U.S. patent application number 16/785522 was filed with the patent office on 2020-08-13 for demineralized bone fiber implant compositions and methods for augmenting fixation in bone repair.
The applicant listed for this patent is Theracell, Inc.. Invention is credited to Gunnar Andersson, Andrew J. Carter, Ian McRury, Bradley E. Patt, Nelson L. Scarborough, Nikhil Verma.
Application Number | 20200254143 16/785522 |
Document ID | 20200254143 / US20200254143 |
Family ID | 1000004810195 |
Filed Date | 2020-08-13 |
Patent Application | download [pdf] |
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United States Patent
Application |
20200254143 |
Kind Code |
A1 |
Carter; Andrew J. ; et
al. |
August 13, 2020 |
DEMINERALIZED BONE FIBER IMPLANT COMPOSITIONS AND METHODS FOR
AUGMENTING FIXATION IN BONE REPAIR
Abstract
A composition and methods of making or use thereof include a
plurality of fibers forming a shape for augmenting fixation of a
bone screw, or the plurality of fibers form a shape having a peg
portion and a sheet portion to augment tendon to bone repair. The
physical presence of the plurality of fibers provides initial
fixation, while the use of an osteoinductive material provides long
term enhancement of bone formation around the site of the bone
screw or the tendon to bone repair.
Inventors: |
Carter; Andrew J.; (Stow,
MA) ; Patt; Bradley E.; (Sherman Oaks, CA) ;
Andersson; Gunnar; (Sherman Oaks, CA) ; McRury;
Ian; (Sherman Oaks, CA) ; Verma; Nikhil;
(Sherman Oaks, CA) ; Scarborough; Nelson L.;
(Sherman Oaks, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Theracell, Inc. |
Sherman Oaks |
CA |
US |
|
|
Family ID: |
1000004810195 |
Appl. No.: |
16/785522 |
Filed: |
February 7, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62803470 |
Feb 9, 2019 |
|
|
|
62901935 |
Sep 18, 2019 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 2/30965 20130101;
A61B 17/86 20130101; A61F 2002/30205 20130101; A61L 27/3608
20130101; A61L 27/3695 20130101; A61B 17/686 20130101; A61F
2002/30235 20130101; A61B 17/16 20130101; A61L 27/365 20130101;
A61B 17/8897 20130101; A61F 2002/30224 20130101 |
International
Class: |
A61L 27/36 20060101
A61L027/36; A61F 2/30 20060101 A61F002/30; A61B 17/86 20060101
A61B017/86; A61B 17/88 20060101 A61B017/88 |
Claims
1. A composition, comprising an implant for bone repair, the
implant comprising: a plurality of fibers selected from
demineralized bone fibers (DBF), biocompatible polymer fibers,
collagen fibers, and/or resorbable polymer fibers; wherein the
plurality of fibers form a shape of a cylinder, a tube, a
cannulated cylinder, a truncated cone, a cannulated truncated cone,
a truncated cone with a flared end, or a cannulated truncated cone
with a flared end, tube with a flared end, or a truncated cone
shape, wherein the implant has a proximal end and a distal end, and
wherein the flared end is at the proximal end of the implant.
2. The composition of claim 1, wherein the plurality of fibers
comprise demineralized bone fibers (DBF).
3. The composition of claim 1, wherein the implant has a volume of
between 0.15 cm.sup.3 to 10 cm.sup.3.
4. The composition of claim 1, wherein the implant has a length of
between 1 cm to 10 cm.
5. The composition of claim 1, wherein the flared end comprises an
indent for receiving a bone screw.
6. The composition of claim 1, wherein the implant is
dehydrated.
7. A method of augmenting fixation of a screw in a bone with the
implant of claim 1, the method comprising: optionally placing a
guide wire to define a position in the bone for the screw;
inserting or providing the implant to a cavity in the bone; and
inserting or providing the screw into the implant.
8. The method of claim 7, wherein when the guide wire is used, the
providing the implant comprises placing the implant on the guide
wire through the cannulated, tubular, or cone shape of the implant
and moving the implant along the guide wire into the cavity.
9. The method of claim 7, wherein the moving the implant along the
guide wire comprises using an awl, a pusher, a tap, and/or a
drill.
10. The method of claim 7, wherein the cavity in the bone is formed
using an awl, a pusher, a tap, and/or a drill.
11. A method of augmenting fixation of a screw in a bone with the
implant of claim 1, the method comprising: placing a guide wire to
define a position in the bone for the screw; inserting or providing
the implant to a cavity in the bone; and inserting or providing the
screw into the implant.
12. The method of claim 11, wherein the inserting or providing the
implant or the screw comprises using a cannulated instrument.
13. The method of claim 11 wherein the inserting or providing the
implant comprises an open-ended syringe comprising the implant.
14. A method of fabricating the implant of claim 1, the method
comprising: dispersing the plurality of fibers in a fluid; wherein
the plurality of fibers and the fluid are in a ratio of between
about 1 gram of fibers to about 3 mls to 50 mls of the fluid; and
providing the dispersed plurality of fibers with pressure into a
vented mold thereby draining the fluid from the mold.
15. The method of claim 14, further comprising heating the
plurality of fibers in the mold at or between about 35 to 55
degrees Celsius.
16. The method of claim 14, wherein the plurality of fibers
comprise demineralized bone fibers, biocompatible polymer fibers,
collagen fibers, and/or resorbable polymer fibers.
17. The method of claim 14, wherein the plurality of fibers are
lyophilized.
18. A kit for augmenting fixation of a screw in a bone with an
implant, the kit comprising: the implant of claim 1.
19. The kit of claim 18, further comprising: a guide wire; an awl
or a tap; and/or a screw to be place in the bone to be
repaired.
20. The kit of claim 19, wherein the guide wire and the awl or the
tap are disposable.
Description
[0001] This application claims priority to co-pending U.S.
Provisional Application No. 62/803,470 filed on Feb. 9, 2019 and
U.S. Provisional Application No. 62/901,935 filed on Sep. 18, 2019
the entire contents of all of which are herein incorporated by
reference.
FIELD OF THE INVENTION
[0002] The field of the invention relates to composition and
methods of bone fiber implants made from cortical bone in which a
plurality of demineralized bone fibers forms a shape having a peg
portion and a sheet portion to augment tendon to bone repair.
BACKGROUND
[0003] The background description includes information that may be
useful in understanding the present disclosure. It is not an
admission that any of the information provided herein is prior art
or relevant to the presently claimed invention, or that any
publication specifically or implicitly referenced is prior art.
[0004] All publications and patent applications herein are
incorporated by reference to the same extent as if each individual
publication or patent application were specifically and
individually indicated to be incorporated by reference. Where a
definition or use of a term in an incorporated reference is
inconsistent or contrary to the definition of that term provided
herein, the definition of that term provided herein applies and the
definition of that term in the reference does not apply.
[0005] Worldwide, osteoporosis causes more than 8.9 million
fractures annually, resulting in an osteoporotic fracture every 3
seconds. Osteoporosis is estimated to affect 200 million women
worldwide--approximately one-tenth of women aged 60, one-fifth of
women aged 70, two-fifths of women aged 80, and two-thirds of women
aged 90. Osteoporosis affects an estimated 75 million people in
Europe, USA and Japan. For the year 2000, there were an estimated 9
million new osteoporotic fractures, of which 1.6 million were at
the hip, 1.7 million were at the forearm and 1.4 million were
clinical vertebral fractures. Europe and the Americas accounted for
51% of all these fractures, while most of the remainder occurred in
the Western Pacific region and Southeast Asia. Worldwide, 1 in 3
women over age 50 will experience osteoporotic fractures, as will 1
in 5 men over age 50.
[0006] Modern spine surgical techniques encounter difficulty in
achieving and maintaining fixation in osteoporotic vertebrae in the
case of fracture and/or deformity. The bone-screw interface is
typically the region most susceptible to loosening and failure.
Many physical factors may affect the final fixation strength of
pedicle screws such as screw pitch and diameter, yet host factors
have at least as much effect. Pedicle screws have been shown to
loosen in patients with compromised bone strength arising from
renal osteodystrophy and osteoporosis. A significant portion of
these cases will sustain catastrophic failure after attempted
surgical fixation. As a result, some spine surgeons may refuse to
perform stabilization surgery on osteoporotic patients with
fractures and/or severe deformities. There have been many attempts
to improve the holding capacity of pedicle screw constructs in
osteoporotic bone including the addition of various cements for
augmentation and the use of novel screw designs such as expandable
screws. Use of polymethylmethacrylate (PMMA) cement has been shown
to increase pull-out strength up to 150%. Use of cement to augment
traditional pedicle screw fixation generally yields increased
resistance to pullout and/or toggle failure in the cephalad-caudad
direction as reported in numerous studies, but there are associated
potential morbidities such as spinal canal extrusion or vascular
flow obstruction.
[0007] A further and significant disadvantage of the use of PMMA
screw augmentation is that it is a non-biological repair that make
revision or re-operation very difficult. It is a "bridge burning"
procedure.
[0008] Similar problems of initial fixation strength and subsequent
loosening and failure exist with the use of screws in orthopedic
procedures such as hip fractures that often occur in patients with
osteoporotic or otherwise compromised bone.
[0009] Moreover, there is a desire for implants to bond effectively
and rapidly to surrounding bone, particularly when that bone is
compromised. Various strategies are employed to facilitate this
including the use of porous ingrowth surfaces. Implant loosening
however remains a problem and concern to orthopedists.
[0010] When tendon or ligament tissues or grafts are placed either
in apposition to bone, as in the case of rotator cuff repair or in
bone tunnels as in anterior cruciate ligament repair, the creation
or recreation of the tendon-bone enthesis is a problem and concern
to orthopedists.
SUMMARY OF INVENTION
[0011] The inventors have advantageously discovered a composition
and method of improving the fixation of implants and tissue to bone
through the use of an implant, which may, for example, be composed
of a plurality of fibers of demineralized bone (i.e., demineralized
bone fibers (DBF), collagen fibers, synthetic polymers, resorbable
fibers) and formed into an appropriate shape. The implant according
to some embodiments of the present invention may be placed at i)
the interface between the tissue and bone, or ii) may be placed in
a hole of a bone prior to insertion of a screw.
[0012] In some embodiments of the present invention, a composition
and method are provided for improving the fixation of screws in
bone using a fiber implant as disclosed herein. For example, the
fiber implant may be composed of a plurality of fibers that are
formed into an appropriate shape. Using the implant, kits, and/or
methods as disclosed herein, the implant is placed in the hole in
the bone to be repaired. More specifically, the implant is placed
in the hole of the bone in which a bone screw it to be placed. By
placing the implant in the hole of the bone prior to the insertion
of the screw, the implant contacts the implant and provides a
denser substance into which the screw may be secured, thereby
increasing the insertion torque and the force required to pull the
screw back out of the hole. As such, the implant provided in the
hole of a bone prior to insertion of a bone screw decreases the
chances of the screw being able to dislodge from the hole and
allows for a more secure and effective bone repair. For example, as
demineralized bone fibers (DBF) are both osteoinductive and
osteoconductive, there is an additional benefit of an DBF fiber
implant providing an increase in the local bone growth around the
implant and further increasing the likelihood of a long term and
possibly permanent bone repair. Additionally, other fiber forms
(e.g., collagen fibers, biocompatible polymer fibers, and/or
resorbable polymer fibers) may also be osteoinductive and/or
osteoconductive. The benefits of these fiber implants are of
particular relevance when the screw is being implanted into
osteoporotic bone or into an existing screw hole, as in the case of
revision surgery.
[0013] Notably, the inventive subject matter includes an implant
for bone repair or screw fixation, wherein the implant includes a
plurality of fibers forming a shape of a cylinder, a tube, a
cannulated cylinder, a truncated cone, a cannulated truncated cone,
a truncated cone with a flared end, or a cannulated truncated cone
with a flared end, tube with a flared end, or a truncated cone
shape. In preferred embodiments, the plurality of fibers are cut
from demineralized cortical bone. Further, the implant has a
proximal end and a distal end. For screw fixation, preferably, the
plurality of fibers form the shape of a truncated cone with a
flared end, a tube with a flared end, or a cannulated truncated
cone with a flared end, and the flared end is at the proximal end
of the implant. The length of the implant may be of between 1 cm
and 10 cm. Preferably, the length of the implant is 4 to 5 cm. More
preferably, the implant has a length of 4 cm. The volume of the
implant having a length of between 1 and 10 cm, may also have a
volume of between 0.15 cm.sup.3 to 10.0 cm.sup.3. More preferably,
the volume of the implant may be of between 0.15 cm.sup.3 to 2
cm.sup.3.
[0014] Typically, the flared end of the implant has an indent for
receiving a bone screw.
[0015] In other typical embodiments, the implant is dehydrated.
[0016] The inventive subject matter also includes methods of
augmenting fixation of a screw in a bone with the implant disclosed
above and herein, in which optionally a guide wire may be placed to
define a position in the bone for the screw, followed by inserting
or providing the implant to a cavity in the bone, and then
inserting or providing the screw into the implant.
[0017] Specifically, when the guide wire is used, the method
includes placing the implant on the guide wire through the
cannulated, tubular, or cone shape of the implant and moving the
implant along the guide wire into the cavity, facilitating
placement of the implant and also preventing or decreasing the
incidence of the implant buckling. For moving the implant along the
guide wire, a custom pusher, an awl, a tap, and/or a drill may be
used. Additionally, the cavity in the bone may be formed using an
awl, a tap, and/or a drill. The formation of the cavity using the
awl or tap reduces the incidence of any removal of the bone and
inducing compaction to reinforce fixation of the screw in the bone.
The cavity in the bone may be provided with additional
demineralized bone fibers (DBF), biocompatible polymer fibers,
collagen fibers, and/or resorbable polymer fibers.
[0018] In preferred embodiments, the method of augmenting fixation
of a screw in a bone with one of the presently disclosed implants
includes placing a guide wire to define a position in the bone for
the screw, thereby decreasing the incidence of buckling of the
implant, inserting or providing the implant to a cavity in the
bone, and inserting or providing the screw into the implant wherein
the inserting or providing of the implant or the screw includes
using a cannulated instrument or an open-ended syringe with the
implant contained therein. The implant may be made of demineralized
bone fibers (DBF), biocompatible polymer fibers, collagen fibers,
and/or resorbable polymer fibers, and the implant may be provided
with additional fibers of the same or different type as disclosed
herein. The implant made of the DBF fibers may be both
osteoinductive and osteoconductive.
[0019] The inventive subject matter also includes methods of
fabricating the fiber implant. A method of fabricating the
presently disclosed fiber implant includes dispersing a plurality
of fibers (DBF, biocompatible polymer fibers, collagen fibers,
and/or resorbable polymer fibers) in a fluid, wherein the fibers
and the fluid are in a ratio of between about 1 gram of fibers to
about 3 mls to about 50 mls of the fluid, providing the dispersed
plurality of fibers with pressure into a vented mold thereby
draining the fluid out of the mold. Preferably, the fibers and the
fluid are in a ratio of 1 gram of fibers in about 3 mls to 20 mls
of fluid. More preferably, the fibers and the fluid are in a ratio
of 1 gram of fibers in about 3 mls to 10 mls of fluid.
[0020] In additional embodiments, the method disclosed above and
herein also includes heating the plurality of fibers in the mold.
Preferably, the heating occurs at or between about 35 to 55 degrees
Celsius. In some embodiments, the method also includes lyophilizing
the plurality of fibers.
[0021] The inventors have also contemplated a kit for augmenting
fixation of a screw in a bone, wherein the kit includes at least
one of the presently disclosed fiber implants as disclosed above
and herein. The contemplated kit may also include a guide wire, an
awl or a tap, and/or a screw to be place in the bone to be
repaired. In some embodiments, the guide wire, the awl, and/or the
tap are disposable.
[0022] In addition to screw fixation, the inventors of the
presently disclosed subject matter have discovered an advantageous
implant for the surgical reattachment of tendon to bone. The
presently disclosed implant is at once capable of: 1) providing an
osteoinductive and osteoconductive implant to facilitate
regeneration of the enthesis, 2) augmenting the effectiveness of
the suture anchor, and 3) self-stabilizing during surgery unlike
other implants. Accordingly, aspects of embodiments of the present
invention are directed to a means of improving the fixation of
implants and tissue to bone through the use of an implant, which
may, for example, be composed of fibers of demineralized bone,
collagen, polymer, and/or resorbable polymer fibers, and formed
into an appropriate shape. In particular, the implant made of a
plurality of fibers has a peg portion and a sheet portion.
According to some embodiments of the present invention a suture
anchor may be placed into the peg portion of the implant and the
suture anchor driver is then used to hold the implant and suture
anchor to allow the combination to be introduced into the joint
being treated. By placing the peg portion of the implant into the
cavity placed to receive the suture anchor and screwing the suture
anchor into place, the sheet portion of the implant is held in the
desired place on the bone bed where the tendon is being reattached.
In this way, the sutures can be used to reapproximate and tie down
the tendon to effect repair. For larger repairs multiple implants
may be used.
[0023] In some embodiments of the present invention, the implant is
placed at the interface between a torn rotator cuff tissue and the
bone. The implant according to some embodiments of the present
invention serves to improve the integration between the tendon and
bone and facilitate recreation of the enthesis.
[0024] Typical embodiments of the present invention include an
implant for tendon-to-bone reattachment, the implant made of a
plurality of fibers cut from demineralized bone, the plurality of
fibers forming a contiguous shape having a peg portion and a sheet
portion. In particular, the peg portion has a tubular shape with a
closed end and an open end and is capable of being inserted
closed-end first into a cavity of a bone. The sheet portion has two
sides, and a first side is in contact with an area on the surface
of the bone adjacent the cavity. In typical embodiments, the second
side of the sheet portion contacts the tendon and the sheet portion
thereby forms an interface between the tendon and the bone.
[0025] In specific embodiments, the length of the peg portion of
the implant is of between about 10 to 50 millimeters (mm). The
diameter of the peg portion may be of between about 3 to 10 mm.
[0026] In other specific embodiments, the sheet portion of the
implant may be any shape so long as it fans out on the surface of
the bone and surrounds the open end of the cavity. For example, the
overall sheet portion surrounding the region of the peg portion may
be in a shape of or similar to a rectangular, a square, a circle,
or a non-perfect shape thereof and having a perimeter that forms a
rectangle, a square, a circle, or an irregular shape thereof.
Additionally, the sheet portion may not form a particular polygon
shape, but has a perimeter of straight sides. The straight sides
may each independently have a length of between 5 and 20 mm. In
example embodiments, in which the sheet portion has a circular
shape, the diameter of the circular shape may be of between about 5
and 20 mm. In additional or alternative embodiments, the sheet
portion may have a thickness of between about 0.5 to 5 mm.
[0027] The implant made of a plurality of fibers as described
herein having a peg portion and a sheet portion, may be made of
demineralized bone fibers (DBF), collagen, polymer, and/or
resorbable polymer fibers. Preferably, the implant is made of a
plurality of DBF fibers.
[0028] The inventive subject matter also includes a method of
augmenting reattachment of a tendon to a bone using the implant as
disclosed herein. The method includes placing a suture anchor into
the peg portion of the implant, optionally preparing a bleeding
bone bed on the bone, creating a cavity in the bone, placing the
peg portion of the implant into the cavity in the bone, screwing
the suture anchor into place, and using the sutures to
re-approximate and tie down the tendon to effect the reattachment
of the tendon to bone.
[0029] The inventive subject matter also includes a method for
making the presently disclosed implant. In typical embodiments, the
method for making the presently disclosed implant includes
dispersing a plurality of fibers with pressure (under pressure)
into a vented mold thereby draining the fluid from the mold. The
method may further include heating the plurality of fibers in the
mold. Heating of the plurality of fibers may occur at or between
35.degree. to 55.degree. or 45.degree. to 55.degree. C. In example
embodiments, the fibers (e.g., demineralized bone fibers) are
lyophilized.
[0030] The inventors also contemplated methods of augmenting a
tendon to bone reattachment procedure in which the implant as
disclosed herein is placed between the tendon and the bone.
[0031] Additional embodiments of the contemplated subject matter
include a method of facilitating the surgical placement of an
orthopedic bone implant wherein the method includes augmenting the
orthopedic bone implant with a peg portion. The orthopedic bone
implant may be an existing sheet implant known in the art. As such,
methods may include modifying the sheet form or modifying the
manufacture protocol of the sheet form to include a peg portion
attached thereto.
[0032] Aspects of the inventive subject matter include an augmented
implant wherein an implant (e.g., a sheet implant) is modified to
have a stabilizing portion. The stabilizing portion may increase
the effectiveness of sutures used to place the implant for the
needed surgical repair. Furthermore, the stabilizing portion may
increase the stability of the implant while the implant is being
surgically placed and/or tethered into place. For example, the
stabilizing portion may be a peg portion. The peg portion may be
solid or tubular (e.g., hollow) with an open and closed end.
BRIEF DESCRIPTION OF THE DRAWINGS
[0033] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication with color drawings will be provided by the Office upon
request and payment of the necessary fee.
[0034] FIG. 1 shows an implant for augmentation of screw fixation
and delivery device, according to embodiments of the present
invention where the implant 1 is placed in the tubular portion of
the delivery instrument 2 and is expelled from the device using the
plunger 3 where an optional protective cap 4 may be included and is
removed prior to use.
[0035] FIG. 2 shows a variant of the implant 1 wherein the front of
the cylinder has a domed shape 5 to facilitate insertion, according
to some embodiments of the present invention.
[0036] FIG. 3 shows a variant of the implant 1 wherein the rear of
the cylinder has a central depression 6 to facilitate insertion of
the screw centrally in the implant, according to some embodiments
of the present invention.
[0037] FIG. 4 shows a cylindrical mold 7 and plunger 8 designed to
produce cylindrical implants, according to some embodiments of the
present invention.
[0038] FIG. 5 shows a variant of the mold 7 of FIG. 4 wherein the
plunger 8 has a spike 9 that produces a central depression in the
implant to facilitate central screw insertion, according to some
embodiments of the present invention.
[0039] FIG. 6 shows a further variant of the mold 7 of FIG. 4
wherein the distal end of the cylindrical mold 7 has a domed
depression 11 to provide a domed implant, according to some
embodiments of the present invention.
[0040] FIG. 7 shows a mold 12 with semi cylindrical depressions 13.
DBF is wet laid into a mold and the implant is formed from two
conjoined semi cylindrical depressions. The implants 14 may be
stored in this manner in a flexible storage tray 15 and at the time
of surgery may be folded together to produce a cylindrical implant
16, according to some embodiments of the present invention.
[0041] FIG. 8 shows a sheet mold 17 and sheet 18 produced from it.
The thickness and density of the sheet are controlled by varying
the quantity of DBF used and the spacing between the lid and the
bottom of the mold, according to some embodiments of the present
invention.
[0042] FIG. 9 shows a sheet of DBF 19 formed onto the porous
surface of an implant 20, according to some embodiments of the
present invention.
[0043] FIG. 10 shows a hamstring graft 21 with a DBF sheet 22
sutured into the regions of the graft destined for the bone
tunnels, according to some embodiments of the present
invention.
[0044] FIG. 11 shows a sheet of DBF 22 placed between the tendon 23
and bone 24. Also shown are sutures 25a and suture anchors 25b used
to reattach the tendon, according to some embodiments of the
present invention.
[0045] FIG. 12 shows a DBF implant 26 formed in a shape that
surrounds the hip stem and forms an interface between the hip stem
27 and surrounding bone 28, according to some embodiments of the
present invention.
[0046] FIG. 13 shows a cross sectional view of a variant of the
implant for augmentation of screw fixation 1 wherein in addition to
the domed end 5 to aid insertion there is an expanded proximal
portion of the implant 29, according to some embodiments of the
present invention.
[0047] FIG. 14 shows a cross sectional view of a variant of the
implant for augmentation of screw fixation 1 wherein the implant is
of a narrower diameter at its distal end 30, according to some
embodiments of the present invention.
[0048] FIG. 15a shows a variant of the implant for augmentation of
screw fixation 31 wherein the implant is in the form of a
rectangular prism, according to some embodiments of the present
invention.
[0049] FIG. 15b shows a variant of the implant of the present
disclosure, where a central portion 32 is densified to provide it
with increased strength, according to some embodiments of the
present invention.
[0050] FIG. 15c shows a variant of the implant of the present
disclosure where the cross-section 33 is semi-circular, according
to some embodiments of the present invention.
[0051] FIG. 15d shows a variant of the implant of the present
disclosure where the rectangular prism is narrower at the center
34, according to some embodiments of the present invention.
[0052] FIG. 15e shows a variant of the implant of the present
disclosure where; the rectangular prism is both narrower at the
center 34 and possesses a semi-circular cross-section 33, according
to some embodiments of the present invention.
[0053] FIG. 15f shows a variant of the implant of the present
disclosure where a side view cross-section of a drill hole 35 with
an implant 31 inserted, the insertion being effected by use of a
pusher 36, where the implant is longer than is required to fit the
hole, according to some embodiments of the present invention.
[0054] FIG. 15g shows a side view cross-section of a drill hole 35
with an implant 31 of the present disclosure inserted, the
insertion being effected by use of a pusher 36, Where the implant
is the exact length that is required to fit the hole, according to
some embodiments of the present invention.
[0055] FIG. 15h is an end view of the implant of FIG. 15c looking
down the hole to show the implant forms a space-filling implant
when inserted, according to some embodiments of the present
invention.
[0056] FIG. 15i is a cross-sectional view of the implant of FIG.
15e in a tapered hole where the shape of the implant forms a
space-filling implant in the tapered hole, according to embodiments
of the present invention.
[0057] FIG. 16 shows a cross-section view of an apparatus for water
assisted injection molding of DBF fibers, where the DBF fibers 37
are loaded into a syringe 38, the distal end of the syringe is
fitted into an adapter 39, attached to which is a detachable mold
40, where the mold is tapered towards its distal end and has vents
41 along its length, and a removable vented end cap 42, and the
detachable mold is removed after DBF injection and placed into an
oven or lyophilizer for drying, according to some embodiments of
the present invention.
[0058] FIG. 17 shows a cross-section view of an apparatus for water
jet assisted injection molding of DBF fibers, where the DBF fibers
37 are loaded into a hopper 43, the hopper being attached to a
detachable mold 40, the mold tapered toward its distal end having
vents 41 along its length, and a removable vented end cap 42, where
the water jet 44 is activated to force the DBF from the hopper and
into the mold, and the detachable mold is removed after DBF
injection and placed into an oven or lyophilizer for drying,
according to some embodiments of the present invention.
[0059] FIG. 18 shows a cross-section view of a variant of the
apparatus shown in FIG. 16 that provides for manufacture of a
cannulated implant using the water assisted injection molding
process. The DBF fibers 37 are loaded into a syringe 38, the distal
end of the syringe is fitted into an adapter 39, attached to which
is a detachable mold 40, where the mold is tapered towards its
distal end and has vents 41 along its length, and a removable
vented end cap 43 that also serves to hold a guide wire 44.
[0060] FIG. 19 shows how the detachable mold of FIG. 18 is removed
after DBF injection and a cap 45 is placed on the proximal end of
the device locating and centralizing the guide wire. The mold is
then placed into an oven or lyophilizer for drying, according to
some embodiments of the present invention.
[0061] FIGS. 20a-20e show the steps in the surgical implantation
technique to create a cavity for implantation of a cannulated
implant. For the purpose of the demonstration a synthetic foam
analog 46 of osteoporotic bone is used (Sawbones Inc.). In FIG. 20a
a guide wire 47 is placed in the bone. In FIG. 20b a cannulated awl
48 is placed over the guide wire. In FIGS. 20c and 20d, the awl is
shown being pushed and turned into the bone to form a cavity 49 as
shown in FIG. 20e. In FIG. 20f, the awl is then removed and an
implant 50 is selected that corresponds to the size of the awl.
[0062] FIGS. 21a-21i show the steps of implant placement and screw
insertion. In FIG. 21a the implant 50 is shown being placed on the
guide wire 47. In FIGS. 21b and 21c the implant can be seen being
pushed into the cavity 49. FIG. 21d shows a cannulated pedicle
screw 51 with a cannulated driver 52 placed over the guide wire and
used to push the implant 50 into the cavity.
[0063] FIG. 21e shows an alternative method where the awl 48 is
used as the pusher. FIGS. 21f and 21g show the screw being inserted
into the bone. When the screw is fully inserted the driver 52 and
guide wire 47 are removed as is shown in FIG. 21h. While not part
of the procedure for the purposes of illustration in FIG. 21i the
screw has been removed allowing the placement of the implant 50 to
be seen.
[0064] FIG. 22 shows an implant 50 cross section. The implant has a
central cannulation 53. The body of the implant 54 is a truncated
cone that is narrower at the distal end. A flared top 55 at the
proximal end has a depression 56.
[0065] FIG. 23 shows the cross section of a non cannulated implant.
The body of the implant 54 is a truncated cone that is narrower at
the distal end. A flared top 55 at the proximal end has a
depression 56.
[0066] FIG. 24 shows the cross section of an implant of this
invention for use in ad augmentation. The implant is a truncated
cone 57 wherein the distal end is narrower than the proximal end.
The central cannulated region 58 is flared so that the opening at
the proximal end is greater than at the distal end.
[0067] FIGS. 25a-25e shows a device for use in ad augmentation. In
FIG. 25a the components 59 of the device are two sheets of DBF.
FIG. 25 b shows them slotted together to make a cruciate form 60.
FIG. 25c shows the four strands 61 of a hamstring graft positioned
within the cruciate device 60. Whipstitching the graft in
preparation for implantation serves to cause the sheet to conform
around the outside of the graft as shown in FIG. 25d and hold it in
place. One device is placed at each end of the graft as is shown in
FIG. 25e.
[0068] FIGS. 26a-26e show a device for use in ad augmentation. In
FIG. 26a the components 59 of the device that are two sheets of
DBF, one wider than the other. FIG. 26b shows them slotted together
to make a cruciate form 60. FIG. 26c shows the four strands 61 of a
hamstring graft positioned within the cruciate device 60.
Whipstitching the graft in preparation for implantation serves to
cause the sheet to conform around the outside of the graft as is
shown in FIG. 25d and hold it in place. One device is placed at
each end of the graft as is shown in FIG. 26e.
[0069] FIG. 27a shows a variant of the device fabricated from two
DBF sheets 62 and 63 that are shaped to wrap around the tendon (not
shown). FIG. 27b is a photograph of a device fabricated from a DBF
sheet and FIG. 27c is a variant using a single DBF sheet that can
be used with a two strand graft.
[0070] FIG. 28a shows a device for ad augmentation fabricated from
a DBF sheet 64 that has four holes 65. FIG. 27b shows a device for
ad augmentation fabricated from a DBF sheet 64 that has four holes
65 and four cut outs 66. The four strands 61 of the graft are
threaded through the holes prior to whipstitching to provide the
graft ready for implantation in FIG. 28c.
[0071] FIG. 29 shows the surgical use of the device of FIG. 24. The
device 57 is placed within the four strands 61 of a tendon graft
before being pulled into the tibial tunnel. An interference screw
67 is then inserted within the device.
[0072] FIGS. 30a-30d show a device to augment reattachment of
tendon to bone. The device 68 that is fabricated from demineralized
bone fibers is shown in FIG. 30a. The device has a "peg" 69 that is
intended to be placed in a hole in bone, a cavity 70 within that
peg that is designed to receive a suture anchor, and a sheet region
71 that is intended to sit between tendon and bone. In FIG. 30b a
dilator 72 is shown that is intended to create a defect in bone to
receive the device 68. The dilator has a depth mark 73 that
indicates the depth of hole to be made. FIG. 30c shows a suture
anchor 25b mounted on the driver 74 used to implant it. In FIG. 30d
the suture anchor has been introduced into the cavity 70 in the
device. Note that the suture anchor 25b cannot be seen in the FIG.
due to the device.
[0073] In FIG. 31a the bone 24 has been prepared to receive two
devices 68. Two holes 75 have been made in the bone. In FIG. 31b
the suture anchors 25b have been used to introduce the devices 68
into the bone and the suture 25a has been used to re-attach the
tendon 23 to the bone. The sheet region 71 of the device is sited
between the tendon 23 and bone 24.
DETAILED DESCRIPTION
[0074] Aspects of the embodiments of the present invention are
directed to an approach for augmenting bone repair and healing
using demineralized bone fiber (DBF), collagen, polymer, and/or
resorbable polymer fiber implants.
[0075] In some aspects, embodiments of the present invention
include fiber implants, methods of forming fiber implants, and kits
including suitably shaped and sized cylindrical fiber implants for
augmenting the fixation of screws in osteoporotic or otherwise
compromised bone. This approach includes a cylinder of
demineralized bone fibers (DBF.TM.) that may be inserted into a
hole in a bone in need of repair for the implant to be placed
together with and prior to the placement of a bone screw. The
cylinder is sized to be the same diameter as the screw hole. At the
time of surgery, the presence of the device increases the torque
required to insert the screw and increases the pull out force that
would be required to displace the screw. The additional benefit of
using the DBF material is that it is osteoinductive and will cause
an increase in local bone formation around the screw providing long
term enhancement of fixation. The DBF implant is placed into the
hole of the bone prior to insertion of the screw.
[0076] In other aspects, embodiments of the present invention
include DBF, collagen, polymer, and/or resorbable polymer fiber
implants, and methods forming DBF, collagen, polymer, and/or
resorbable polymer fibers implants, and kits including suitably
formed DBF, collagen, polymer, and/or resorbable polymer fiber
implants for use as an interface between the bone and the ligament
or tendon to be repaired. For example, a sheet of DBF may be used
in the bone tunnels of a soft tissue ligament replacement such as
an ad (anterior cruciate ligament) surgery where a hamstring or
tendon autograft is fixed into a bone tunnel. Additionally, a sheet
of DBF may also be used in a rotator cuff repair in which the DBF
sheet is placed onto the bone bed between the bone and the tendon
to be reattached.
[0077] As used herein "implant," "fiber implant," "implant of the
present disclosure," and like terms are used interchangeably to
refer to a suitably shaped fiber implant made using demineralized
bone fibers (DBF) as disclosed herein and disclosed in U.S. Pat.
Nos. 9,486,557 and 9,572,912, and WO 2016/123583, the entire
contents of all of which are incorporated herein by reference. For
example, as shown throughout the present disclosure, suitably
shaped DBF implant includes a sheet of DBF, cylinder-shaped, or
truncated cone forms of DBF.
[0078] Additionally, for collagen, polymer, and/or resorbable
polymer fiber implants are made following the methods disclosed
herein for DBF with a substitution or addition of the collagen,
polymer, and/or resorbable polymer fibers. While DBF fibers are
exemplified herein, these other fiber forms may also be used to
form the presently disclosed fiber implants.
[0079] Resorbable polymers are biocompatible polymers capable of
resorbing in the body and have a physical strength to form a fiber
or particle at room temperature. Non-limiting examples of
resorbable polymers include silk, collagen (including Types I to V
and mixtures thereof), and proteins comprising one or more of the
following amino acids: alanine, arginine, asparagine, aspartic
acid, cysteine, glutamine, glutamic acid, glycine, histidine,
isoleucine, lysine, methionine, phenylalanine, proline, serine,
threonine, tryptophan, tyrosine and valine; polysaccharides,
including alginate, amylose, carboxymethylcellulose, cellulose,
chitin, chitosan, cyclodextrin, dextran, dextrin, gelatin, gellan,
glucan, hemicellulose, hyaluronic acid, derivatized hyaluronic
acid, oxidized cellulose, pectin, pullulan, sepharose, xanthan and
xylan; resorbable polyesters, including resorbable polyesters made
from hydroxy acids (including resorbable polyesters like
poly(lactides), poly(glycolides), poly(lactide-co-glycolides),
poly(lactic acid), poly(glycolic acid), poly(lactic
acid-co-glycolic acid), poly(dioxanones), polycaprolactones and
polyesters with one or more of the following monomeric units:
glycolic, lactic; trimethylene carbonate, p-dioxanone, or
-caprolactone, and resorbable polyesters made from diols and
diacids; polycarbonates; tyrosine polycarbonates; polyamides
(including synthetic and natural polyamides, polypeptides, and
poly(amino acids)); polyesteramides; poly(alkylene alkylates);
polyethers (such as polyethylene glycol, PEG, and polyethylene
oxide, PEO); polyvinyl pyrrolidones or PVP; polyurethanes; poly
etheresters; polyacetals; poly cy ano acrylates; poly (oxy
ethylene)/poly (oxypropyl ene) copolymers; polyacetals, polyketals;
polyphosphates; (phosphorous-containing) polymers;
polyphosphoesters; polyalkylene oxalates; polyalkylene succinates;
poly(maleic acids); biocompatible copolymers (including block
copolymers or random copolymers); and hydrophilic or water soluble
polymers, such as polyethylene glycol, (PEG) or polyvinyl
pyrrolidone (PVP), with blocks of other biocompatible or
biodegradable polymers, for example, poly(lactide),
poly(lactide-co-glycolide), or polycaprolactone or combinations
thereof. Resorbable polymers also include cross-linked polymers,
and include, for example, cross-linked collagen, as well as
functionalized polymers. In some embodiments, resorbable polymers
are resorbable polyesters.
[0080] In further embodiments, the DBM, synthetic polymer,
collagen, or resorbable polymer fibers may be coated (e.g., at
least in part) with a calcium ion donor compound. Examples of
calcium ion donor compounds include calcium peroxide, calcium
ascorbate, calcium sulfate, calcium phosphate, calcium carbonate,
calcium chloride, and mixtures thereof.
[0081] The popularity of demineralized bone matrix (DBM)-based
products is based on the ability to induce bone formation through
expression of inherent non-collagenous proteins that stimulate some
cell types present at the graft site to differentiate into bone
forming cells. This induction of bone formation process is referred
to as "osteoinduction" and is due to the natural presence of bone
morphogenic proteins (BMPs). DBM also provides a scaffold for these
cells to populate and spread throughout in a process known as
"osteoconduction." Demineralized bone in the form of a fiber, known
as Demineralized Bone Fiber (DBF) has a physical form that has been
shown to optimize and enhance the osteoconductive performance of
DBM. In some embodiments of the present invention, a composition
and method of manufacture of DBF fibers is as disclosed in U.S.
Pat. Nos. 9,486,557 and 9,572,912, supra. When DBM or DBF is
combined with osteogenic cells that are capable of forming bone,
the three mechanisms of bone healing (e.g., osteoinduction,
osteoconduction, and osteogenesis) are combined.
[0082] In exemplary embodiments, the DBF implant is dried so that
the implant has sufficient rigidity to allow it to be pushed into a
pre formed hole. The DBF fibers may be easily formed into any of
the required implant shapes using molding or wet laying processes
prior to drying. Optionally a heating step may be utilized which
has been shown to impart even greater cohesion to formed DBF
implants without affecting the implant's osteoinductivity.
[0083] Variations and sophistications to the design include shaping
or doming of the distal end of the DBF implant to aid in insertion
of the DBF implant into the hole of the bone. An example of such a
design is exemplified in DBF implant 5 of FIG. 2. In some
embodiments, the proximal end of the DBF implant may also be flared
29 in FIG. 13. This feature may help prevent the implant from being
pushed too far into a drilled hole. It will also provide additional
DBF fibers at the cortex of the bone and may facilitate healing of
that region of the bone. Reformation of the cortex of the bone is
particularly important for pedicle screw fixation in spinal surgery
as toggling of the screw is the primary mode of loading and hence
failure, and the cortex provides the most resistance to this mode
of loading.
[0084] The implant may also be a non-uniform cylinder, i.e. a
truncated cone, such that the distal end 30, as shown in the
cross-sectional view in FIG. 14 is narrower than the proximal end
of the implant. The implant is placed into the hole prior to
insertion of the screw.
[0085] An implant in the shape of a rectangular prism 31 as shown
in FIG. 15a may also be used for augmentation of screw fixation.
The rectangular prisms may be formed individually or may be cut
from a sheet of material 18 that has been formed in a mold. A
simple rod 36 may be used to aid insertion of the implant into a
drill hole. Densification of an area 32 of the implant may be done
to provide a strengthened area to aid insertion. An implant 31 in
the shape of a rectangular prism with a semi-circular cross section
33 allows for more effective filling of the hole. This can be seen
in FIG. 15h which is a top view of an implant 31 with a
semi-circular cross section 33 placed in a drill hole 35. The
implant is placed into the hole prior to insertion of the
screw.
[0086] In some instances, it will be desired to place an implant in
the hole created when a screw is removed from bone, such as in a
revision procedure, or in a hole created by an awl. In these cases
the distal end of the hole will generally be a smaller diameter
than the proximal end. An implant with a shape such as is shown in
FIG. 15d or 15) is designed to be used in this instance. The
implant is placed into the hole prior to insertion of the
screw.
[0087] While implants according to embodiments of the present
invention may be easily placed into drilled holes by hand, it is
envisaged that in some instances it may be desired to have the
implant that is provided to the surgeon to be pre-loaded into a
syringe like device implant shown in FIG. 1. As is shown in this
FIG., the implant 1 is held in the body of the syringe 2. In this
embodiment, the implant includes a removable cap 4 to maintain the
implant in place during storage and transportation, and may
optionally have a luer fitting to allow pre hydration of the
implant. For implant delivery, the distal end of the syringe is
placed over the drill hole and the plunger 3 used to expel the
implant. A reusable implant delivery system may also be used.
[0088] The hole to receive the implant may be formed by drilling,
tapping, or by use of an awl, or may exist through the removal of a
screw.
[0089] In a variant of an implant according to some embodiments of
the present invention, the implant is provided with a hole through
its length such that the implant may be delivered over a guide
wire.
[0090] When pushing the proximal end of the implant into the hole
or cavity in the bone there is a buckling force caused by friction
of the implant against the bone. Several factors may be
incorporated into the design to accommodate this. Firstly, the
implant may be in the form of a truncated cone with the distal end
narrower than the proximal end as is shown in FIGS. 22 and 23.
Secondly, an awl is used to provide the cavity in the bone that is
itself in the overall shape of a truncated cone such that the
cavity produced is the same dimensions as the implant. Thirdly an
external device may be used to provide support and resistance to
buckling on insertion. This may be an open-ended syringe, as
disclosed above where the barrel of the syringe provides support to
the implant, or it may be by placing the cannulated implant over a
guide wire.
[0091] It may also be desired to prevent the implant from being
displaced too deeply into the bone. In the designs shown in FIGS.
22 and 23 the flared top 53 acts to prevent this occurrence.
[0092] The surgical technique for using an implant of this
invention is outlined in FIGS. 20 and 21. A synthetic analog of
osteoporotic bone 46 produced by Sawbones, Inc. is accepted by the
FDA and others as a surrogate for osteoporotic bone. A guide wire
47 is placed in the bone. A shown in FIG. 20b a cannulated awl 48
is then placed over the guide wire. The awl is dimensional the same
as the implant that is to be used. A further benefit of using an
awl is that it does not remove bone tissue, but rather pushes it
laterally and forms a densified bone layer that in itself will aid
fixation. In FIGS. 20c and d the awl is shown being pushed and
turned into the bone to form a cavity 49 as shown in FIG. 20e. The
awl is then removed and an implant 50 is selected that corresponds
to the size of the awl. Where the implant has a flared end the awl
may also have a corresponding feature.
[0093] FIG. 21 shows the steps of implant placement and screw
insertion. In FIG. 21a the implant 50 is shown being placed on the
guide wire 47. In FIGS. 21b and c the implant can be seen being
pushed into the cavity 49. FIG. 21d shows a cannulated pedicle
screw 51 with a cannulated driver 52 placed over the guide wire and
used to push the implant 50 into the cavity. FIG. 21e shows an
alternative method where the awl 48 is used as the pusher. FIGS.
21f and g show the screw being inserted into the bone. The guide
wire serves an additional purpose in that it helps maintain the
screw trajectory in the center of the implant so that DBF is pushed
laterally around the whole screw circumference.
[0094] When the screw is fully inserted the driver 52 and guide
wire 47 are removed as is shown in FIG. 21h.
[0095] In FIG. 21i the screw has been removed allowing the
placement of the implant 50 to be seen. As desired the DBF fibers
are displaced laterally by the screw as it is inserted. There is a
further advantage of truncated cone and flared end in that it helps
to further resist any downward migration of the implant as the
screw is inserted.
[0096] Another beneficial aspect of the flared design is that a
quantity of DBF can be positioned on the surface of the bone. This
is the region in for example, the pedicle, where cortical bone is
removed to gain access to the pedicle. In use the loading on a
pedicle screw tends to "toggle" the screw and loosen it. The
primary area of bone that can resist this motion is the cortical
surface so the placement of DBF where it can help to stimulate
reformation of the cortex is beneficial. If desired the awl could
be designed so that the entire flared portion of the implant is
positioned on the bone surface.
[0097] The implant can be the same length as the screw that it is
intended to be used with or it may be shorter.
[0098] Where the procedure is desired to be done using a guide wire
the device, awl or drill, screw and screwdriver will all be
cannulated to accommodate use over a guide wire.
[0099] The implant may be supplied as a kit with a guide wire and
awl. The kit may also include screws. The guide wire and awl may be
supplied as sterile disposable single use items or may be designed
to be re-usable.
[0100] The implant is dependent on having some rigidity to enable
it to be inserted in the bone and as such this is best achieved by
using the DBF in a dry state. Once in place in the bone the fibers
will hydrate. The effect of this will be to cause them to swell,
providing additional fixation.
[0101] In other embodiments of the present invention, with
reference to FIG. 18, DBF in the form of a thin sheet 18 may also
be used to act as an interface between an implant and surrounding
bone. The DBF sheet will facilitate conformity of the implant to
the surrounding bone and will subsequently, through its
osteoinductive nature, stimulate bone formation and integration of
the surrounding tissue with the implant.
[0102] DBF in the form of a hydrated thin sheet may also be pressed
onto the surface of a screw or implant prior to implantation for
similar effect.
[0103] DBF in the form of a thin sheet may also be used to
stimulate bone formation in the bone tunnels of a soft tissue
ligament replacement such as an ad (anterior cruciate ligament)
surgery where a hamstring or tendon autograft is fixed into a bone
tunnel. In this usage, as shown in FIG. 10 a sheet of DBF 22 may be
sutured onto the hamstring graft 21 prior to implantation into the
patient with the DBF positioned so that it is in tunnel portion of
the graft, and may optionally be hydrated to aid its conformity.
The osteoinductive nature of the DBF material will stimulate bone
to graft healing. The sheet may be simply wrapped around the
outside of the hamstring or tendon bundle or may be incorporated in
a way that provides DBF between the individual tendons. Suture may
be used to hold the DBF sheet in place and may be whipstitched in
place during the existing graft preparation step.
[0104] It is desired to stimulate bone formation throughout the
graft within the bone tunnel as well as stimulate the formation of
the tendon bone interface. To this end it is desirable to have DBF
within the strands of the graft. One means of achieving this is to
use two pieces of the DBF sheet and place slots in them so that
they can be slotted together to form a cruciate shape. Examples of
how this could be done are shown in FIGS. 25, 26 and 27. While the
most common graft uses four strands the design in FIG. 27 c shows
how simply the design can be adapted for a two strand graft by
using a single sheet of DBF.
[0105] An alternative format of the device is to use a sheet of DBF
and cut or punch holes in it that the strands of the graft can be
threaded though as is shown in FIG. 28a and FIG. 28b.
[0106] As an alternative method of augmentation that is
particularly suited to the tibial tunnel a cone shaped implant 57
such as is shown in FIG. 24 may be placed within the four strands
of the graft, as is shown in FIG. 29. The interference screw is
then inserted inside the implant and screwed into place to affect
fixation of the tendon
[0107] Augmentation of other tendon and bone interfaces may also be
effected by use of sheets of DBF. FIG. 11 is a diagram showing a
rotator cuff repair wherein the DBF sheet 22 is placed onto the
bone bed between the bone 24 and the tendon to be reattached 23.
The nature of the DBF sheet is such that conventional suture anchor
fixation techniques do not need to be modified. In FIG. 11 the
repair may be seen to be affixed using the sutures 25a together
with the suture anchors 25b.
[0108] Rotator cuff repair is generally done as an arthroscopic
procedure and so the joint is inflated with saline to aid
visualization. There are a number of patch products used for
reinforcement of the tendon, and while this is not the intended
application for the DBF sheet in the aforementioned example, our
sheet will be subject to similar difficulties in use that all patch
products have, namely that their buoyancy leads to them tending to
float around in the joint. Manipulation of these sheets
arthroscopically is extremely difficult adding time and complexity
to the surgery. This can exclude some surgeons from being able to
use the products due to the degree of difficulty. In some
instances, sophisticated, (i.e. complex and expensive), ancillary
instruments are developed in an attempt to make the use of sheet
products easier.
[0109] Aspects of the inventive subject matter include an augmented
implant wherein an implant (e.g., a sheet implant) is modified to
have a stabilizing portion. The stabilizing portion may increase
the effectiveness of sutures used to place the implant for the
needed surgical repair. Furthermore, the stabilizing portion may
increase the stability of the implant while the implant is being
surgically placed and/or tethered into place. For example, the
stabilizing portion may be a peg portion. The peg portion may be
solid or tubular (e.g., hollow) with an open and closed end.
[0110] Accordingly, the inventors of the presently disclosed
subject matter have discovered an advantageous implant that is at
once capable of: 1) serving as a patch for the bone site to be
repaired. 2) augmenting the effectiveness of the suture anchor, and
3) self-stablizing during surgery unlike other implants.
Accordingly, aspects of embodiments of the present invention are
directed to a means of improving the fixation of implants and
tissue to bone through the use of an implant, which may, for
example, be composed of fibers of demineralized bone and formed
into an appropriate shape. In particular, the implant made of a
plurality of fibers has peg portion and sheet portion.
[0111] The implant device 68 shown in FIG. 30a overcomes the
problems associated with the manipulation of sheet-like devices in
the joint. The sheet portion 71 of the device has a "peg" 69 that
is formed onto it. The peg has a cavity 70 that receives a suture
anchor 25b. The surgical technique by which these implants are used
is that a dilator 72 or other instrument is used to form a cavity.
A mark 73 on the dilator serves to allow the surgeon to get the
desired depth of cavity. Suture anchors 25b for use in arthroscopic
surgery are generally supplied pre-loaded with suture and attached
to an insertion driver 74. The peg 69 on the device is sized to
match the dimensions of the cavity formed using the dilator and the
cavity 70 in the device is sized to receive the suture anchor 25b.
The suture anchor is inserted into the cavity 70 and turned
slightly to engage the threads of the anchor into the device. This
served to lock the device onto the suture anchor. The suture anchor
driver can then be used to manipulate the peg part of the device
into the cavity in the bone.
[0112] The sheet or top portion of the device is sized so that when
multiple suture anchors are used that the multiple devices that are
used form a contiguous sheet at the tendon bone interface. Thus, if
for example the surgeon desired a 10 mm spacing between suture
anchors then the device selected would be 10 mm wide or would be
trimmed to 10 mm wide so that adjacent device/suture anchor
combinations would form a contiguous sheet. Similarly, if a double
row fixation technique were to be employed where there were two
rows of suture anchors then the dimension of the sheet portion of
the device would be sized appropriately such that a non-overlapped
contiguous sheet were formed.
[0113] FIG. 31b shows the first steps in the surgical technique.
The surface of the bone where the tendon is to be re-attached 75 is
treated with a burr or similar to form a bleeding bone bed to
maximize healing potential, as is normal practice. A dilator, or
similar (not shown) is used to produce cavities 76 to receive the
device 68 and suture anchor. As described above the suture anchor
is inserted into the device 68 and rotated to engage the anchor
threads into the device and lock the two together. The device is
inserted into the cavity 76 and pushed down to fully seat it. The
suture anchor is then screwed in. The anchor driver is removed
leaving the sutures ready to be used. Additional anchors and
devices are inserted, as required by the size of the tear being
repaired. The device is held in place by the suture anchor and the
completion of the surgery requires no additional manipulation of
the device. To complete the repair, the current procedure of
passing the sutures through the tendon and using them to
reapproximate the tissue before knot tying is done. The device is
sandwiched between the tendon at the bone where it can have the
desired effect of stimulating an improved enthesis
regeneration.
[0114] The preferred embodiment of this device is dried or
lyophilized. In this form the device is stiff and insertion into
the cavity is easiest.
[0115] An additional benefit of the device 68 is that the peg
portion of the device serves to augment the fixation strength of
the suture anchor. This is especially important when the patient's
bone quality is poor. It may also allow the surgeon to use a
smaller diameter suture anchor.
[0116] The peg portion of the device 68 is designed to be
compatible with the suture anchor it is to be used with. As such
the length of the peg corresponds to the depth of the cavity
required for the suture anchor and may vary from 10 to 50 mm.
Similarly, the diameter of the peg corresponds to the diameter of
cavity required for the suture anchor and may vary from 3 to 10
mm.
[0117] The sheet portion 71 of the device is sized such that when a
multitude of suture anchors are used that the bone bed 76 is fully
covered. This may be achieved by the surgeon trimming devices to
the required size prior to use, or by selection of the appropriate
size from an available range of product sizes. The sheet portion
may be rectangular, square or round. For square and rectangular
devices the side dimensions will vary from 5 to 20 mm. For round
devices the sheet portion will be 5 to 20 mm in diameter. The
thickness of the sheet portion of the device will vary from 0.5 mm
to 5 mm.
[0118] By using the suture anchor as the delivery device for the
implant the need for additional instruments is avoided. The design,
by using the anchor hole to provide initial fixation of the device,
provides a very simple means of introduction of a sheet device, and
of holding it in the desired place without the need for any
additional instruments, or additional portals into the joint.
[0119] By sizing the top portion, or sheet, of the device to be
compatible with the spacing used between suture anchors the need
for multiple sizes of device is avoided. This additionally means
that the waste associated with cutting larger sheet implants to the
desired size is avoided.
[0120] While this modular approach to covering the enthesis is
preferred, if desired a larger sheet implant could be provided that
had one or two pegs.
[0121] While the examples given for use of this design were for
rotator cuff repair it will be understood by one skilled in the art
that the applicability is more general than this and is applicable
to any instance of tendon to bone reattachment or repair, or any
instance where a sheet implant needs to be held in place during
surgery. Accordingly, the inventors further contemplate augmenting
any sheet implant with a peg portion to thereby facilitate the
surgical placement of the implant. It is contemplated that any
existing sheet implant may be improved by modifying an already
manufactured sheet implant or by modifying the manufacturing
protocols of the existing sheet implant to incorporate a peg
portion to produce an implant having improved stability during
surgical placement.
[0122] In some embodiments of the present invention, a DBF sheet
may be used for augmentation of bone-to-bone repair either in a
primary fracture repair or in a procedure to remedy a non-union. In
these instances, the DBF sheet will form a malleable interface
between the two (or more) bone fragments.
[0123] A DBF sheet may also be wrapped around the periosteum to
hold bone fragments or graft in place in traumatic fractures and
may act as a periosteum substitute. The osteoinductive and
osteoconductive nature of the DBF sheet will facilitate
healing.
[0124] In many joint replacements a stem is placed into a cavity
created in the intramedullary canal. It is often desired to enhance
the integration of implants such as total hip or shoulder
replacements to the surrounding bone. DBF may be formed into a
sheath 26 that conforms to the shape of the implant stem 27. The
DBF may then provide for augmentation, or stimulation of fixation,
of the stem to the surrounding bone.
[0125] A further issue that may occur is that, particularly in the
case of revision surgery, there is insufficient bone and the
surgeon may require the use of bone graft. In these instances, the
DBF sheath may be provided in a range of thicknesses up to several
mm in thickness to provide for use as a bone graft substitute.
[0126] In some embodiments of the present invention, the sheet form
of DBF may be used to augment the fixation of tibial tray and
acetabular cup components of joint replacements. In this latter
instance the sheet may be molded into a cup shape.
[0127] In some embodiments of the present invention, the DBF used
in an implant uses bone that has had the mineral component removed
by a demineralization process that renders the graft malleable and
not hard. The bone is then further formed into fibers by cutting
along the long axis such that the collagen fibers within it are
maintained in their natural fibrous form, as disclosed in U.S. Pat.
Nos. 9,486,557 and 9,572,912, supra. This material may then be
placed into tubes to form the implant device and to facilitate
delivery into the screw hole.
[0128] A number of methods of forming cylindrical implants from DBF
are also disclosed in WO 2016/123583, the entire content of which
is herein incorporated by reference.
[0129] In some embodiments, the methods for making the bone fibers
include demineralizing whole bone and subsequently cutting the
demineralized bone in a direction parallel to the orientation of
collagen fibers within the demineralized bone to form elongated
bone fibers. The bone material of the present invention is derived
from human (allograft) or animal (xenograft) cortical bone and is
processed in such a manner to provide grafts of high utility based
on the controlled geometry of the bone fibers. For veterinary
applications bone from the same species. e.g., canine for canine
patients (allograft) may be used as well as bone from other species
(xenograft). It will be obvious to one skilled in the art that
fibers other than demineralized bone fibers may be utilized to make
a bone graft of this invention. Such fibers may be made from
resorbable polymers or bioactive glasses or mixtures thereof, and
may be used in place of or as an additive to the demineralized bone
fibers (DBF). The methods of preparation of the graft provide
improved efficiency and uniformity with reproducible results and
decreased requirements for equipment and resulting costs. The
implant device forms according to some embodiments of the present
invention do not require the addition of exogenous materials to
maintain the form of the graft. These improved characteristics will
be apparent to one skilled in the art based upon the present
disclosure.
[0130] The fibers need to have greater than a minimum length to be
able to function effectively. If they are too short, they will not
entangle to form a cohesive dry implant. Also to prevent movement
in the cavity post implantation, and after screw placement, they
need to be longer than the pitch of the screw thread so that the
screw holds them in place. The minimum length cannot be precisely
defined but is approximately 15 mm (e.g., between 10 and 20 mm).
Fibers up to 4 cm in length have sufficient length to provide
entanglement and are preferably 500 to 1500 microns in width and 50
to 300 microns thick.
[0131] It is also important to a number of the applications that
the DBF can be dried to render a stiffer implant at the time of
implantation.
[0132] A further benefit of the DBF fibers is their ability to be
processed to form an implant that retains its integrity when
wet.
Processing of Fibers.
[0133] Processing of the demineralized bone fibers, synthetic
polymer fibers, collagen fibers, or resorbable polymer fibers to
produce a desired shape or form of the fibers may be performed
using any suitable method. Processing of specifically demineralized
bone fibers may be performed using any suitable method as disclosed
herein. To make some of these forms, the bone fibers may be
collected, ideally in their hydrated state, and compressed using
pressure molds, the pressure being sufficient to form the required
shape but not so high as to lose the porosity of the fibrous
structure. In some embodiments, the bone fibers are formed using a
wet lay technique as is well understood by those skilled in the art
of nonwoven or paper manufacture. Using a wet lay technique, the
cut bone fibers are suspended in an aqueous solution to form a bone
fiber slurry. Any suitable biocompatible aqueous solution may be
used. Non-limiting examples of biocompatible aqueous solutions
include: water, saline, and/or solutions including salts such as
phosphate buffered saline (PBS), Ringer's solution, Lactated
Ringer's solution, and saline with 5% dextrose. In some embodiments
of the present invention, cut fibers are placed into saline to
create a slurry of entangled bone fibers. The bone fiber slurry is
suspended over a mesh screen (having holes) and the saline is
drained resulting in a wet lay process, such that a sheet of
demineralized bone fibers is formed on the mesh screen. The screen
is contoured to provide a three-dimensional shape to the screen
such that cylindrical pellets may be directly produced, or is flat
so that a sheet is produced. The resulting devices may be then
dried using heat and/or vacuum or other means such as
lyophilization (freeze-drying). In some embodiments, prior to
drying, the sheet is placed in a mold and compressed to a defined
thickness and shape, followed by drying. As discussed herein,
density, porosity and overall dimensions of the resulting product
may be controlled using various molds and techniques.
[0134] Hydrated fibers may also be simply placed into a cylindrical
mold cavity and lightly compressed using a plunger or push rod such
as is shown in FIGS. 4, 5 and 6. In these variants features are
provided to modify the profile of the two ends of the cylindrical
mold. A set amount of fiber is introduced into a cylindrical mold
and the plunger used to compress the fibers to the required density
through control of the depth that the plunger is pushed. Where a
plunger has a spike on it, such as is shown in 6 of FIG. 9 the
spike may be designed to form a depression, a partial hole, or a
hole through the length of the implant. In this latter instance the
implant will be in the form of a tube.
[0135] In some embodiments a vacuum oven is used, whereby the
application of vacuum removes moisture and dries the implant.
[0136] In some embodiments the heating step is undertaken by
placing the implant in contact with a metal or other high
heat-conductivity surface such that the degree of
annealing/crosslinking is enhanced at that surface.
[0137] In other embodiments, the bone fibers are further processed
in a second drying step that may include vacuum drying and/or
lyophilization.
[0138] In some embodiments the amount of compression, heating, and
drying can be tailored to modify the rehydration and re-expansion
rates. For example, with no heating the rehydration is very fast
whereas heating at or between 35.degree. to 55.degree. or
45.degree. to 55.degree. C. for approximately one hour causes very
slow re-hydration and re-expansion. In other aspects, the heating
may occur at any of 35.degree., 36.degree., 37.degree., 38.degree.,
39.degree., 40.degree., 41.degree., 42.degree., 43.degree.,
44.degree., 45.degree., 46.degree., 47.degree., 48.degree.,
49.degree., 50.degree., 51.degree., 52.degree., 53.degree.,
54.degree., or 55.degree. C. By altering these processes, bone
fiber compositions as disclosed herein may retain their
manufactured shape during packaging, shipment, unpacking and
placement into the graft site, but after placement into the graft
site the DBF will begin to absorb moisture rapidly (within 30
seconds or less) and may be completely re-hydrated/re-expanded
within approximately 2 minutes, preferably being completely
re-hydrated/re-expanded within 30 seconds.
[0139] In other embodiments the bone fibers may retain some
moisture and will be placed in moisture impervious packaging.
Furthermore, the dried and molded bone fiber implant may be
sterilized after packaging. Sterilization of the implant may be
carried out using any suitable method. For example, sterilization
may be carried out by electron beam or gamma beam. Alternatively,
aseptic manufacture may be used to avoid the need for terminal
sterilization.
[0140] In other embodiments, the inventive subject matter also
includes a simple mold of the sort shown in FIG. 8 may be used to
make DBF sheets of 0.5 mm to 5 mm thick, where the mold lid may be
placed on the mold 17 (the mold having holes for drainage of the
liquid in the DBF slurry) where the lid is in contact with the DBF
after the DBF has been wet laid and may define the degree of
compression of the DBF and hence the density of the sheet.
[0141] A DBF sheet that is dried will have a low wet strength when
rehydrated and improvement to the DBF sheet wet strength may be
affected by placing the mold in an oven at 45-55.degree. C. and
heat treating the sheet for up to 2 hours.
[0142] In some embodiments, bone fiber pellets are formed by adding
wet fibers directly into a cylindrical mold. An example of a
cylindrical mold is a metal tube as is shown in FIG. 4. A bone
fiber pellet shape is useful as it may be delivered to a graft site
using a cannula as commonly used for minimally invasive surgery.
The bone fiber pellets are capable of passing through a tube. A
cylindrical mold is loaded with the fiber. A tamp is used to apply
some compression to the fibers. In some embodiments, a fiber loaded
cylindrical mold is dried by heat, vacuum, and/or lyophilization.
After drying, the bone fiber implant becomes more cohesive and
shrinks to a reduced volume. After drying, the bone fiber pellets
may be easily expelled out of the mold due to the shrinkage that
occurs upon drying.
[0143] While wet lay techniques may be used for the manufacture of
different shapes from the bone fibers, it will be recognized that
any other molding or forming technique used with textile fibers
could be used. Fibers with and without excipients may be directly
molded using compression into any shape. In some embodiments,
excipients may be selected that enhance the lubricity of the
implant facilitating delivery and further reducing and friction or
binding during this procedure.
[0144] Long cylindrical implants may not be easily produced using a
conventional wet lay process. As an alternative method, implants
may be wet laid into a mold 12 with two conjoined semi cylindrical
depressions having drainage holes throughout as shown in FIG. 7.
The implants 14 may be stored in this manner in a flexible storage
tray 15 and at the time of surgery may be folded together to
produce a cylindrical implant 16.
[0145] Alternatively, semi cylinder implants produced in a mold
such as shown in FIG. 7 may be folded together post wet lay and
prior to the heat treatment step. At this time the two halves of
the cylinder will become entangled and bonded to each other.
[0146] Alternatively implants for augmentation of screw fixation
may be formed in two halves, such that the implant is folded about
the part that becomes the implant's distal end. A selection of such
designs are shown in FIGS. 15a-15i. The simplest format is a
rectangular prism 31. Variants are shown as follows: in FIG. 15b
where a central portion 32 is densified to provide it with
increased strength; in FIG. 15c where the cross-section 33 is
semi-circular; in FIG. 15d where the rectangular prism is narrower
at the center 34; and FIG. 15e where the rectangular prism is both
narrower at the center 34 and possesses a semi-circular
cross-section 33. FIG. 15f shows a side view cross-section of a
drill hole 35 with an implant 31 inserted, the insertion being
effected by use of a pusher 36. The implant is longer than is
required to fit the hole. FIG. 15g shows a side view cross-section
of a drill hole 35 with an implant 31 inserted, the insertion being
effected by use of a pusher 36 in which the implant 31 is the exact
length or about the length necessary to fit in the hole without
protruding out of the hole. Additionally, FIG. 15h is an end view
looking down the hole to show that the implant shown in FIG. 15c
forms a space-filling implant when inserted into the hole. And FIG.
15i is a cross-sectional view of the implant of FIG. 15e inserted
into a tapered hole where the shape of the implant is designed to
be space-filling in a tapered hole.
[0147] With continued reference to FIGS. 15a-15i, implants of these
designs may be fabricated using a wet lay method with a mold that
has depressions that define the required implant dimensions. The
DBF may be heated to a temperature of between 40.degree. and
53.degree. C. for 30 to 150 minutes to dry the implant and to
improve the cohesion of the fibers. After drying the individual
implants are cut out of the wet lay mold.
[0148] Using the implant designs according to embodiments of the
present invention allows for facilitated insertion of the implant
into holes by use of a pusher that acts upon the fold of the
implant, as shown, for example in FIG. 15b, 32.
[0149] There are particular difficulties that are encountered when
trying to make implants of the size and shape required to be used
in augmentation of screw fixation in orthopaedic and spine surgery.
The desired or required implant dimensions are approximately 2 to 7
mm diameter and 1 to 7 cm long. To enable the implant to have
sufficient mechanical integrity and for the implant to be
implantable, the DBF fibers must be of a sufficient size to provide
a cohesive implant. The currently available DBF are approximately 4
cm long and 500 to 1000 microns wide are able to provide the
mechanical integrity, however the fiber size provides a difficulty
in processing the DBF into the required sizes using the
heretofore-identified manufacturing methods. This problem is
exacerbated when the implant is less than approximately 5 mm in
diameter and is required to be longer than 1.5 cm. The fabrication
of the implant of Example 1 below, while possible, was an extremely
time consuming and difficult process, and is not conducive to an
efficient manufacturing process. Furthermore, molding parts of the
designs shown in FIGS. 15a-15i require that the wet laid DBF is wet
laid into the grooves of the mold rather than across them. If the
fibers cross from one implant cavity to another then the fiber will
be cut when the part is removed from the mold. If this occurs for
too many fibers, then the cohesive strength of the part will be
lost. For these reasons, there is a size of approximately 5 mm
width, below which implants cannot be produced using this
methodology.
[0150] The wet lay process was originally developed for use in
paper making and textiles where the fibers are processed to make a
two-dimensional sheet like product. As the fluid drains the fibers
are laid onto the surface of the mold and as such are in a plane
that is generally parallel to the plane of the sheet being
produced. While this process can accommodate some undulations and
be used to make shapes like egg cartons it is wholly unsuitable for
the fabrication of cylindrical shapes.
[0151] According to embodiments of the present invention, by
dispersing fibers in an excess of fluid, the fluid and fibers may
be directed into molds of small diameter and long length. Implants
that are about 2 to about 5 mm in diameter and about 4 to 5 cm in
length have a volume of 0.15 cm.sup.3 up to 10.0 cm.sup.3.
Typically, the volume of the implant is about 0.15 cm.sup.3 up to
2.0 cm.sup.3.
[0152] Additionally, the length of the implant may be of between 2
cm in length up to 10 cm in length depending on the need of the
bone repair site. The length of the implant may be of between 3 cm
and 10 cm in length, 4 cm and 10 cm in length, 4 cm and 9 cm in
length, 4 cm and 8 cm in length, 4 cm and 7 cm in length, 4 cm and
6 cm in length, or 4 cm and 5 cm in length. For receiving and
fixing a bone screw, the implant (e.g., 31 of FIG. 15i, or 68 of
FIGS. 30a and 30d), may have a length corresponding to the length
of the bone screw. Accordingly, the length of the implant having a
cone, tubular, or cannulated shape may have a length suitable for
receiving a bone screw or any bone repair material including
additional demineralized bone fibers (DBF).
[0153] The required mass of DBF to fill those molds is
approximately 0.15 gram to 1 gram and may be dispersed in about 20
mls of fluid in a syringe, in a ratio of fibers to fluid as
disclosed herein. Dispersion of the fibers in fluid into the molds
may be by injection pressure or by vacuum as well as gravity as
needed. Any suitable fluid buffer may be used. For example,
phosphate buffered saline (PBS) may be used for dispersion of the
fibers as well as water or any biocompatible buffer or liquid.
[0154] In contrast to conventional methods of fabrication, rather
than rely on gravitational flow, an elevated pressure is applied to
the dilute fiber and fluid dispersion. This forces the fibers to
flow down narrow diameter structures rather than form an entangled
clump at the entrance to the mold cavity. Because the fibers are
dispersed, they do not compact when introduced into the mold.
Accordingly, the slurry suspension of fibers is advantageously
introduced and place in the mold because the fiber suspension is
injected or pushed into the mold at a rate greater than a
gravitational flow, but not so much pressure/force that the fibers
clump or compact. For example, a 15 ml slurry of a fiber suspension
having a ratio as disclosed herein is introduced into a mold in
about 1 to 5 seconds. As such, the slurry of fibers are placed or
provided into the mold at a rate from about 3 mls/second up to 15
mls/second.
[0155] FIG. 16 depicts an apparatus for water- or fluid-assisted
injection molding of DBF fibers. The required mass of DBF fibers 37
are loaded into a syringe 38. A suitable fluid (e.g., water,
saline, or a buffered saline including phosphate buffered saline
(PBS) is then added to the syringe. The distal end of the syringe
is then fitted into an adapter 39 to which a detachable mold 40 is
attached. The mold renders the required dimensions of the implant
to be made, and the mold may be cylindrical, ribbed, and/or
tapered. As with conventional injection molding, the cylinder will
have a small taper or draft to allow removal of the molded part.
The mold is tapered towards its distal end and has vents 41 along
its length, and a removable vented end cap 42 to allow for the
fluid to egress out of the DBF mixture. The detachable mold is
removed after DBF injection and placed into an oven or lyophilizer
for drying. Multiple molds may be used with one adapter and syringe
to allow multiple parts to be fabricated.
[0156] In some embodiments of the present invention, the ratio of
fluid (e.g., saline) to DBF may be about 3 mls fluid to 1 gram DBF.
In other embodiments, the ratio of fluid to DBF is about 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, 30, 40, 41,42, 43, 44, 45, 46, 47, 48, 49,
or 50 mls fluid to 1 gram of DBF. In still other embodiments, the
ratio of fluid to DBF is less than about 200 mls fluid to 1 gram
DBF. Advantageously, a ratio of fluid to DBF being in the range of
between about 3 to 200 mls fluid to 1 gram DBF, 3 to 150 mls, 3 to
100 mls, 3 to 50 mls, 3 to 20 mls, or 3 to 10 mls all provide
enough fluid to hydrate the DBF to facilitate shaping and forming
of the DBF implant into the desired shape while also allowing for
complete removal of the fluid to produce a dry DBF implant.
[0157] In some embodiments of the present invention, water jet
assisted injection molding of DBF fibers is used. As shown in FIG.
17, the DBF fibers 37 are loaded into the hopper 43. The hopper is
attached to a detachable mold 40, and the mold is tapered towards
its distal end and has vents 41 along its length, and a removable
vented end cap 42. A hand operated water jet 44 is activated to
force the DBF from the hopper and into the mold. The detachable
mold is removed after DBF injection and placed into an oven or
lyophilizer for drying.
[0158] With reference to FIGS. 30a and 30d, the disclosed water
assisted injection molding process may also be used to make the DBF
implants such as the screw fixation device 68.
[0159] In more specific embodiments, the nozzle of the water jet is
of between about 0.1 to 1 cm in diameter. Typically, the nozzle
diameter is of between about 1 mm to 5 mm in diameter, and more
typically, the nozzle diameter is of between about 2 mm to 4 mm in
diameter. The fluid flow rate may be about 1 ml/minute, 30 ml per
minute, or preferably up to about 1000 ml per minute.
[0160] The skilled person may easily envisage an apparatus with
multiple funnels leading to multiple molds in a manner analogous to
multi-cavity injection molds as used to fabricate injection molded
polymer parts.
[0161] The implants of the present disclosure in their dry state
may be inserted into a cavity, screw hold, awl hole, or drill hole.
Additionally, the implants of the present disclosure may be housed
in a syringe or syringe-like insertion device. With the implant in
a syringe or syringe-like insertion device, the implant may have
lateral stability thereby preventing or decreasing bending or
buckling of the implant while it is being pushed into the surgical
site (e.g., the cavity or hole).
[0162] In some embodiments of the present invention, entanglement
of the DBF may be increased by stirring the fibers while in a
liquid slurry. By creating a vortex, fibers are swirled and induced
to become entangled. This entanglement results in non-woven `ropes`
of fibers that may be extruded and then cut to length and used as
is, or further processed into pellets as described in this
disclosure.
[0163] For the implants to swell post-implantation so that they are
substantially space-filling, control of the processing conditions
of the fibers may be controlled. For example, in some embodiments,
the fibers are compressed, heated, and/or otherwise dried in order
to render the fibers in a compact state such that upon wetting, the
fibers are able to expand and swell.
[0164] In some embodiments of the present invention, an implant
system package or implant kit includes the cylindrical molds and
plunger as shown, for example, in FIG. 4.
Excipients and Additives.
[0165] Additives are contemplated to modify biological or other
properties of the implant according to embodiments of the present
invention. Non-limiting examples of additives include growth
factors such as bone morphogenetic proteins (BMPs), including
BMP-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9,
BMP-10, BMP-11, BMP-12, BMP-13, BMP-15, BMP-16, BMP-17, and BMP-18;
Vascular Endothelial Growth Factors (VEGFs), including VEGF-A,
VEGF-B, VEGF-C, VEGF-D and VEGF-E; Connective Tissue Growth Factors
(CTGFs), including CTGF-1, CTGF-2, and CTGF-3; Osteoprotegerin,
Transforming Growth Factor betas (TGF-.beta.as), including
TGF-.beta.-1, TGF-.beta.-2, and TGF-.beta.3, and inhibitors for
tumor necrosis factor (e.g., anti-TNF-.alpha.). Morphogens may also
include Platelet Derived Growth Factors (PDGFs), including PDGF-A,
PDGF-B, PDGF-C, PDGF-D, and GDF-5; rhGDF-5; and LIM mineralization
protein, insulin-related growth factor-I (IGF-I), insulin-related
growth factor-II (IGF-II), fibroblast growth factor (FGF) and
beta-2-microglobulin (BDGF II), as disclosed in the U.S. Pat. No.
6,630,153, the entire contents of which is incorporated herein by
reference. The polynucleotides encoding the same may also be
administered as gene therapy agents. The preferred bioactive
substances are the recombinant human bone morphogenetic proteins
(rhBMPs) because they are available in relatively unlimited supply
and do not transmit infectious diseases. In some embodiments, the
bone morphogenetic protein is a rhBMP-2, rhBMP-4, rhBMP-7, or
heterodimers thereof. BMPs are available from Wyeth, Madison, N.J.,
and may also be prepared by one skilled in the art as described in
U.S. Pat. No. 5,366,875 to Wozney et al.; U.S. Pat. No. 4,877,864
to Wang et al.; U.S. Pat. No. 5,108,922 to Wang et al.; U.S. Pat.
No. 5,116,738 to Wang et al.; U.S. Pat. No. 5,013,649 to Wang et
al.; U.S. Pat. No. 5,106,748 to Wozney et al.; and PCT Patent Nos.
WO93/00432 to Wozney et al.; WO94/26893 to Celeste et al.; and
WO94/26892 to Celeste et al., the entire contents of all of which
are herein incorporated by reference.
[0166] Oxygenating additives such as perfluorocarbons may be used
to further enhance the bone formation and healing of the DBF
material in the implant of the present disclosure. In some
embodiments, the bone repair DBF implant composition includes
oxygenating materials such as a perfluorocarbon (PFC). In some
embodiments, the DBF implant composition includes oxygen generating
compounds such as peroxides (e.g., hydrogen peroxide, magnesium
peroxide, calcium peroxide), perchlorates (e.g., sodium
perchlorate, potassium perchlorate), percarbonates (e.g., sodium
percarbonate), or perborates (e.g., sodium perborate).
[0167] For additional benefits, cancellous or cortical bone chips
and/or demineralized cancellous or cortical bone chips may be added
to the DBF. In addition to or alternatively to the bone chips,
mineralized bone fibers may be added to the DBF. In addition to
bone chips, mineralized bone fibers or alternatively, calcium
phosphate, tri-calcium phosphate, hydroxyapatite, or other
synthetic bone graft materials may be added to the DBF.
[0168] According to some embodiments of the present invention,
introduction of an implant for screw augmentation into a patient is
accomplished by placing the implant into a hole that has been
drilled to receive a screw. The implant is sized to fit the hole to
be repaired and to be space filling, i.e., the implant is of
approximately the same length and diameter as the hole. The implant
may be placed in the hole directly by hand or may be placed by use
of a delivery instrument having a cylindrical element to hold the
implant with a plunger to expel it. Accordingly, the delivery
instruments may be cannulated.
[0169] In some embodiments of the present invention, the implant is
longer than the depth of the hole to be treated and in these
instances the surgeon may cut the implant to a desired length.
[0170] Forming an indentation into the end of the implant designed
to receive the screw may facilitate central placement of the screw.
Additionally, the implant may be cannulated or tubular to further
facilitate screw placement over a guide wire.
[0171] In some embodiments of the present invention, implants are
formed and stored in tubes. To facilitate loading into the end of
the delivery tube a recess is formed in the end of the elongated
member (e.g., cannula) to hold the storage tube in correct
alignment.
[0172] In some embodiments a plurality of implants are stored in a
holder that is configured to attach to a delivery tube to allow
easy deployment of implants.
[0173] The delivery tube may be straight or curved. In the latter
instance the plunger will be flexible, being made of any suitable
material, for example, nitinol wire or braided nitinol wire.
[0174] The DBF implant may be shaped with a convex proximal end and
concave distal end by the push rod. Alternatively, implants may be
introduced by separate means into the end of the delivery tube. In
some instances, implants having a pellet shape may be easier to
introduce into delivery tubes.
[0175] At the time of surgery, prior to implantation, a small
amount of any suitable water-soluble contrast agent may be injected
into the implant to provide visualization during implantation. An
example of a water-soluble contrast agent is Iopamidol.
[0176] At the time of surgery and prior to implantation, a small
amount of sterile water, phosphate buffered saline, bone marrow
aspirate, and/or blood may be injected into the implant to hydrate
the implant.
EXAMPLES
[0177] The following examples use cortical human bone. As discussed
herein, either human or animal bone may be used as a source of
cortical bone. Fibers were produced using the methodology as
described in U.S. Pat. Nos. 9,486,557 and 9,572,912, supra.
Example 1
[0178] 1 ml disposable plastic syringes were used as a mold. The
plungers were removed and 0.25 grams of DBF were introduced into
the end of the syringe and the plunger used to lightly compress the
fibers to a length of approximately 4 cm. The plungers were removed
and the tip of the syringe cut off using a scalpel. The implants
were vacuum dried overnight at 27.degree. C. The resultant implants
were approximately 4.5 mm in diameter
Example 2
[0179] Three implants from Example 1 were used to test for
augmentation of screw pull out. A Sawbones 10 pores per inch foam
that is frequently used to test screw pull out as a surrogate for
osteopenic bone was used. Six 5 mm diameter holes were drilled in
the foam block. Implants from example 1 were placed in three of the
holes. 5.5 mm pedicle screws were inserted into the six holes. An
MTS tensile test machine was used to record the force required to
pull the screws out of the holes. The data obtained are shown in
Table 1 below.
TABLE-US-00001 TABLE 1 Peak Force (N) Control Augmented Test 1 346
764 Test 2 338 868 Test 3 290 778 Average 325 803
Example 3
[0180] 15 grams of DBF fiber were wet laid in a 10 cm.times.11 cm
flat mold to produce a sheet of DBF. The mold was heated at
55.degree. C. for two hours to bond the fibers and dry the sheet.
The sheet was approximately 1 mm thick. A portion of the sheet
would be suitable for use in augmenting ACL or rotator cuff
fixation.
Example 4
[0181] A portion of the sheet of Example 3 was cut to the shape of
the tibial tray from a knee arthroplasty, hydrated and pressed onto
the surface of the porous coated tibial tray.
Example 5
[0182] A portion of the sheet of Example 3 approximately 3 cm by 1
cm was hydrated and wrapped around the threaded portion of a 6 mm
diameter pedicle screw. The DBF conformed to the surface of the
screw.
Example 6
[0183] An apparatus to make implants using a water assisted
injection molding (WAIM) was fabricated according to the schematic
shown in FIG. 16. A 20 ml syringe with its distal end removed was
placed in a 3D printed adapter. Three detachable mold sizes were
used, each 5 cm long with diameters of: 3.5 mm decreasing to 3 mm;
4.5 mm decreasing to 4 mm; and 5.5 mm decreasing to 4.5 mm. DBF was
placed in the 20 ml syringe and the syringe filled with PBS. The
end of the syringe was placed in the adapter and the plunger
pressed down to inject the DBF into the mold. DBF quantities used
were 0.45 gram, 0.6 gram and 1.05 gram for the 3.5, 4.5 and 5.5 mm
diameters respectively. After molding the molds were placed in a
vacuum oven and dried under vacuum with a 0.5 L/min air flow
overnight. After removal of the end caps the dried implants could
be simply removed by pushing from the molds. The implant diameters
were approximately 0.75 mm less in diameter than the mold
diameter.
Example 7
[0184] A portion of the sheet from Example 3 was cut into two
pieces each 2 cm.times.5 cm with a slot cut in it as shown in FIG.
25a. The sheets were then rehydrated and using four 3 mm diameter
rods the cruciate form of FIG. 27a was formed. After drying the
implant is shown in FIG. 27b. This implant was suitable for use in
augmenting the fixation of an ad graft.
Example 8
[0185] A portion of the sheet from Example 3 was cut into one piece
approximately 2 cm.times.5 cm. The sheet was then rehydrated and
shaped using two 3 mm diameter rods and then redried. The implant
of FIG. 27c was formed. This implant was suitable for use in
augmenting the fixation of a two strand ad graft.
[0186] While the present invention has been illustrated and
described with reference to certain exemplary embodiments, those of
ordinary skill in the art will understand that various
modifications and changes may be made to the described embodiments
without departing from the spirit and scope of the present
invention, as defined in the following claims.
[0187] Additionally, although relative terms such as "outer,"
"inner," "upper," "lower," "below," "above," "vertical,
"horizontal" and similar terms have been used herein to describe a
spatial relationship of one element to another, it is understood
that these terms are intended to encompass different orientations
of the various elements and components of the device in addition to
the orientation depicted in the figures (Figs.).
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