesive
is cured all catheters are removed from trocar 28. The strings or
wires 106 and annulus opening 98 can be planed to smoothness using
a planing auger described later in the section titled Nuclear
Prosthetic Localization, below.
[0164] 4. Removal of Disc Material to Treat Herniation
[0165] The examples described above entail leaving the nucleus
intact to at least some degree. The methods below describe
treatment of disc herniation by removing some or all of the
nucleus. Referring now to FIG. 11, a variation on the wire approach
can be used to completely separate the nucleus from the annulus. As
described above, the nucleus 86 is exposed by coring the annulus. A
channel 130 is made through the nucleus 86, for example with the
bore of FIG. 10. Channel 130 (delineated by dashed lines)
preferably has a cross section of about 10% of the thickness of
disc 132, ranging from about 5% to about 20%. The purpose of
channel 130 is to allow a suitable fluid medium, coming from a
source 160, to flow from first end 134 to second end 136 of channel
130 to fill void 138 as nucleus 86 is removed from annulus 142, for
example by aspiration through a catheter 156, or by removal any
other means, such as a grasper (not shown.). However, channel 130
is not strictly necessary, and should be avoided if the nucleus 86
is friable. Alternatively, a balloon could be placed in space 138
via passage 130 and is inflated, either as the disc nucleus is
removed or by itself to promote disc nucleus removal (not
illustrated.)
[0166] Referring to FIG. 12, an alternative is shown. A bore is
removed, and catheter 143 comprising ribbon member 144 and catheter
145 with side directing end 146 is introduced with or without
stylet through trocar 28 to nucleus surface 56. Wire ribbon member
144 has a blunt end 148 such that it can pass through the aperture
150 of side directing end 152. Additionally, axial edges 154 of
ribbon 144 are sharp (see inset). With pressure, ribbon member 144
is advanced through aperture 150 and along the inner annulus
surface 68. Ribbon 144 is sufficiently stiff to cause aperture 150
to force blunt end 148 along the inner annular surface 68 without
perforating the surface. Ribbon 144 is advanced until blunt end 148
returns to the distal end 146 of catheter 145. Ribbon 144 is then
removed by pulling proximally on the proximal ribbon end (not
shown). Catheter 145 is removed.
[0167] Returning to FIG. 11, subsequently a grasper 156 is placed
on nuclear surface 56 and advanced a sufficient distance into the
nucleus 86. The integrity of nucleus 86 determines how far one must
advance grasper 156. Once nucleus 86 is fixedly attached to grasper
156, grasper 156 is retracted proximally towards 160 to remove the
nucleus 158 in one piece. Grasper 156 could be a catheter 156 for
aspiration, as illustrated, or could be a screw-like grasper, as in
FIG. 10. Alternatively, the ribbon 144 can be inserted first and
then channel 130 created. The first sequence is preferred since
creation of channel 130 allows the nucleus 158 to distort to
accommodate passage of the ribbon 144.
[0168] Alternatively, the grasper 156 can be omitted and the ribbon
144 used to remove the nucleus 158. In this case, when ribbon end
154 appears after traversing inner annulus surface 68, hull 145 is
removed leaving ribbon 144 in place. Then a loop grasper (not
illustrated; analogous to the loop in FIG. 7C) is attached to
ribbon blunt end 148 and grasper 160 and proximal ribbon end 154
are both pulled proximally. For use in this technique, ribbon 144
may have its sharp or serrated edges 154 bent at right angles to
the ribbon plane to effect a cutting action, separating nucleus
from vertebral end plates, as the ribbon is pulled out of the
annulus.
Annulus Repair
[0169] The present invention provides a minimally invasive method
and device for treating discs at selected locations within the
annulus fibrosus. In particular, it relates to fixing the fibers of
the annulus in a preferred orientation and providing increased
rigidity to the annulus by increasing its volume and coupling
adjacent layers of the annulus with a polymerizing fluid.
[0170] One important consequence of delivering tissue adhesive
within the wall of the annulus fibrosus is to increase support and
space between vertebral bodies by inflating tissue that is, by
virtue of its internal structure, constrained laterally such that
the inflating pressure is predominately direct toward the disc
plate surfaces. In the unloaded condition, this force can
substantially improve intervertebral distances without increasing
disc diameter. This improved arrangement is then fixed through
polymerization, both by binding adjacent tissue layers and by
adding bulk to the annulus. In particular, the invention provides a
device that has a distal end that is inserted into the wall of the
annulus and accesses the posterior, posterior lateral and the
posterior medial regions of the annulus fibrosus in order to repair
an annulus at such a location. These and other objects of the
invention have been accomplished by the present invention which
provides methods for manipulating annulus tissue with and without a
fissure or tear in an intervertebral disc, the disc having a
nucleus pulposus and an annulus fibrosus, the annulus having an
inner wall of the annulus fibrosus.
[0171] The method employs an externally guidable intervertebral
disc apparatus, or injector. The injector may be generally similar
to a catheter, for example as described above in FIG. 3, but any
physical arrangement which allows controlled delivery of fluid to a
site, optionally accompanied by visualization of the site or its
surrounding, is suitable. The procedure is performed with an
injector having a distal end, a proximal end, a longitudinal axis,
and an intradiscal section at the injector's distal end on which
there is at least one functional element. The injector is advanced
in the annulus fibrosus in an orientation substantially parallel to
the layers of the annulus by applying a force to the proximal end.
In the case where the annulus is open, the opening may be sealed
with the polymerizing fluid first. The functional element, which
may simply be a hollow needle, is positioned at a selected location
in the disc by advancing or retracting the injector and optionally
twisting the proximal end of the injector. The procedure allows the
administration of tissue adhesive to treat annular fissures.
[0172] A method of treating an annulus comprises the steps of
placing an injector in a plane of the annulus layers and delivering
tissue adhesive in sufficient quantity to strengthen and bond two
or more adjacent layers. This operation may include filling
portions of the nucleus. If the annulus is whole, the fluid may be
injected under pressure sufficient to cause the fluid to separate
and travel between layers encircling the entire disc before
solidifying by polymerization. Once the layers are fully
infiltrated, additional pressure will serve to pressurize the space
between layers, and the natural adhesiveness between the layers of
the annulus directs the inflation pressure substantially in a
directions perpendicular to the plane of the disc plates. This
generated force then serves to increase the intervertebral
distance, preferably to about 10 to 15 mm. This procedure may be
enhanced by several unloading methods known in the art, such as
adjusting patient position, inserting a balloon in the region of
the nucleus and inflating, and various mechanical means for
separating the vertebral plates.
[0173] It may be advantageous to include various measuring means,
for example measuring the fluid pressure inside the delivery device
to control the degree of inflation of the annulus. Various imaging
means, including fluoroscopy and the transmission of light through
the annulus, may be used to directly observe delamination of the
layers of the annulus. Furthermore, the procedure may include the
use of polarized light or fluorescence or similar imaging methods
to directly observe the orientation of the fibers within the
annulus, and accordingly direct delivery efforts.
Annulus Augmentation--Example
[0174] Referring now to FIG. 13, the annulus surface 56 is exposed
at a site where the axis 170 of trocar 28 is collinear with a
tangent 172 at the point 173 of intersection of trocar axis 170 and
a line 174 perpendicular to trocar axis 170 that passes through
disc center 176. It should be appreciated that translation of
trocar 28 laterally in the direction along line 174 satisfies the
above condition but places point 173 at varying depths in the
annulus wall 178. A beveled needle 180, flattened at tip 182 along
a dimension parallel to line 174, is introduced along trocar axis
170 with the flattened dimension of tip 182 perpendicular to the
plane defined by trocar axis 170 and disc bisector 174. Needle 180
is advanced through the annulus wall 178 along tangent 172 until
needle tip 182 reaches intersection 173. This positioning can be
achieved by estimation or fluoroscopy. This action causes needle
180 to cut through some of the layers 184 of the annulus.
[0175] Referring also to FIG. 14, then the wire or ribbon method
previously described is used to delaminate layer 186 from layer 188
of annulus wall 178, thereby forming a pocket 179. Wire or ribbon
190 is left in place. Flexible catheter 192 with proximal end 194
with luer fitting 196 is attached to adhesive syringe 198. Flexible
catheter 192 is carefully primed with adhesive before introduced
into trocar 28. This is done to prevent air injection into the
relatively small volume pocket 179 formed in annulus wall 178.
Flexible catheter 192 has a beveled but blunt end 200. Flexible
catheter 192 may have an external engagement assembly 202 to allow
it to be detachably attached to wire 190. Once catheter 192 is
primed it is attached to wire 190 and introduced into the trocar 28
and advanced to intersection 173.
[0176] At this point catheter 192 may be detached from wire 190 by
rotational motion 204 and wire 190 removed from the annulus wall
178. Alternatively, the wire and attachment may be left in place to
help guide catheter 192. If this alternative is the case, the wire
must be removed before adhesive is administered to pocket 179.
Alternatively, a balloon on the tip of a catheter may be used to
create the delineated space in the annulus wall.
[0177] Catheter 192 is then advanced along pocket 179 until
catheter tip 200 has circumnavigated the annulus wall 178, or
nearly so. Subsequently, pressure is applied to plunger 206 of
adhesive syringe 198 and a small volume of adhesive, e.g. 0.01 cc,
is dispensed forming plug 210. Adhesive syringe 198 should be
small, for example about 1 cc, so that resistance to injection of
adhesive is readily transmitted to the surgeon's hand. The adhesive
is then allowed to cure. Then pressure is applied to plunger 206 of
adhesive syringe 198 while simultaneous pulling proximally on
catheter 192. The rate of catheter extraction should be governed by
the resistance to injection felt by the surgeon at plunger 206. It
should be noted that dispersal of adhesive along the pocket is a
high resistance condition. As catheter 192 is removed resistance to
injection drops. As catheter tip 200 passes through the annulus
pocket 179 dispersing adhesive, resistance to injection of adhesive
will drop noticeably when at locations where pocket 179 intersects
an annulus defect 208. When this drop in resistance is noticed,
retraction of the catheter 192 is halted and adhesive is injected
statically until the defect is filled. Since the portion of pocket
179 is sealed by plug 210 and the body of catheter 192, the pocket
179 can be pressured if desired. The pressure in pocket 179 will
tend to pull aneurysms such as 212 toward disc center 176 due to
hoop stress (arrows, FIG. 14).
Disc Dimensioning
[0178] Sometimes the goal of a nucleus replacement procedure
involves the additional step of increasing the distance between
vertebral plates (increasing disc thickness) beyond what is
achieved by unloading the spinal column. In this case, pressure is
introduced into the nuclear region. This has five clinically
significant effects: 1) it further separates the vertebral plates
and palliates pain associated with nerve damage caused by direct
contact between the plate surfaces, 2) it increases the range of
spinal movement by allowing the planes of the vertebral plates to
be at larger different angles without touching, 3) it provides room
for the normal variations in plate spacing due to acute compressive
forces, 4) it equalizes the spacing in the treated disc with those
of untreated normal discs so as to distribute forces more evenly
along the spinal column, and 5) it reduces stress on the various
branching elements of the spinal chord by restoring proper spacing
between them.
[0179] Additionally, there is a morphological effect associated
with the microscopic structure of the annulus. The annulus is
comprised of concentric layers of tissue. Each layer is comprised
of filaments of collagen arranged in sheets with the orientation of
the filaments within a sheet aligned along one of two principal
directions. The sheets are arranged so that the alignment of fibers
alternate in direction, and the angle formed between fibers
oriented in one sheet and fibers oriented in an adjacent sheet is
substantially greater than zero, and approaches 30-45 degrees in
the preferred case. The structural effect is to alternate layers of
fibers in a crossing pattern such that the tension in an inner
layer of fibers is counter balanced by the tension in an outer
layer of fibers such that the layers maintain their respective
positions within the annulus resulting in restorative forces
counteracting the pressure force in the nucleus which tends to
increase the radius of the annulus. The increase in the radius of
the annulus is responsible for bulging of the disc, which
ultimately leads to disc degeneration and nerve damage.
[0180] The process of annulus degeneration is accelerated when the
radius of the annulus is increased. The effect of reducing disc
thickness along with an increase in disc radius serves to reduce
the angle between fiber layers. As the fibers become substantially
more parallel, i.e., less crossing, the tension in the fibers is
less effective in maintaining the radius of the annulus and
distension occurs. Consequently, the restorative forces necessary
for maintaining proper disc radius and preventing aneurysm or
rupture can be realized in part by restoring (increasing) the
distance between vertebral body plates.
[0181] In the cases where the annulus has ruptured and nucleus
material has extruded outside of its normal confinement within the
annulus, the reduction in fiber angle and resulting increase in
annulus radius is primarily due to a loss of volume within the
annulus rather than a stretching of the fibers. In this case,
especially, repair of the rupture with a surgical adhesive and
subsequently filling of the nuclear space can result in restored
disc thickness and increased tensile strength of the annulus
[0182] While it may be sufficient to fill the nucleus with a fluid
or quasi-fluid material, a preferred material would be introduced
as a fluid and subsequently become solid under unloaded conditions.
Such a material would generate a restorative force in the nucleus
that would tend to return the disc to proper thickness. It is
important to keep in mind that the native nucleus is not a rigid
solid. Therefore, a replacement material should be deformable yet
effectively communicate forces between vertebral plates. Therefore,
it is important that the nuclear replacement bond to the vertebral
plate surfaces and to the wall of the annulus.
[0183] Other unique features of an adhesive in situ polymerizing
fluid used to restore the proper distance between vertebral plates
are its ability to bond to fibers naturally found in the nucleus,
which still maintain structural connection between the vertebral
plates. These fibers can then act as a reinforcing element within
the formed polymerized mass.
[0184] The material of this invention has all of these feature, and
one additional feature of great utility. Since the hydrogel
material formed contains water and is hydrophilic, the occurrence
of calcification in the nuclear space is reduced. The vertebral
plate surfaces are cushioned, but also are effectively protected
against abrasion due to solid calcium deposits in the nuclear
space.
[0185] The method of restoring proper disc thickness with an
adhesive in situ polymerizing material can be used on discs that
are ruptured or merely dilated. The clinical approach in treating
these two distinct conditions may be quite different. For example,
if the annulus is not ruptured any effort to introduce a solid into
the nuclear space will likely results in a severe reduction in
annulus strength. In this case, two things are needed. The nuclear
material which has undergone chemical degradation, including
formation of calcification deposits must be isolated from the
relatively nerve-rich vertebral plate surfaces. Introduction of a
thin injector or needle into the nuclear space must be capable of
maneuvering to a number of locations within the nucleus since even
in the degenerated state the nucleus is not porous enough to allow
fluid introduced at one location to travel to other locations
within the nucleus. In the preferred embodiment the injector forms
a space around the perimeter of the nucleus through which the
polymer solution flows and from which it diffuses into the nuclear
volume. It may also be advantageous to use the same catheter, or
one with greater rigidity, to form intersecting volumes which pass
through the center of the nucleus. The goal is to coat any
degenerated material with hydrogel to chemically and physically
isolate it from nerve endings without removing it.
[0186] Alternatively, if the annulus is already ruptured, the
nuclear material can be removed, and replaced by filling the space
with adhesive. Then the fissure is repaired with the filling
polymer solution or one of greater tensile strength. In both
approaches it is possible to pressurize the nuclear replacement
fluid to attain a final increased disc thickness. This may be
achieved by leaving the injector in place while the polymer
polymerizes, blocking loss of the fluid prior to
solidification.
[0187] Alternatively, the nuclear volume could be filled without
pressure, the injector removed, and a second polymerizing material
used to fill the hole created by the injector. The second fluid
would have a cure time substantially less than the cure time of the
fluid used to fill the nuclear volume. Secondly, the filling fluid
could contain substantially more functional reactive groups, such
as isocyanate in the preferred adhesive, so that normal production
of carbon dioxide during the polymerization is sufficient to create
gaseous carbon dioxide. The repair steps are: 1) the injector is
removed, 2) the hole is bonded closed, and 3) the liquid nuclear
replacement, while curing, produces a volume of carbon dioxide
sufficient to pressurize the nuclear volume before solidification.
The resulting voids created by the carbon dioxide gas are filled
with water from the body as the carbon dioxide dissolves into the
body.
Disc Thickness Augmentation
[0188] In a case where the disc is degenerated to the point where
adjacent vertebral plate surfaces interact pathologically, it may
be sufficient to refill the annulus with an in-situ polymerizing
tissue adhesive. In this instance, the cross section of the
delivery route through the annulus should be minimized to prevent
compromising the integrity of the annulus. The simplest route of
delivery is a small gauge hypodermic needle passed into the nucleus
interior through the annulus. The injection can be performed under
pressure to increase disc thickness and the adhesive should be
allowed to cure before retracting the needle. In the case where a
low cured modulus is beneficial, for example when mimicking the
natural nuclear modulus is an advantage, then injection along a
bias is desired.
[0189] Referring to FIGS. 13 and 15, the annulus is exposed at a
site where the axis 170 of trocar 28 is slightly offset by an angle
220 from a line 222 collinear with a tangent 172 at the point of
intersection 173 formed by a line 174 approximately perpendicular
to trocar axis 170 that passes through disc center 176. Offset
angle 220 is toward disc center 176. Intersection point 173 is on
or near inner annulus surface 224. Axis 170 now defines an
injection path that is long compared to an injection path that
intersects disc center 176. A beveled hollow needle 180, flattened
along a dimension 182 is introduced along trocar axis 170 with
dimension 182 perpendicular to the plane defined by trocar axis 170
and disc bisector 174. Needle 180 is advanced through the annulus
wall 178 until needle tip 182 enters nucleus 226 near intersection
173. This positioning can be achieved by estimation or fluoroscopy.
This action causes needle 180 to cut through layers 184 of the
annulus creating needle track 228.
[0190] Now using the set-up of FIG. 14, beveled hollow needle 180
with proximal end 194 with luer fitting 196 is attached to adhesive
syringe 198. Subsequently, pressure is applied to plunger 206 of
adhesive syringe 198 and a desired volume of adhesive is dispensed.
If the adhesive is dispensed under pressure then when needle 180 is
removed from needle track 228, the needle track will collapse
behind the needle tip 182 as it is removed. Under this condition,
even a very low modulus cured nuclear implant will be blocked from
extrusion out needle track 228.
[0191] Referring to FIG. 16, the above approach may be particularly
beneficial when the nucleus is degraded and comprised of fluids and
loose particulate. In this case, instead of needle 180, flexible
catheter 230 is used with stylet 232. Catheter 230 and stylet 232
form needle track 228, then stylet 232 is removed and catheter 230
is advanced into the nucleus. Blunt tip 234 causes catheter 230 to
follow inner annulus wall 236 coiling around in the nucleus 238.
This action further disaggregates the nucleus. The nuclear volume
238 may be substantially filled with catheter 230. During nuclear
disaggregation suction may be applied to catheter 230 proximally to
aspirate part or all of disaggregated nucleus 238. Then adhesive
may be delivered through catheter 230 to nuclear volume 238 to bond
together disaggregated nuclear parts and fill volume 238. Catheter
230 may be removed in synchrony with filling. Alternatively,
adhesive may be injected into nuclear volume 238, mixed with
disaggregated nuclear parts and subsequently aspirated one or more
times. Each time the aspirated volume is replaced with fresh
adhesive.
[0192] Referring now to FIG. 17, other methods of restoring a disc
400 to its proper thickness 403 include removal of the nucleus 404
and subsequent mechanical expansion of the disc thickness 402. This
can be accomplished with a first adhesive that substantially or
completely polymerizes to make in-situ formed elastic volume 406
which is subsequently filled and pressurized with a second in-situ
polymerizing substance 408. Preferably, the cure time of the first
adhesive is much faster than the cure time of the second
adhesive.
[0193] Using any of the above described techniques, access is made
to the nucleus and all or part of the nucleus is removed. Catheter
410 is introduced into the nuclear space 404 and first adhesive is
injected under light pressure. First adhesive polymerizes filling
nuclear space 404 and sealing catheter 410 to annulus wall 412 with
in-situ formed elastic volume 406. The injection is performed such
that catheter tip 414 is completely surround by volume 406, and
preferably is at the center of 406. After volume 406 is completely
cured, second adhesive 408 is introduced into volume 406. Volume
406 encapsulates second adhesive 408 and expands around it. This
action increases disc thickness 402. Once proper disc thickness 402
is achieved, the volume is allowed to polymerize to allow for
catheter removal. This approach is particularly useful in a
posterior lateral approach where a laminectomy is performed.
[0194] Alternatively, disc thickness 402 can be improved by
"jacking" the disc space using successively applied tapers 416.
Referring to FIG. 18, access 418 is made through annulus 420. A
taper 416 is selected and passed through access 418. Taper 416 has
a cross section wherein primary axis 422 is larger than secondary
axis 424 and secondary axis 424 is aligned with the disc plane 426.
The secondary axis 424 decreases toward distal end 428 of taper 416
while primary axis 422 is unchanged. Multiple tapers may be stacked
such that their primary axes add to increase disc thickness 402.
When the proper disc thickness 402 is achieved, adhesive is
delivered to the nucleus interior 430. After a substantial volume
of the nucleus interior 430 is filled and polymerized, then the
tapers can be removed and the remaining volume filled.
Prosthetic Immobilization
[0195] One embodiment of the present invention provides a method
and apparatus for treating intervertebral disc disorders,
particularly localization and fitting of a nucleus prosthetic,
which may or may not be accompanied with sealing of the access
window in the annulus and subsequent pressurization. The invention
comprises coupling a tissue polymerizing agent with a guidable
intervertebral disc apparatus or injector, as described above, and
using this combination for accessing and delivering an in situ
polymerizing agent at a location in an intervertebral disc having
1) a nucleus prosthetic inserted in the space formerly occupied by
the disc nucleus and 2) at least part of the annulus fibrosus, the
annulus having an inner wall.
[0196] The invention is distinguished from conventional
percutaneous interventions in not being reliant on reference
measurements and selection of appropriate prosthetic sizes. Such
conventional approaches are further complicated by insufficient
range of available prosthetic sizes, typically only one.
Additionally, the present invention can be used with any
insertional apparatus that provides proximity to the disc,
including many such insertional apparatuses known in the art as an
"introducer". An introducer, as described above, has an internal
lumen with a distal opening at a terminus of the introducer to
allow insertion/manipulation of the operational parts into the
interior of a disc.
[0197] The method starts with a standard discectomy, where a window
is formed in the annulus sufficient to accept the nucleus
prosthetic and part or all of the nucleus is removed. Then the
replacement nucleus is inserted into and centered in the cleared
area of the disc. Then the guidable intervertebral injector
apparatus is connected to a source of polymer solution. The tip of
the device is introduced into the nuclear space through the window
and guided through the space between prosthetic and natural disc
annulus to a location approximately 180 degrees from the entrance
point. In this way the dispensed solution fills toward the entrance
point. The solution is injected until just filling the annulus
opening. Then the device is slowly removed, and care is taken to
dispense additional fluid to fill the space evacuated by the
dispensing tip. Once the injector is removed, the location of the
prosthetic can be adjusted and held in place until the polymer
solution become sufficiently viscous to prevent prosthetic
dislocation. The remaining void between the prosthetic and annulus
exterior surface can be filled with additional polymer solution and
allowed to cure. After the prosthetic nucleus is immobilized, the
same polymer solution, or a solution with higher tensile strength
and optionally with reinforcing fillers such as fibers, is injected
to fill the window opening made in the annulus. If there is a
significant fissure in the annulus through which the disk initially
bulged, it can be filled with a high tensile reinforcing solution
first, and then the rest of the space is filled as just
described.
[0198] The prepolymer can be used without addition of an aqueous
solution to prevent polymerization within the delivery device. In
the case where an aqueous solution is mixed with the prepolymer, a
second syringe (or other source) containing polymer solution will
be needed to perform the topping off part of the procedure. If the
prosthetic is sufficiently immobilized, the topping off step can be
accomplished as the device is being removed and before
polymerization.
[0199] In the case where a radio-opaque agent is added to provide
visualization of the procedure during fluoroscopy, it may be
beneficial to orient the fluoroscope such that the position of the
annulus, prosthetic and polymer solution allow one to monitor
movement of the prosthetic during delivery of the solution.
Nuclear Prosthetic Localization
[0200] Referring to FIG. 19, using any of the above described
techniques, access is made to the nucleus and all or part of the
nucleus is removed. Trocar 432 makes a sealed connection 434 with
annulus surface 436. In FIG. 19a (upper left), nucleus prosthetic
438 is introduced down trocar 432 using detachable driver 444 and
passed through annulus opening 440 into nuclear space 442. In FIG.
19b (upper right), the nuclear prosthetic 438 is held by driver 444
at the center of nuclear space 442. Next, (FIG. 19c, lower left),
flexible catheter 446 is introduced around driver 444 and into
nuclear space 442. Adhesive 448 is delivered to nuclear space 442,
such that adhesive flows around prosthetic 438 as described by path
450. Driver 444 is removed and catheter 446 is retracted to a
position outside the disc and within trocar 432. Then a second
application of adhesive is delivered. The result, shown in FIG.
19d, lower right, is that the nuclear space 442, annulus opening
440 and a small portion 452 of trocar 432 are filled with cured
adhesive 448. Subsequently planer 454 is introduced inside of
trocar 432. The outer dimension of planer 454 matched the inner
dimension of trocar 432. Planer 454 has a screw-like cross section
456. The distal end 458 of planer 454 has a flat profile with
slightly raised cutting blades 460 such that when planer 454 is
turned about its axis 462 a smooth planer surface is formed and
trimmings are forced proximally along screw-like surfaces of planer
454. As the planer is advanced distally, the planer first planes
through the layer 452 providing very little resistance. When planer
tip 458 engages annulus opening 440 resistance to turning planer
454 about its axis 462 increases noticeably. After this point a
further full turn is performed to yield a flat surface.
[0201] Alternatively, it is contemplated that a first application
of material, which may or may not be adhesive, is made to partially
fill the disc nucleus space and then the adhesive is applied as
described above to secure the in-situ formed implant in place and
close the opening in the annulus. It is further contemplated that
the implant may be formed in-situ by providing a balloon delivered
inside the disc nucleus and filling the balloon with a suitable
implant forming material. The balloon containing the implant formed
therein may optionally then be secured in place by delivering
adhesive to surround the implant and adhere to the surrounding
annulus.
[0202] As described above, it is believed the ability of the fluid
adhesive to penetrate the interstices of the fibrous annulus wall
will substantially increase the ability to secure a disc nucleus
implant in the proper position and substantially reduce if not
eliminate post-surgical movement or explosion of the disc
implant.
Annulus Defect Repair
[0203] When access to the nuclear space requires a large window be
cut from the annulus, such as in delivery of a nucleus prosthetic,
it may be beneficial to reinforce closure of the annulus opening
with mesh coupled with adhesive. Referring now to FIG. 20, mesh 470
may be positioned outside the annulus opening 472 as in
configuration 474 or inside the annulus opening 472 as in
configuration 476. When configuration 476 is used, pressure within
the nucleus 478 may help seal mesh 470 to annulus opening 472. In
this situation, mesh 470 may have minimal porosity to provide
filling through the mesh without leakage. For example, mesh 470 is
placed behind annulus opening 472. Hypodermic needle 480 pierces
mesh 470 and delivers adhesive 482 behind mesh 470. Adhesive 482
causes mesh 470 to seal against annulus opening 472. When
configuration 474 is used, repair of the nucleus is performed, then
subsequently mesh 470 is laid over the opening and saturated with
adhesive. In this case, mesh 470 is preferably porous.
[0204] It is also contemplated that a balloon may be filled inside
the nucleus to hold the mesh in place as the adhesive holding the
mesh in place cures. The balloon may be removed or may be left in
place, and may be filled with adhesive if left in place inside the
nucleus.
[0205] Referring now to FIG. 21, in some cases the annulus defect
is pre-existing. In this case the treatment may consist only in
repairing the defect without manipulation of the nucleus. The goal
may be to seal the defect and to additionally constrain the outward
bulge 484 of the annulus 486. A surface 488 of the annulus 486 is
exposed. Tissue is dissected away from 486 at sites 490 as much as
possible. Vessels and nerves 492 on the caudal site are gently
retracted away from the annulus surface 488. A dissecting ribbon or
wire 494 is introduced at annulus surface 488. Dissecting ribbon
494 is stiff with preformed radius of curvature 496 which
approximately matches the radius of annulus surface 488. When
ribbon 494 is advanced along annulus surface 488 radius of
curvature 496 forces blunt tip 498 to stay close to annulus surface
488 as it circumnavigates the annulus 486. Ribbon 494 is advanced
until blunt tip 498 emerges on the other side 500 of annulus 486
and is advanced into trocar 502.
[0206] The proximal end 502 of ribbon 494 is attached to mesh 503
end 504 and an additional length of ribbon or wire 506 attached to
mesh end 508. Loop snare 510 is placed into trocar 502 and blunt
tip 498 is engaged. Loop snare 510 is pulled advancing mesh 508 to
annulus surface 488. Flexible catheter 512 is placed into trocar
502 and adhesive 514 is delivered to mesh 503. Catheter 512 is
removed and mesh 503 is advanced around annulus 486 by further
pulling on snare 510 a distance equal to the length of mesh 503.
Mesh ends 504 and 508 exposed and now exposed on opposite sides of
annulus 486. Hollow tube 516 is placed over blunt end 498 of ribbon
494 and wire 506 to form a snare. When hollow tube 516 is
introduced down trocar 502 while placing tension on blunt end 498
and wire 506 tension is placed on mesh 503 and ends 504 and 508 and
brought together. Disc bulge 484 is controllably reduced by this
configuration and held until the adhesive hardens. After the
adhesive hardens, mesh end 504 is trimmed from ribbon 494 and mesh
end 508 is trimmed from wire 506. The free mesh end 504 and 508 are
over lapped and bonded together with an additional application of
adhesive.
[0207] It is possible to repair an annulus defect by coring the
defect and filling the resulting channel with avascular tissue
harvested from the patient at another site. In this case, the
harvested core of tissue is placed in the defect channel and bond
together. Bonding can be accomplished by coating the core with
adhesive before placing in the defect channel or secondarily paving
over the core placed in the defect channel with mesh soaked with
adhesive, or adhesive alone.
Sealing of a Fissure in the Annulus
[0208] In many cases, the proximate cause of a disc repair
operation is the formation of a fissure in the annulus, often
accompanied by protrusion of the nucleus into and/or outside the
annulus. Such fissures in the annulus are most problematic when
they are in the posterior medial segment of the annulus, next to
the spinal cord. Repair of such lesions via the lateral posterior
route has been very difficult with prior art methods.
[0209] In a method of the invention, the fissure defect is repaired
in a simple, minimally invasive manner. Referring to FIG. 22,
first, an introducer as in FIG. 2 is placed in the triangle by
standard methods. To the extent possible, the introducer 612 is
placed so that its tip 621 is positioned just inside the annular
wall, without penetrating deeply into the relatively fluid nucleus.
An injector 610 is inserted through the introducer. A tip 628 for
the tubular portion of the injector is selected that has a
relatively blunt, non-penetrating tip. The injector is rotated so
that the tube 614 tends to curl towards the annulus. This prevents
the tube from simply penetrating into the nucleus as it is
introduced. The tube 614 of the injector is then slowly extended
into the disc, generally following the inner wall of the annulus,
until it reaches the fissure 650. The tip tends to angle into the
fissure 650, since it is not supported by the annulus wall 752.
This deviation can be detected by several methods, including
observation through a fiber, or by fluoroscopy or ultrasound, or by
a decrease in force required for insertion. Then, if not done
previously, the injector is connected with a source 615 of a
self-polymerizing adhesive solution, and the solution is injected
into the fissure 650. Filling is monitored by visualization,
ultrasound, fluoroscopy or other technique. The injector may be
rotated 90 degrees to provide filling in the caudal or sacral
directions. Next, the injector is reoriented if required, and
retracted along the route of entry. Adhesive may be injected during
withdrawal to fill the space created by entry, if required. The
adhesive bonds to the walls of the fissure and cures in situ,
bonding the surfaces of the fissure together via a resilient body
of self-crosslinked adhesive.
[0210] For such an application, a relatively short cure time is
preferable, to prevent migration of adhesive towards the spinal
cord. The degree of hydration of the adhesive should be minimal, to
attain maximum cured modulus and prevent bulging of the repair
site. The use of additives fibers and other reinforcing materials
providing resistance to tearing is potentially beneficial.
Encapsulated Nucleus Replacement
[0211] An encapsulating skin is useful to isolate tissue from an
uncured polymer solution, especially if the cure time is long. An
encapsulating skin can act as a restraining force, increasing the
effective modulus of the formed implant. Such a skin can further
generate an internal pressure in the hydrogel if the skin is formed
before appreciable carbon dioxide is released due to polymerization
of the bulk volume of the polymer solution. Alternatively, the skin
can generate increased pressure when addition amounts of polymer
solution or aqueous solution are added.
[0212] Such a skin can reinforce a failing annulus, prevent leakage
prior to polymerization during injection into the nucleus, and be
used to generate an internal pressure sufficient to increase the
intervertebral distance. When the modulus of the skin is more than
the modulus of the internally polymerized hydrogel, then the skin
hydrogel system can be tailored to approximate the functional
structure of the nucleus/annulus system, or disc.
[0213] Such a skin can be made by using the adhesive materials of
the invention to pre-treat tissue or to pre-coat a surface of a
void, for example from removal of a nucleus, intended to be filled
later with the polymer solution. The adhesives act to form a skin
on the tissue solution before the bulk volume of the polymer
solution is inserted, or before it begins to gel. This skin is
fully encapsulating and acts as a restraining force. Depending on
the type of agent used, this skin can be made hard or elastic.
[0214] To achieve the skin effect, it is helpful if the polymer on
the tissue surface can polymerize faster than the bulk polymer.
There are various catalysts and crosslinking agents that can be
used to accelerate the polymerization reaction. The catalysts
include salts of tin. The crosslinking agents include free
isocyanates, difunctional amines and various amino groups, e.g.,
lysine. Such materials, and/or other accelerants of polymerization,
can be applied to tissue before applying the bulk polymeric
solution. Methods of application of the faster curing fraction
include spraying or painting directly to tissue, before or
concurrently with application of the polymerizable adhesive
material.
Nucleus Replacement
[0215] The present invention may be useful in polymerizing and
enhancing the integrity of tissue-derived gels, for example derived
fro components of the nucleus, which may be present in the
intervertebral space. Such gels, when infused with the adhesive of
the present invention, become substantially more rigid and do not
flow. This feature is also important in binding chemicals produced
in a diseased disc, to prevent them from migrating to nerves and
stimulating pain. The polymerization is not limited to the gel
bulk, but may serve to elastically fix and structurally enhance the
attachment of the endogenous gel to tissue and bone.
[0216] The polymerization and adjacent bonding does not require the
polymerizing material to be delivered directly to the target site.
When the solubility of the polymer is high and the cure time is
long the adhesive prepolymer will diffuse throughout the nuclear
space and become well mixed with the endogenous tissue before
fixation.
[0217] Additionally, the material of the present invention may be
mixed with any of the following to create a tissue bonding solid
mass in situ: bone, metallic particulate, hydroxylapatite, carbon
spheres, precipitating polymer solutions such as EVOH and DMSO.
[0218] Moreover, the material of the present invention may be
placed in the nucleus of the disc under pressure to increase, or
return to an appropriate distance, the spacing between vertebral
bodies. The liquid polymer solution under pressure is capable of
solidifying while the injector is in place. The injector can then
easily be removed once the polymer is solid, thus providing a
self-sealing nucleus replacement and/or augmentation therapy
without compromising the integrity of the annulus. These nucleus
augmentation methods can also be performed after a discectomy. The
polymer hydrogel formed within the nucleus substitutes for the
natural nucleus.
[0219] Generally, nucleus replacement devices need to be localized
within the nucleus of the disc to prevent impinging on the spinal
cord or associated branched nerves. The degree of localization
determines the modulus requirements of the implant. For example,
when a large window is made in the annulus for introducing a
nucleus replacement device, the replacement device must have a high
modulus, typically greater than 6000 psi, to prevent extrusion of
the device through the large opening in the annulus. These high
modulus devices essentially replace the functionality of the entire
disc. If in other cases, the opening in the annulus is small
compared to the nuclear space or can be closed after insertion of
the replacement device, the annulus plays a role in supporting the
disk thickness. Essentially, forces applied along the axis of the
spine which tend to compress the nucleus are translated to the wall
of the annulus in much the same way pressure applied to the gas in
a tire is supported by the tire wall. As in the instance of the
tire, the filling medium can have a low modulus. The basic
requirement of a successful nucleus replacement device is that its
modulus be large enough that the pressure required to extrude the
implant through the opening in the annulus is greater than the
pressure required to dilate the opening in the annulus. This
assumes, of course, that the nucleus replacement device is
substantially larger than the opening in the annulus.
[0220] Thus, there are three conditions that may be present in
nucleus replacement: 1) the nuclear replacement device is smaller
than the opening in the annulus and thus must be localized by a
tissue bond or a post-implant dilation of the device and must
possess a very high modulus, typically greater than 1000 psi; 2)
the nuclear replacement device is larger than the opening in the
annulus and the modulus of the device is moderate such that the
pressure required to extrude the device through the opening exceeds
the pressure to dilate the opening, and 3) the opening in the
annulus is either closed or very small and the modulus of the
device can be arbitrarily small.
[0221] Consequently, a replacement device can span a broad range of
moduli. Factors that reduce modulus and enhance flexibility of the
spine include: 1) bonding the implant to the vertebral plates, 2)
maximizing the implant volume relative to the opening in the
annulus, and 3) minimizing and/or post-operatively repairing the
opening in the annulus. It is clear that a liquid tissue adhesive
that forms a solid flexible implant is an ideal nucleus replacement
device, or an important adjunct to the use of a pre-formed nucleus
replacement device.
[0222] In some cases a large defect in the annulus is already
present. In this case there are high modulus pillow-like implants
available on the market that are substantially disc replacement
devices. These high modulus devices must be smaller than the
annulus opening to be successfully implanted. Some expand after
implantation, but do not expand rapidly enough to prevent movement
of the implant within the nuclear space causing pain. Consequently,
there is a need for a space filling liquid polymer that can act to
fill a void within the implant/nucleus combination that bonds the
implant within the disc. Additionally, it is advantageous to have
the polymer liquid bond to the implant to prevent extrusion of the
space-filling polymer. These objectives can be met by injecting a
suitable amount of the adhesive polymer solution of the invention,
and if required maintaining the position of the prosthetic until
the adhesive has cured. It is also possible to use a balloon, for
example carried on a catheter or similar device, to shape or expand
the nuclear space. A deflated balloon is positioned inside the
annulus, and then it is inflated
Other Features
[0223] The present invention is intended to replace or augment
traditional functional elements including: energy delivery to
shrink or modify tissue, means for delivering material, use of
sealants to seal tissue, insertion of solid replacement parts. The
present invention may be incorporated with or delivered in addition
to electrolytic solutions (such as saline), contrast media (such as
Conray meglumine iothalamate, or tantalum powder), pharmaceutical
agents, disinfectants, filling or binding material, or
chemonucleolytic agents.
[0224] A variety of materials can be delivered to the fissure,
including but not limited to electrolyte solutions, contrast media,
pharmaceutical agents (such as the steroid methylprednisolone
sodium succinate available from Pharmacia & Upjohn, Kalamazoo,
Mich., nonsteroidal anti-inflammatory drugs and/or pair
medications), chemonucleolytic enzyme (e.g. chymopapain),
alternative or biological hydrogels (such as disclosed in U.S. Pat.
No. 4,478,822), osteoinductive substances (e.g. BMP, see U.S. Pat.
No. 5,364,839), chrondrocyte inductive substance (e.g. TGG-beta).
The materials may be administered sequentially or simultaneously,
such as beginning with an electrolyte (which aids in viewing), then
following with products to effect a desired healing outcome. These
materials are to be mixed with the polymer solution such that when
it solidified or polymerizes, the materials are incorporated into
the resulting hydrogel matrix and are available to act
therapeutically.
[0225] In particular, the present invention may be useful in
polymerizing and enhancing the integrity of gels present in the
intervertebral space. Such gels, infused with the adhesive of the
present invention, become substantially more rigid and do not flow.
This feature is important in binding chemicals produced in a
diseased disc to prevent them from migrating to nerves an affecting
pain. The polymerization is not limited to the gel bulk, but serves
to elastically fix and structurally enhance the endogenous gel to
tissue and bone. The polymerization and adjacent bonding does not
require the polymerizing material to be delivered directly to the
target site. When the solubility of the polymer is high and the
cure time is long the gel will become well mixed with the
polymerizing material before fixation.
[0226] The method of the present invention may include the use of a
mesh or absorbent biocompatible material to be inserted in a
compressed or rolled state in the access hole and released into a
cavity or space made in the nucleus pulposus. The cavity will be of
sufficient size to allow the mesh to be opened, and will have at
least one wall of the cavity located at the transition between
annulus and nucleus such that the mesh can be placed planar to this
transition. Subsequently, an injector is introduced through or
around the mesh, so that polymer solution can be delivered through
or behind the mesh and is allowed to cure. When the cavity is later
filled and cured, the resulting fluid pressure is confined by the
mesh. Subsequently, the cured polymer both seals the absorbent mesh
and bonds it into place such that the implant volume is
constrained.
[0227] The material of the present invention may be mixed with
fibers, for example flock, to increase its tear resistance after
polymerization without increasing prohibitively, the injectability
of the solution. Additionally, selecting solutions with a higher
proportion of polymerizing agent to aqueous solution creates a more
rigid gel. Typically, the gel modulus can be controlled from a very
loose gel to one of 50D Shore or greater. The material of the
present invention may be used in conjunction with other disc
therapies, including but not limited to disc replacement implants,
cages and bone cements.
[0228] Additionally, the material of the present invention may be
mixed with any of a number of materials to create a tissue bonding
solid mass in-situ, including without limitation bone and bone
particles, metallic particulate, hydroxylapatite, carbon spheres,
and precipitating polymer solutions such as EVOH in DMSO.
[0229] While each of the components of the invention could be
provided separately, it will generally be preferred to combine the
elements of the invention into a kit for performing a particular
spinal operation. The kit will contain the correct amount of
surgical adhesive for the procedure. In addition, the kit will
contain, in sterile form, the particular devices needed for the
procedure. These will be selected from introducers, catheters,
corers, wires, meshes, etc, as required for the particular
procedure. Typically there will at least be an introducer or
trocar, and a delivery device for the adhesive such as a syringe or
catheter. In addition, the kit will typically contain or be
provided in association with a set of directions for using the
components to perform the procedure. As can be seen from examples
above, the procedure can be quite complex; even with training, a
detailed set of directions is desirable and potentially
important.
[0230] While examples have been provided to illustrate the
invention, its scope is not to be limited by the description or its
examples, but only by the appended claims.
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