U.S. patent number RE46,261 [Application Number 14/458,322] was granted by the patent office on 2017-01-03 for instruments for expandable corpectomy spinal fusion cage.
This patent grant is currently assigned to DePuy Synthes Products, Inc.. The grantee listed for this patent is DePuy Synthes Products, LLC. Invention is credited to Martin Meer, Gerhard Pohl, Glen Arthur Presbrey, Katherine Herard Ray, Robert E. Sommerich.
United States Patent |
RE46,261 |
Sommerich , et al. |
January 3, 2017 |
Instruments for expandable corpectomy spinal fusion cage
Abstract
An instrument set for an intervertebral expandable spacer having
a pair of co-axial annuluses locked together by an engagement
member, the set including an inserter/expander having both a rapid
expansion mechanism and a fine tuning expansion mechanism.
Inventors: |
Sommerich; Robert E. (Norton,
MA), Presbrey; Glen Arthur (Mapleville, RI), Meer;
Martin (Vohringen, DE), Pohl; Gerhard (St.
Georgen, DE), Ray; Katherine Herard (Reston, VA) |
Applicant: |
Name |
City |
State |
Country |
Type |
DePuy Synthes Products, LLC |
Raynham |
MA |
US |
|
|
Assignee: |
DePuy Synthes Products, Inc.
(Raynham, MA)
|
Family
ID: |
40789558 |
Appl.
No.: |
14/458,322 |
Filed: |
August 13, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
|
11960623 |
Aug 14, 2012 |
8241363 |
|
|
Reissue of: |
12055805 |
Mar 26, 2008 |
8241294 |
Aug 14, 2012 |
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F
2/4611 (20130101); A61F 2/44 (20130101); A61F
2/4611 (20130101); A61F 2/44 (20130101); A61F
2002/30367 (20130101); A61F 2002/4622 (20130101); A61F
2002/4628 (20130101); A61F 2002/4628 (20130101); A61F
2002/4622 (20130101); A61F 2220/0025 (20130101); A61F
2002/2835 (20130101); A61F 2002/30367 (20130101); A61F
2002/30841 (20130101); A61B 2017/0256 (20130101); A61F
2002/30601 (20130101); A61F 2220/0033 (20130101); A61F
2002/30507 (20130101); A61F 2002/30784 (20130101); A61F
2002/3055 (20130101); A61F 2002/449 (20130101); A61F
2002/30784 (20130101); A61F 2002/30507 (20130101); A61F
2002/3055 (20130101); A61B 2017/0256 (20130101); A61F
2002/449 (20130101); A61F 2002/2835 (20130101); A61F
2220/0033 (20130101); A61F 2002/30601 (20130101); A61F
2002/30841 (20130101); A61F 2220/0025 (20130101); A61F
2002/30593 (20130101) |
Current International
Class: |
A61B
17/58 (20060101); A61F 2/46 (20060101); A61F
2/44 (20060101); A61F 2/28 (20060101); A61F
2/30 (20060101); A61B 17/02 (20060101) |
Field of
Search: |
;606/90,99,105,205,210
;81/302,355,352-354 ;269/256,211 ;600/222 ;623/17.11 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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968692 |
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Jan 2000 |
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EP |
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1090703 |
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Apr 2001 |
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EP |
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1188424 |
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Mar 2002 |
|
EP |
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1491165 |
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Dec 2004 |
|
EP |
|
9963913 |
|
Dec 1999 |
|
WO |
|
WO 02071986 |
|
Sep 2002 |
|
WO |
|
Other References
Russegger, "First Experiences With A Distractible Titanium Implant
In Vvntral Cervical Disc Surgery: Report On 30 Consecutive Cases",
Eur Spine J, 1997; 6(1), pp. 70-73. cited by applicant .
Coumans, "Use of the Telescopic Plate Spacer in Treatment of
Cervical and Cervicothoracic Spine Tumors", Neurosurgery, Aug. 2005
vol. 51(2), pp. 417-426. cited by applicant .
Pederson, "Thermal Assembly of a Biometric Mineral/Collagen
Composite", Biomaterials. Nov. 2003; vol. 24(26), pp. 4881-4890.
cited by applicant .
Pflugmacher, "Biomechanical Comparison of Expandable Cages for
Vertebral Body Replacement in the Thoracolumbar Spine", SPINE, Jul.
1, 2004, vol. 29(13), pp. 1413-1419. cited by applicant .
Woiciechowsky, "Distractable Vertebral Cages for Reconstruction
After Cervical Corpectomy", SPINE, Aug. 1, 2005, vol. 30(15), pp.
1736-1741. cited by applicant .
Kandziora, "Biomechanical Comparison of Expandable Cages for
Vertebral Body Replacement in the Cervical Spine", J Neurosurg,
Jul. 2003, vol. 99(1), pp. 91-97. cited by applicant .
Thongtrangan, "Vertebral Body Replacement With an Expandable Cage
for Reconstruction After Spinal Tumor Resection", Neurosurg Focus,
Nov. 15, 2003, vol. 15(5) p. E8. cited by applicant .
Krbec, "Replacement of the Vertebral Body With an Expansion
Implant", Acta Chir Orthop Traumataol Cech , 2002, pp. 158-162,
vol. 69(3)--Abstract Only. cited by applicant .
Kazan, "Percutaneous Anterior Odontoid Screw Fixation Tetchnique. A
New Instrument and a Cadveric Study", Acta Neurochir Wien, 1999,
pp. 521-524, vol. 141(5)--Abstract Only. cited by applicant .
Khodadadyan-Klostermann, "Expandable Cages: Biomechanical
Comparison of Different Cages for Ventral Spondylodesis in the
Thoracolumbar Spine", Chirug, Jul. 2004, pp. 694-701, vol.
75(7)--Abstract Only. cited by applicant.
|
Primary Examiner: Wehner; Cary
Attorney, Agent or Firm: Nutter McClennen & Fish LLP
Parent Case Text
CONTINUING DATA
This continuation-in-part patent application claims priority from
co-pending U.S. Ser. No. 11/960,623, filed Dec. 19, 2007, entitled
"Expandable Corpectomy Spinal Fusion Cage" (Sommerich)
(DEP6073USNP)
Claims
We claim:
1. An inserter/expander instrument comprising: a) a first
longitudinal member having a distal end portion .[.adapted for
engaging a first vertebral surface.]., an intermediate portion, and
a proximal portion, b) a second longitudinal member having a distal
end portion .[.adapted for engaging a second vertebral surface.].,
.Iadd.and .Iaddend.an intermediate portion, .[.and a proximal
portion,.]. c) first and second cross bars distally pivotally
attached to the longitudinal members at distal pivots; pivotally
attached together at a third pivot; and slidably attached at their
respective proximal ends to the opposing longitudinal member by a
pin and groove arrangement, d) a first expansion actuation
mechanism attached to the proximal portion of the first
longitudinal member, the expansion actuation mechanism adapted to
incrementally distally advance the proximal portion .Iadd.of the
.Iaddend.first cross bar to expand the distal portions of the
longitudinal members, and e) a second expansion actuation mechanism
attached to the proximal portion of the first longitudinal member,
the second expansion actuation mechanism adapted to incrementally
distally advance the proximal portion of the first cross bar to
expand the distal portions of the longitudinal members, wherein the
second expansion mechanism comprises a knob having a threaded shaft
extending therefrom, the thread of the shaft mating with a thread
.[.upon.]. .Iadd.on .Iaddend.an internal diameter of a tube located
.[.with.]. .Iadd.within .Iaddend.the first longitudinal member, and
wherein the shaft of the knob is connected to the pin of the pin
and groove arrangement, so that distal movement of the shaft of the
knob results in an opening of the cross bars.
2. The instrument of claim 1 wherein the first expansion mechanism
comprises a pistol grip comprising a handle and lever pivotally
attached to the handle.
3. The instrument of claim 2 wherein the lever is pivotally
attached to a shaft located within the proximal portion of the
first longitudinal member.
4. The instrument of claim 1 wherein the proximal portion of the
first longitudinal member is cannulated.
.Iadd.5. The instrument of claim 1, wherein the first longitudinal
member distal end portion is adapted for engaging a first vertebral
surface and the second longitudinal member distal end portion is
adapted for engaging a second vertebral surface..Iaddend.
.Iadd.6. The instrument of claim 1, wherein the first longitudinal
member distal end portion and the second longitudinal member distal
end portion are each modular..Iaddend.
.Iadd.7. The instrument of claim 6, wherein the first longitudinal
member modular distal end portion is adapted for engaging a first
vertebral surface and the second longitudinal member modular distal
end portion is adapted for engaging a second vertebral
surface..Iaddend.
.Iadd.8. The instrument of claim 6, wherein the first longitudinal
member modular distal end portion and the second longitudinal
member modular distal end portion are each adapted for holding an
expandable implant..Iaddend.
.Iadd.9. The instrument of claim 1, wherein the first longitudinal
member distal end portion and the second longitudinal member distal
end portion are each adapted for holding an expandable
implant..Iaddend.
Description
BACKGROUND OF THE INVENTION
One conventional spinal implant used in corpectomy cases is an
intervertebral spacer for insertion between two vertebrae, wherein
the spacer has an adjustable axial height, an annular first member
and a second member which is guided within the first member and
displaceable in axial direction relative to the first member for
adjustment of the overall height.
Conventional spacers of this type of are often expanded by a
threaded connection between the outer surface of the inner member
and the inner surface of the outer member. The opposite ends of the
spacer are often provided with spikes for secure seating into the
adjacent vertebra. However, the requirement of rotating the members
around the longitudinal axis also rotates the spikes, thereby
risking injury to the adjacent vertebrae.
U.S. Pat. No. 6,200,348 (Biedermann) discloses a spacer that is
expandable without the need for rotation. The locking mechanism of
the U.S. Pat. No. 6,200,348 includes a i) a pair of set screws,
each set screw having a hemispherical distal end that seats in an
outer annulus, and ii) a row of mating hemispherical recesses
extending into an inner annulus.
SUMMARY OF THE INVENTION
The present inventors have appreciated that although the spacer
design disclosed in U.S. Pat. No. 6,200,348 has advantageously
eliminated the need to rotate the pair of sleeved cage components
in order to expand its height, it nonetheless does not contain a
graft window. A graft window is a large opening in the face of the
cage--an opening much larger than the diamond shaped holes provided
in U.S. Pat. No. 6,200,348--used to insert graft into the cage.
Providing a graft window is helpful in that it provides the surgeon
with an access port into the center space of the cage through which
the surgeon may insert bone graft into the cage. When a graft
window is not provided, bone graft must be inserted into the cage
prior to insertion of the cage into the spine (i.e., when the cage
is in its unexpanded configuration). Thus, when the cage is later
inserted into the spine and then expanded, the newly expanded
portion of the cage contains no graft. Providing a graft window is
helpful in that it allows the surgeon to place the cage into the
spine, expand the cage and then fill the expanded cage with bone
graft. Accordingly, there is no unfilled space in the expanded
inserted cage having a graft window.
Therefore, in accordance with the present invention, there is
provided a spacer for insertion between two vertebrae, the spacer
having a variable axial height and comprising a first member and a
second member guided within the first member to be slidable
relative thereto in an axial direction thereof for adjusting an
overall height,
wherein the second member comprises an outer wall and ratchet
notches provided at its outer wall facing the first member and
extending in the axial direction,
wherein the first member comprises a wall having an engagement
member, which cooperates with the ratchet notches for adjusting the
overall height of the spacer, and
wherein the first member has a graft window therein for inserting
graft material therethrough.
However, when the present inventors set out to modify the cage of
U.S. Pat. No. 6,200,348 with a graft window, they found that
inclusion of the graft window would either require removal of the
locking mechanism to another location (such as the distal portion
of the inner annulus, as shown in FIG. 6 below) or require that the
graft window be very small.
The present inventors thus set out to redesign the locking
mechanism of U.S. Pat. No. 6,200,348 so that inclusion of a graft
window would not require removal of the locking mechanism to
another location, nor require that the graft window be very
small.
The present inventors found that replacing the set screw/spherical
recess locking mechanism of U.S. Pat. No. 6,200,348 with a new
mechanism solved the above noted problem. The new mechanism is an
engagement member which comprises i) a set screw and ii) a pressure
plate having an outer face contacting the set screw and an inner
face having teeth adapted to mate with the ratchet notches of the
second member
Moreover, the present inventors found that the new locking
mechanism imparted a superior strength to the cage so that only one
set screw was needed to lock the cage in its expanded
condition.
Also in accordance with the present invention, there is provided a
spacer for insertion between two vertebrae, said spacer having a
variable axial height and comprising a first member and a second
member guided within the first member to be slidable relative
thereto in an axial direction thereof for adjusting an overall
height,
wherein the second member comprises an outer wall and ratchet
notches provided at its outer wall facing the first member and
extending in the axial direction,
wherein the first member comprises a wall having an engagement
member, which cooperates with the ratchet notches for adjusting the
overall height of the spacer, and
wherein the engagement member comprises i) a set screw and ii) a
pressure plate having an outer face contacting the set screw and an
inner face having teeth adapted to mate with the ratchet notches of
the second member.
DESCRIPTION OF THE FIGURES
FIGS. 1a and 1b disclose front and back views of a cage of the
present invention.
FIG. 1c discloses a cage of the present invention having windows in
both annuluses.
FIG. 2a discloses a cage of the present invention in which the
teeth of the pressure plate mate with the notches on the inner
annulus.
FIG. 2b discloses details of the engagement mechanism of the
present invention.
FIG. 3a discloses a perspective view of the engagement member of
the present invention.
FIG. 3b discloses a cross-section of the engagement mechanism of
the present invention having a pressure plate.
FIGS. 4a-4c disclose cages of the present invention respectively
adapted for lateral, direct anterior and postero-lateral
insertion.
FIG. 5 discloses a cage having the graft window on its inner
annulus.
FIG. 6 discloses a cage of the present invention wherein the
engagement mechanism comprises a pressure plate located on the
distal portion of the inner second annulus and the notches located
on the inner portion of the outer first annulus.
FIG. 7 discloses an inserter-expander instrument for inserting and
expanding the cage of the present invention.
FIG. 8a discloses an inserter/expander instrument provided with a
pistol grip
FIG. 8b discloses a second view of the inserter/expander instrument
provided with a pistol grip
FIGS. 9a-9c disclose the pistol grip portion of the instrument
rotated to three positions.
FIG. 9d discloses a closeup of the guide and safety components on
the distal tips.
FIG. 9e discloses a closeup of the safety flange component of the
inserter-expander.
FIG. 9f discloses a closeup of the location of the spring component
of the inserter-expander.
FIG. 9g discloses a closeup of the modular arms and associated push
button components of the inserter-expander.
FIG. 9h discloses a closeup of the dual ratchet mechanism with
offset components of the inserter-expander.
FIGS. 10a-10f disclose an embodiment of the second distractor and
various portions thereof.
FIG. 11 discloses a plurality of endplate trials used with a
posterior approach cage.
FIG. 12 discloses a graft loading block.
FIG. 13 discloses a bone tamp.
FIG. 14 discloses a grabber anti-torque instrument.
FIG. 15 discloses a pair of positioning impactors.
DETAILED DESCRIPTION OF THE INVENTION
For the purposes of the present invention "spacer" and "cage" are
used interchangeably.
Now referring to FIG. 1 there is provided a spacer for insertion
between two vertebrae, the spacer having a variable axial height
and comprising a sleeve-shaped first member 1 and a second member 2
guided within the first member to be slidable relative thereto in
an axial direction thereof for adjusting an overall height,
wherein the second member comprises an outer wall 3 and ratchet
notches 5 provided at its outer wall facing the first member and
extending in the axial direction, and
wherein the first member comprises a wall 7 having an engagement
member 9, which cooperates with the ratchet notches for adjusting
the overall height of the spacer,
wherein the first member has a window 10 therein for inserting
graft material therethrough, and
wherein the engagement member 9 comprises i) a set screw 11 and ii)
a pressure plate 13 having an outer face 15 contacting the set
screw and an inner face 17 having teeth 19 adapted to mate with the
ratchet notches of the second member.
The first member generally has a tubular shape comprising a first
annulus 21. The outer end of the first member should be adapted to
seat upon a lower vertebral endplate, and so a substantially flat
endplate 25 is generally attached to the outer end 27 of the first
annulus. This endplate generally has a hole in its center and
extends outwardly substantially radially from the outer end of the
annulus. The outer face 28 of the endplate should be adapted to
grip the lower vertebral endplate and so is generally provided with
roughened features 29. These roughened features may be a plurality
of uniformly distributed, pointed teeth 31 that bite into the
adjacent endplate. In other embodiments, the teeth may be
non-uniformly distributed. For further insuring that the endplate
will be stably seated into the vertebral endplate, the outer face
of the endplate may also have a few long spikes 33 extending
therefrom. In some embodiments, the endplate has an overall convex
shape in order to suitably conform to the overall concave shape of
the natural vertebral endplate in which it seats. In some
embodiments (as in FIG. 1c), the endplate has a wedge cross-section
in order to conform to the lordosis adopted by the natural spine in
the region of the implant. Typically, the wedge is designed to
provided a lordotic angle of between about 0 and about 24 degrees,
more typically between about 6 and about 12 degrees. The wedge may
also be designed to provided a kyphotic angle of between about 0
and about -12 degrees,
In general, the outer dimensions of the endplates of the present
invention are between about 16 mm and about 30 mm (e.g.,
16.times.20; 20.times.23 and 24.times.30).
The annular portion of the first member also comprises a plurality
of uniformly distributed, transverse, through-holes 35. These
throughholes are generally about 2-8 mm in diameter, and provide a
means for bone growth therethrough. The holes are preferably of
diamond shape, although other shapes such as triangles may be used.
When in a diamond shape, suitable sizes include 2.5 mm.times.3.5 mm
shapes to 5 mm.times.7 mm shapes. In the particular FIGS. 1a and
1b, the throughholes have a diamond shape. The diamond shape allows
the annulus material to make a mesh pattern in the wall that has
structural advantages. However, any conventional shape may be used
for the through-hole pattern. In some embodiments, the plurality of
throughholes occupy only the distal portion 37 of the annulus. In
such an embodiment, graft windows may be placed both on the
proximal 39 and lateral 41 portions of the annulus. This has the
advantage of allowing the surgeon to place bone graft into the cage
from a variety of angles. In some embodiments, the plurality of
throughholes occupy not only the distal portion of the first
annulus, but also the lateral portions as well. In such an
embodiment, graft windows may be placed only through the proximal
portion of the annulus, but the cage has the structural advantage
of extra strength.
The first member generally has at least one graft window 10
therein. The graft window functions both as a path through which
the surgeon can place bone graft into the cage, but also as a means
for bone growth therethrough. In other embodiments, the first
member has a plurality of graft windows therein. When a face of the
annulus has been selected for graft windows, in preferred
embodiments, two graft windows 43 are placed one on top of the
other, being separated by a bar 45. This bar enhances the strength
of the cage. In the particular cage shown in FIG. 1a, there are two
graft windows on the proximal face of the annulus, two graft
windows on the left lateral face of the annulus and two graft
windows on the right lateral face of the annulus. This
configuration represents a balance between providing surgeon
flexibility (through the inclusion of multiple faces with graft
windows) and cage strength (through the use of a lateral bar
between windows on any face). Each window typically has a diameter
of between about 5 mm and about 20 mm. Typical windows measure 5.5
mm.times.5.6 mm to 12 mm.times.15.75 mm to 17.5 mm.times.12 mm.
The first member may preferably include a reinforcing collar 47
surrounding the inner (upper) end portion 48 of the first annulus.
The function of the reinforcing collar is to strengthen the first
member and reduce deflection when the screw is tightened. The
reinforcing collar also generally has a threaded screw hole
extending radially therethrough. This threaded screw hole is
adapted for threadable passage of a threaded locking set screw
therethrough.
Now referring to FIG. 2a, the first member comprises a collar 47
having an engagement member 9 therein, and the engagement member
cooperates with the ratchet notches of the second member for
adjusting a desired overall height of the spacer.
Now referring to FIG. 2b, there is provided a more detailed
understanding of the engagement member. The engagement member 9
comprises i) a set screw 11 and ii) a pressure plate 13 having an
outer face 15 contacting the set screw and an inner face 17 having
teeth 19 adapted to mate with the ratchet notches of the second
member.
In some embodiments, as in FIG. 2b, a cylindrical outer surface 20
of the set screw is threaded to allow its advance toward the second
member. In some embodiments, as in FIGS. 3a and 3b, the set screw
is tubular with internal axial recesses 22 therein extending along
its axis. These axial recesses mate with a screwdriver, thus
allowing the screw to be rotated and thereby advanced towards the
second member.
The set screw further has a neck and head extension 49 extending
from its distal end 50, wherein the extension is shaped so as to
both provide engagement with a corresponding recess 51 of the
pressure plate and allow its rotation during that engagement.
Now referring to FIGS. 3a and 3b, the pressure plate 13 has an
outer face 15 contacting the set screw and an inner face 17 having
teeth 19 adapted to mate with the ratchet notches of the second
member. The outer face has a neck and head recess 51 therein that
corresponds with the head and neck extension of the set screw so as
to both provide engagement with a corresponding extension of the
set screw and allow rotation of the set screw during that
engagement. The pressure plate is seated on the inside face of the
collar.
The inner face of the pressure plate has at least two elongated
teeth 19 thereon forming at least one notch therebetween. The tips
of the teeth are preferably spaced apart a distance of between
about 1 mm and 2 mm, generally about 1.5 mm. The spacing can be
larger or smaller than these values, with smaller being
preferable.
Now referring to FIG. 1b, the distal 37 portion of the first member
also has an assembly pin 53 extending radially inward from the
collar. This assembly pin slidably mates with a corresponding
assembly groove 54 of the second member in order to maintain the
second member in a slidable orientation within the first member,
and to retain the first member to the second member.
Still referring to FIG. 1b, the second member generally has a
tubular shape comprising a second annulus 55. The outer diameter of
the second annulus should be slightly smaller than the inner
diameter of the first annulus of the first member, in order to
provide slidable reception of the second annulus within the first
member.
The outer end of the second member should be adapted to seat upon
an upper vertebral endplate, and so a substantially flat endplate
57 is generally attached to the outer end 59 of the second annulus
55. This endplate generally has a hole in its center and extends
outward substantially radially from the upper end of the annulus.
The outer face of the endplate should be adapted to grip the upper
vertebral endplate and so is generally provided with roughened
features 29. These roughened features may be a plurality of
uniformly (or non-uniformly) distributed, pointed teeth 31 that
bite into the adjacent endplate. For further insuring that the
endplate will be stably seated into the vertebral endplate, the
outer face of the endplate may also have a few long spikes 33
extending therefrom. In some embodiments, the endplate has an
overall convex shape in order to suitably conform to the overall
concave shape of the natural vertebral endplate in which it
seats.
The annular portion of the second member also comprises a plurality
of uniformly distributed, transverse, through-holes 35. These
throughholes are generally of the throughhole size discussed above,
and provide a means for bone growth therethrough. In this
particular FIG. 1a, the throughholes have a diamond shape. The
diamond shape allows the second annulus material to make a mesh
pattern that has structural advantages. However, any conventional
shape may be used for the through-hole pattern. In some
embodiments, the plurality of throughholes occupy each of the
lateral faces of the posterior portion of the second annulus.
The second member may preferably include a reinforcing collar 61
surrounding the outer (upper) end portion 59 of the second annulus.
The function of this reinforcing collar is to allow for instrument
attachment. The reinforcing collar also generally has a plurality
of through-holes 63 extending radially therethrough. These
throughholes function as areas for instrument attachment, and as
areas for bone growth and vascularization.
The proximal portion 65 of the second annulus has a plurality of
elongated teeth 67 thereon forming at least one notch 69
therebetween. These teeth and notches form a row extending up the
outside of the annulus. Typically, the annulus of the second member
has at least ten elongated notches thereon. These notches are
formed to compliment the teeth of the pressure plate. The apices of
the notches on the second member are generally spaced apart a
distance of between about 1 mm and 2 mm, generally about 1.5 mm.
The spacing can be larger or smaller than these values, with
smaller being preferable.
The distal 70 portion of the second annulus of the second member
also has an assembly groove 54 extending inwardly and axially along
the outside 68 of the second annulus. This assembly groove mates
with the corresponding assembly pin of the first member in order to
maintain the second member in a slidable orientation within the
first member.
Once the overall height of the cage has been determined by the
surgeon and the relative disposition of the first and second
members set accordingly, the set screw is then rotated by the
surgeon using a screwdriver. The set screw acts to advance the
pressure plate so that the teeth on the pressure plate contact the
ratchet notches of the second member, thereby locking the desired
overall height of the cage.
The general design of the cage of the present invention provided in
FIGS. 1a and 1b may be altered in order to be suit the approach
used to implant the cage.
For example, now referring to FIG. 4a, there is provided a cage
suited for a lateral approach. A lateral approach is generally
characterized by a surgical opening on a lateral side of the spine.
Accordingly, the Lateral cage of FIG. 4a possesses a graft window
71 that opens onto a lateral side 73 of the outer annulus. This
allows the surgeon to conveniently place graft into the cage
through the lateral surgical opening used to approach the
spine.
For example, now referring to FIG. 4b, there is provided a cage
suited for a direct anterior approach. A direct anterior approach
is generally characterized by surgical opening on the anterior
portion of the spine. Accordingly, the Direct Anterior cage of FIG.
4b possesses a graft window 75 that opens onto a generally anterior
side 77 of the outer annulus. In some embodiments, the window is
oriented 45 degrees to the endplates in order to avoid the great
vessels. This allows the surgeon to conveniently place graft into
the cage through the anterior surgical opening used to approach the
spine.
For example, now referring to FIG. 4c, there is provided a cage
suited for a postero-lateral approach. A postero-lateral approach
is generally characterized by a surgical opening on a
postero-lateral side of the spine. Accordingly, the postero-lateral
cage of FIG. 4c possesses a graft window 79 that opens onto a
postero-lateral side 81 of the outer annulus. This allows the
surgeon to conveniently place graft into the cage through the
postero-lateral surgical opening used to approach the spine. The
window of this cage is placed so that it opens to the surgeon. In
some embodiments, the endplates of this cage are substantially
circular so as not to be approach-specific.
Typically, the cages of the present invention are designed to
occupy either one, two or three levels of a thoracolumbar
corpectomy. In some embodiments having either 16 mm or 20 mm
endplate dimensions, the height of the cage can be between 22 mm
and 72 mm. In some embodiments having 24 mm endplate dimensions,
the height of the cage can be between 22 mm and 110 mm. In general,
the cage is designed to expand its height in an increment of
between about 8.5 mm to about 25 mm. Cages can be designed to
overlap in height ranges with their adjacent sizes. For example a
first cage can range in height from 25 to 33 5 mm, while a second
cage can range in height from 28.5 mm to 38.5 mm in height.
When the cage of the present invention is generally short (i.e., an
overall height of less than about 40 mm), it is advantageous to
provide the sole graft window on the second (inner) annulus. Now
referring to FIG. 5, there is provided a spacer for insertion
between two vertebrae, the spacer having a variable axial height
and comprising a sleeve-shaped first outer member 83 and a second
inner member 84 guided within the first member to be slidable
relative thereto in an axial direction thereof for adjusting an
overall height,
wherein the second member comprises an outer wall and ratchet
notches provided at its outer wall facing the first member and
extending in the axial direction,
wherein the first member comprises a wall having an engagement
member, which cooperates with the ratchet notches for adjusting the
overall height of the spacer, and
wherein the second member 84 has a window 85 therein for inserting
graft material therethrough.
In cages of the present invention characterized as tall (greater
than 40 mm), one annulus has a flange. Now referring to FIG. 1c,
there is provided a cage of the present invention having features
substantially the same as that of FIGS. 1a and 1b, except that the
proximal portion of the inner second annulus has a distal flange 87
upon its inner end portion 88.
In some embodiments, the features of the engagement mechanism are
reversed so that the pressure plate is located on the distal
portion of the inner second annulus and the notches are located on
the inner portion of the outer first annulus.
Now referring to FIG. 6, there is provided a spacer 101 for
insertion between two vertebrae, the spacer having a variable axial
height and comprising a sleeve-shaped first outer member 103 and a
second inner member 105 guided within the first member to be
slidable relative thereto in an axial direction thereof for
adjusting an overall height,
wherein the first outer member comprises an inner wall 107 and
ratchet notches 109 provided at its inner wall facing the second
member and extending in the axial direction, and
wherein the second inner member comprises a wall 111 having an
engagement member 113, which cooperates with the ratchet notches of
the first outer member for adjusting the overall height of the
spacer, and
wherein the engagement member comprises i) a set screw and ii) a
pressure plate having an outer face contacting the set screw and an
inner face having teeth adapted to mate with the ratchet notches of
the first outer member.
Instruments
In some embodiments, the instrument set used to implant the cage of
the present invention includes a) a pistol grip inserter/expander;
b) a secondary distractor; c) endplate trials (straight and
flexible); d) a bone graft loading block; e) bone tamps; f) a 3 Nm
torque limiting driver; g) a grabber/anti-torque instrument; and h)
positioning impactors.
(Inserter-Expander Instrument)
Conventional inserters for expandable cages are beset with a number
of challenges. First, if the cage is a threaded design, the
inserter does not allow for rapid expansion of the implant. Second,
conventional expanders do not provide significant tactile feedback
of the distraction of the vertebral bodies. Third, if the cage
requires rapid expansion, there is generally not an option for a
secondary method of expansion for expansion of smaller increments.
Fourth, there is no ability to rotate the handle to provide for
easier viewing into the spine.
Now referring to FIG. 7, there is provided an inserter-expander
instrument 115. This instrument is used to hold the cage during its
insertion and expand the cage after it has been inserted. This
instrument includes a modular inserter valve 117 for each size of
implant; threaded pins 119 adapted for alignment of the cage and a
third threaded rod (not shown) for attachment to the cage; a knob
121 for securing implant attachment to the inserter; a handle 123;
and a knob 125 for expanding and retracting the cage. Also shown is
a stand alone torque driver 124.
In use, the cage of the present invention is attached to the pins
119 by the surgeon using knob 121. Next, the cage is inserted into
the implant site. Knob 125 is then rotated to expand the implant to
the pre-determined height. Next, the cage height is locked by
advancing the set screw of the engagement member. Lastly, knob 121
is then rotated to release the pins from the implant.
Now referring to FIG. 8a, in some embodiments, the
inserter/expander instrument is provided with a pistol grip 127.
The pistol grip provides an advantage in that it provides rapid
implant expansion to contact the vertebral endplate.
Now referring to FIG. 8b, there is provided the inserter/expander
instrument of FIG. 8a now shown in an expanded position. The
inserter/expander instrument comprises: a) a first, upper
longitudinal member 501 having a distal end portion 503 adapted for
engaging a first vertebral surface, an intermediate portion 505,
and a proximal portion 507, b) a second, lower longitudinal member
511 having a distal end portion 513 adapted for engaging a second
vertebral surface, and an intermediate portion 515, c) first 517
and second 519 cross bars distally pivotally attached to the
longitudinal members at distal pivots 521; pivotally attached
together at a third pivot 523; and slidably attached at their
respective proximal ends to the opposing longitudinal member by a
pin and groove arrangement 525, d) a first expansion actuation
mechanism 527 attached to the proximal portion of the upper
longitudinal member, the expansion actuation mechanism adapted to
incrementally distally advance the proximal portion first cross bar
to expand the distal portions of the longitudinal members.
In the FIG. 8b, the expansion actuation mechanism 527 comprises a
pistol grip 529 having a handle 531 attached to the upper
longitudinal member, a pivotable lever 533 pivotally attached to
the handle, and pivotally attached to the upper longitudinal member
at a location 535 distal of the handle. The distal end 537 of the
lever is pivotally attached to a flange 539 extending from a shaft
541 slidably movable in the cannulated proximal portion 507 of the
upper longitudinal member. In use, gripping the lever results in a
distal movement of the shaft 541. Because the distal end of the
tube is connected to the pin of the pin and groove arrangement,
distal movement of the tube results in an opening of the cross
bars, and hence of opening of the distal end portions adapted for
engaging a first vertebral surface ("the distal tips").
In some embodiments (not shown), the first expansion actuation
mechanism can be a ratchet and pawl advancement mechanism, which
can comprise: i) a ratchet wheel having a centerpin pivotally
attached to the housing proximal to the grip, and a circumference
having a second plurality of teeth formed thereon shaped to engage
the first plurality of teeth, ii) a lever having a first end
portion pivotally attached to the ratchet wheel centerpin and a
second end portion having a shape adapted for gripping, and having
an outer surface having a pin extending therefrom, and iii) a pawl
having a first end pivotally attached to the pin of the lever and a
second end shaped for engaging the second plurality of teeth.
Any conventional means for incrementally expanding the distal tips
may be used as the first expansion actuation mechanism. Generally,
these are based upon advancing the shaft located within the
cannulated proximal portion of the upper longitudinal member. In
some embodiments, a ratchet and pawl mechanism is selected. In
others, the advancement mechanism comprises a rack and pinion
mechanism (such as a crank). In others, the advancement mechanism
comprises a friction-based mechanism and a leaf spring. In others,
the advancement mechanism comprises a tension band wound with a
pulley that is wound in.
Preferably, the inserter-expander also has a second expansion
actuation mechanism attached to the proximal portion of the first
longitudinal member and adapted for fine tuning the expansion of
the distal tips. Preferably, and now referring to FIG. 8b, this is
accomplished by provided a threaded knob 545 that is threadably
attached to the proximal end of the threaded tube housed within the
cannulated proximal portion of the upper longitudinal member.
Because the thread on the internal diameter of the tube and the
thread on the outer diameter of the shaft of the knob are mating
threads, turning the knob in a clockwise direction advances the
distal end of the shaft of the knob. Because the proximal end of
the shaft 549 of the knob is connected to the pin of the pin and
groove arrangement, distal movement of the shaft of the knob
results in an opening of the cross bars, and hence of opening of
the distal end portions adapted for engaging a first vertebral
surface ("the distal tips").
Thus, the fine tuning mechanism comprises: a second expansion
actuation mechanism attached to the proximal portion of the first
longitudinal member, the second expansion actuation mechanism
adapted to incrementally distally advance the proximal portion of
the second cross bar to expand the distal portions of the
longitudinal members. Preferably, the second expansion actuation
mechanism comprises a knob 545 having a threaded shaft 549
extending distally therefrom.
Now referring to FIG. 9a-9c, the pistol grip portion of the
instrument can be adapted to provide rotation. This pistol grip can
rotate and then lock into one of three positions. FIG. 9a shows the
pistol grip in the 0 degree position. FIG. 9b shows the pistol grip
in the 90 degree position. FIG. 9c shows the pistol grip in the 180
degree position. Now referring back to FIG. 8b, preferably, locking
of the rotatable pistol grip is accomplished by a locking sleeve
551.
Now referring to FIG. 9d, there are provided a guide and a safety
respectively located near the distal tips of the upper and lower
longitudinal members. The guide 553 is for reception of a
torque-limiting driver that can lock the expandable implant once
the desired height of the implant has been attained. The safety 555
prevents use of the torque driver if the implant has not been
expanded 5 mm. Accordingly, the safety prevents an unacceptably
short implant from being locked on top of the graft window.
Now referring to FIG. 9e, the inserter/expander also has another
safety flange 557 located on a proximal portion of the handle,
which protects the user from catching gloves or skin during the
ratchet lock release.
Now referring back to FIG. 8b, the inserter/expander also has a
push button 559, which when depressed, releases the ratchet
mechanism actuated by the pistol grip that holds the implant
extended. Now referring to FIG. 9f, the inserter/expander also has
a spring 560 located within the cannulated upper longitudinal
member that provides natural retraction of the pistol grip when the
push button is depressed.
Now referring back to FIG. 8b, the inserter/expander also has a
locking handle 561 extending through the lower longitudinal member
that threads the implant to the distal tips of the
inserter/expander. In this particular embodiment, the locking
handle comprises a knob 563 having a shaft 565 that extends to the
distal tips.
Now referring to FIG. 9g, the inserter/expander also has modular
arms 567. The detachability of these arms allows the surgeon to
accommodate different implant sizes and to easily detach the main
body of the inserter/expander from these arms, thereby allowing
x-rays to be easily taken. Push buttons .[.569.]. .Iadd.569a, 569b
.Iaddend.located on the inserter/expander main body allow the
surgeon to unlock these modular arms from the main body.
Now referring to FIG. 9h, the inserter/expander also has a dual
ratchet mechanism 571 with offset, which can provide smaller
incremental steps of expansion.
The current invention allows for a) a primary method of rapid
expansion using an ergonomic pistol grip design and b) a secondary
method of expansion for expanding a vertebral body replacement with
smaller height increments to optimize the patient fit. The pistol
grip design also provides tactile feedback to the physician as to
the distraction force placed on the spine as the implant expands.
In addition, the tips of the inserter/expander may be modular to
attach to different sized implants and also accommodate different
surgical approaches where different angles to the main body are
required.
Therefore, there are a number of advantages of the
inserter/expander of the present invention. First, it provides two
methods of expanding the implant within the same instrument.
Second, the instrument design provides for both for a) rapid, large
increment expansion and b) small, fine tuning increment expansion.
Third, the instrument has an ergonomic pistol grip. Fourth, the
instrument has a three-position pistol grip for maximum ergonomics.
Fourth, it has a guide for a set screw tightener. Fifth, it has
modular tips to accommodate different surgical approaches
(posterior, anterolateral, etc). Sixth, it has modular tips
designed to custom fit different implant sizes. Seventh, it has an
integrated safety feature to ensure that locking mechanism is not
allowed below a minimum distraction.
Now referring to FIGS. 10a-10c, there are provided figures of the
second distractor 131. The function of the second distractor is to
first distract the vertebral bodies located above and below the
implantation site to their normal anatomical position and then to
estimate the size of the implant required. FIG. 10a shows the
secondary distractor with lateral attachments 133 and a height
indicator 135. FIGS. 10b and 10c provide closeups of the distal end
of the secondary distractor having offset lateral attachments 137
(to estimate height for taller implants) and angled posterior
attachments 139 (for ease of use during posterior surgical
approaches).
FIG. 10b provides a closeup of the distal tip of a first preferred
secondary distractor having a laterally offset tip 137. This tip,
which preferably is provided in a modular form, can be suitably
used to estimate the intraspinous space for taller implants.
FIG. 10c provides a closeup of the distal tip of a second preferred
secondary distractor having a laterally offset tip 139 to be used
during posterior surgical approaches.
Now therefore, in accordance with the present invention, and now
referring to FIG. 10d, there is provided a distractor 251 for
distracting an intervertebral disc space, comprising: a) a first
longitudinal member 253 having a distal end portion 255 adapted for
engaging a first vertebral surface, an intermediate portion 351,
and a proximal handle portion 257, b) a second longitudinal member
263 having a distal end portion 265 adapted for engaging a second
vertebral surface, an intermediate portion 361, and a proximal
handle portion 267, the first and second longitudinal members being
pivotally attached at a pivot junction 271 between the proximal
handle and intermediate portions of each longitudinal member, c) a
height indicator 321 is also disposed at least partially between
handle portions of the longitudinal members and adapted to report a
height corresponding to a change in distance between the attachment
points of the proximal handle portions.
In some embodiments, the distal end portions of the distractor
comprises distal tips 281,283. The distal tips of the distractor
are adapted to enter the disc space and then distract the disc
space by moving apart. Accordingly, the combined thickness of the
distal tips should be as small as possible. The tips should be made
of material strong enough to withstand the resisting forces of the
supporting structures. The outer surfaces of the distal tips are
preferably sufficiently smooth to avoid damaging the opposing
vertebral walls.
In some embodiments, at least one of the distal end portions also
comprises a proximally-positioned .[.stops 285.]. .Iadd.stop, such
as stops 285a, 285b shown in FIG. 10D.Iaddend., which are designed
to abut the front wall of at least one of the opposing vertebral
bodies and prevent the surgeon from proceeding too far into the
disc space.
Preferably, these intermediate portions have a long length (e.g.,
at least 10 times the length of the corresponding distal tip)
sufficient to extend into the patient's body cavity, thereby
allowing its use in anterior approach procedures.
In some embodiments, the intermediate portion of the longitudinal
member consists essentially of a substantially rigid portion. This
has the advantage of manufacturing simplicity.
In other embodiments, as in FIG. 10e, the intermediate portion of
each member form a double action pivot 390 comprising second 391
and third 393 pivots, and a fourth pivot 395 distal to the double
action pivot, thereby defining proximal 401 and distal 405 portions
of the intermediate portion. In the embodiment of FIG. 10e, when
the proximal handle portions are squeezed together, first pivot 371
causes a distal widening of the proximal portions of the
intermediate portions, the double action pivot arrests the distal
widening between the distal portions of the intermediate portions,
and the fourth pivot causes a distal widening of the distal
portions of the device. Because the double action pivot arrests the
distal widening, it helps reduce the distance between the distal
tips when the proximal handles are squeezed together. Since large
distance changes between the proximal handles causes small distance
changes between the tips, this device provides both mechanical
advantage and sensitivity.
In the embodiment of FIG. 10f, there is provided first and second
cross bars 341, .[.143.]. .Iadd.343 .Iaddend.proximally pivotally
attached to the longitudinal members at the proximal pivots
291,293; pivotally attached together at a fourth pivot 295; and
slidably attached at their respective distal ends 345, 347 to the
opposing longitudinal member by a pin and groove arrangement. This
parallel action embodiment has the advantage of producing parallel
distal portions when the handles are squeezed together.
The junction of the proximal handle and intermediate portions of
each longitudinal member is adapted to accommodate a first pivot
for pivotally attaching the longitudinal members. Preferably, the
junction is located from the proximal handle end of the device a
distance of between about 10-50% of the overall length of the
device.
The first pivot is located at the junction between the intermediate
and proximal handle portions of the longitudinal members and is
adapted to effectively transmit force therebetween to open or close
the more distal portions longitudinal members without causing
deleterious jamming. In some embodiments, the first pivot is
adapted so that, when the proximal handles are squeezed together,
there is a narrowing of the longitudinal members. In other
embodiments, the first pivot is adapted so that, when the proximal
handles are squeezed together, there is a widening of the
longitudinal members.
Typically, the proximal handle portions of each longitudinal member
are adapted to produce a force to be transmitted distally when the
proximal handle portions are moved either towards each other (in
some instances) or away from each other (in some instances).
Preferably, these proximal handle portions have a long length
(e.g., at least 5 times the length of the corresponding distal tip)
sufficient to extend into the patient's body cavity, thereby
allowing its use in anterior approach procedures.
In some embodiments, the proximal handle portion consists
essentially of a substantially straight beam portion. This has the
advantage of simplicity in manufacturing.
In preferred embodiments, the proximal portion of the handle
portion has a surface 313 compatible for gripping by the surgeon.
In some embodiments, these gripping surfaces are disposed on the
outer facing surfaces 315 of the proximal portions of the handle
portions.
In some embodiments of the present invention, a height indicator
321 is also disposed at least partially between handle portions of
the longitudinal members. It typically comprises a graduated beam
323 pivotally attached to a proximal portion 325 of a first handle
portion and positioned to slide through a through hole 327
positioned on a proximal portion of a second handle portion. Prior
experimentation has determined the relationship between the
displacement of the two connection points (of the height indicator)
and the displacement between the two distal tips (which produce
distraction). Thus, when the device is used and the distance
between the connection points changes, the height indicator can
report the corresponding distance between the distal tips by
providing that corresponding distance on the graduated beam
adjacent the through hole. Typically, the height indicator also has
a stop 329 disposed at its unconnected end.
Typically, the components of the present invention can be made out
of any material commonly used in medical instruments. If the device
is designed to be reusable, then it is preferred that all the
components be made of stainless steel. If the device is designed to
be disposable, then it is preferred that some of the components be
made of plastic. Preferably, at least one component is sterilized.
More preferably, each component is sterilized.
In preferred embodiments, as in FIG. 10f, the proximal handle
portion and the proximal portion of the intermediate section are
made of a first single piece, while the distal portion of the
intermediate portion and the distal portion of the device are made
of a second single piece. In this embodiment, all of the portions
of the first longitudinal member are disposed on the upper portion
of the device.
In other embodiments, as in FIG. 10e (FIG. 3--DEP0809), the second
single piece is shaped so as to cross over the fourth pivot, so
that the first longitudinal member comprises the upper proximal
handle, the upper intermediate portion, and the lower distal
portion.
Typically, the thickness and spacing of the distal tips are
predetermined to fit snugly within a typical collapsed disc space.
In this condition, the first change in distance between the
distracting tips produces a corresponding change in the height of
the disc space. However, if the tips are undersized (i.e., the tips
are relatively small so that their initial distraction does not
distract the disc space, but only causes initial contact with the
opposed endplates), the force required to make this initial contact
should be substracted from the ultimate force measurement.
Now referring to FIG. 11, there is provided a plurality of endplate
trials 141 used with a posterior approach cage. These trials are
used to assess the dimensions of the vertebral endplates against
which the cage will seat in order to select the appropriate size
for an endplate of the cage of the present invention. These trials
can be made with varying levels of flexibility in order to allow
access around the local tissue and to access the exposed vertebral
body endplate.
Now referring to FIG. 12, there is provided a graft loading block
143 having a plurality of recesses 145 conforming to the shapes of
various size cages. The surgeon puts the cage into this block
during graft loading in order to enhance the stability of the
loading procedure.
Now referring to FIG. 13, there is provided a bone tamp 147, which
is used to pack the bone graft into the cage after it has been
loaded into the cage.
Now referring to FIG. 14, there is provided a grabber anti-torque
instrument 149. The function of the grabber anti-torque instrument
is to stabilize the implant when the set screw is loosened for
retraction and to remove the implant from the site.
Now referring to FIGS. 15a and 15b, there is provided a pair of
positioning impactors 151. These instruments may be used to gently
reposition the implant.
In some embodiments, the graft window of the present invention is
used to a deliver either a bone cement or a bone-forming agent into
the cage. The bone cement may be any material typically used to
augment vertebral bodies, including acrylic-based bone cements
(such as PMMA-based bone cements), pastes comprising bone particles
(either mineralized or demineralized or both; and ceramic-based
bone cements (such as HA and TCP-based pastes). In some
embodiments, the bone cement comprises the bone cement disclosed in
WO 02/064062 (Voellmicke).
For the purposes of the present invention, the terms "bone-forming
agent" and "bone growth agent" are used interchangeably. Typically,
the bone-forming agent may be:
a) a growth factor (such as an osteoinductive or angiogenic
factor),
b) osteoconductive (such as a porous matrix of granules),
c) osteogenic (such as viable osteoprogenitor cells), or
d) plasmid DNA.
In some embodiments, the formulation comprises a liquid carrier,
and the bone forming agent is soluble in the carrier.
In some embodiments, the bone forming agent is a growth factor. As
used herein, the term "growth factor" encompasses any cellular
product that modulates the growth or differentiation of other
cells, particularly connective tissue progenitor cells. The growth
factors that may be used in accordance with the present invention
include, but are not limited to, members of the fibroblast growth
factor family, including acidic and basic fibroblast growth factor
(FGF-1 and FGF-2) and FGF-4; members of the platelet-derived growth
factor (PDGF) family, including PDGF-AB, PDGF-BB and PDGF-AA; EGFs;
VEGF; members of the insulin-like growth factor (IGF) family,
including IGF-I and -II; the TGF-.beta. superfamily, including
TGF-.beta.1, 2 and 3; osteoid-inducing factor (OIF), angiogenin(s);
endothelins; hepatocyte growth factor and keratinocyte growth
factor; members of the bone morphogenetic proteins (BMPs) BMP-1,
BMP-3, BMP-2, OP-1, BMP-2A, BMP-2B, BMP-7 and BMP-14, including
MP-52; HBGF-1 and HBGF-2; growth differentiation factors (GDFs),
including GDF-5, members of the hedgehog family of proteins,
including indian, sonic and desert hedgehog; ADMP-1; bone-forming
members of the interleukin (IL) family; GDF-5; and members of the
colony-stimulating factor (CSF) family, including CSF-1, G-CSF, and
GM-CSF; and isoforms thereof.
In some embodiments, the growth factor is selected from the group
consisting of TGF-.beta., bFGF, and IGF-1. These growth factors are
believed to promote the regeneration of bone. In some embodiments,
the growth factor is TGF-.beta.. More preferably, TGF-.beta. is
administered in an amount of between about 10 ng/ml and about 5000
ng/ml, for example, between about 50 ng/ml and about 500 ng/ml,
e.g., between about 100 ng/ml and about 300 ng/ml.
In some embodiments, platelet concentrate is provided as the bone
forming agent. In one embodiment, the growth factors released by
the platelets are present in an amount at least two-fold (e.g.,
four-fold) greater than the amount found in the blood from which
the platelets were taken. In some embodiments, the platelet
concentrate is autologous. In some embodiments, the platelet
concentrate is platelet rich plasma (PRP). PRP is advantageous
because it contains growth factors that can restimulate the growth
of the bone, and because its fibrin matrix provides a suitable
scaffold for new tissue growth.
In some embodiments, the bone forming agent comprises an effective
amount of a bone morphogenic protein (BMP). BMPs beneficially
increasing bone formation by promoting the differentiation of
mesenchymal stem cells (MSCs) into osteoblasts and their
proliferation.
In some embodiments, between about 1 ng and about 10 mg of BMP are
intraosseously administered into the target bone. In some
embodiments, between about 1 microgram (.mu.g) and about 1 mg of
BMP are intraosseously administered into the target bone.
In some embodiments, the bone forming agent comprises an effective
amount of a fibroblast growth factor (FGF). FGF is a potent mitogen
and is angiogenic, and so attracts mesenchymal stem cells to the
target area. It is further believed that FGF stimulates osteoblasts
to differentiate into osteocytes.
In some embodiments, the FGF is acidic FGF (aFGF).
In some embodiments, the FGF is basic FGF (bFGF).
In some embodiments, between about 1 microgram (.mu.g) and about
10,000 .mu.g of FGF are intraosseously administered into the target
bone. In some embodiments, between about 10 .mu.g and about 1,000
.mu.g of FGF are intraosseously administered into the target bone.
In some embodiments, between about 50 .mu.g and about 600 .mu.g of
FGF are intraosseously administered into the target bone.
In some embodiments, between about 0.1 and about 4 mg/kg/day of FGF
are intraosseously administered into the target bone. In some
embodiments, between about 1 and about 2 mg/kg/day of FGF are
intraosseously administered into the target bone.
In some embodiments, FGF is intraosseously administered into the
target bone in a concentration of between about 0.1 mg/ml and about
100 mg/ml. In some embodiments, FGF is intraosseously administered
into the target bone in a concentration of between about 0.5 mg/ml
and about 30 mg/ml. In some embodiments, FGF is intraosseously
administered into the target bone in a concentration of between
about 1 mg/ml and about 10 mg/ml.
In some embodiments, FGF is intraosseously administered into the
target bone in an amount to provide a local tissue concentration of
between about 0.1 mg/kg and about 10 mg/kg.
In some embodiments, the formulation comprises a hyaluronic acid
carrier and bFGF. In some embodiments, formulations described in
U.S. Pat. No. 5,942,499 ("Orquest") are selected as FGF-containing
formulations.
In some embodiments, the bone forming agent comprises an effective
amount of insulin-like growth factor. IGFs beneficially increase
bone formation by promoting mitogenic activity and/or cell
proliferation.
In some embodiments, the bone forming agent comprises an effective
amount of parathyroid hormone (PTH). Without wishing to be tied to
a theory, it is believed that PTH beneficially increases bone
formation by mediating the proliferation of osteoblasts.
In some embodiments, the PTH is a fragment or variant, such as
those taught in U.S. Pat. No. 5,510,370 (Hock) and U.S. Pat. No.
6,590,081 (Zhang), and published patent application 2002/0107200
(Chang), the entire contents of which are incorporated herein in
their entirety. In one embodiment, the PTH is PTH (1-34)
(teriparatide), e.g., FORTEO.RTM. (Eli Lilly and Company). In some
embodiments, the BFA is a parathyroid hormone derivative, such as a
parathyroid hormone mutein. Examples of parathyroid muteins are
discussed in U.S. Pat. No. 5,856,138 (Fukuda), the entire contents
of which are incorporated herein in its entirety.
In some embodiments, the bone forming agent comprises an effective
amount of a statin. Without wishing to be tied to a theory, it is
believed that statins beneficially increase bone formation by
enhancing the expression of BMPs.
In some embodiments, the bone forming agent is a porous matrix, and
is preferably injectable. In some embodiments, the porous matrix is
a mineral. In one embodiment, this mineral comprises calcium and
phosphorus. In some embodiments, the mineral is selected from the
group consisting of calcium phosphate, tricalcium phosphate and
hydroxyapatite. In one embodiment, the average porosity of the
matrix is between about 20 and about 500 .mu.m, for example,
between about 50 and about 250 .mu.m. In yet other embodiments of
the present invention, in situ porosity is produced in the injected
matrix to produce a porous scaffold in the injected fracture
stabilizing cement. Once the in situ porosity is produced in the
target tissue, the surgeon can inject other therapeutic compounds
into the porosity, thereby treating the surrounding tissues and
enhancing the remodeling process of the target tissue and the
injectable cement.
In some embodiments, the mineral is administered in a granule form.
It is believed that the administration of granular minerals
promotes the formation of the bone growth around the minerals such
that osteointegration occurs.
In some embodiments, the mineral is administered in a
settable-paste form. In this condition, the paste sets up in vivo,
and thereby immediately imparts post-treatment mechanical support
to the fragile OP body.
In another embodiment, the treatment is delivered via injectable
absorbable or non-absorbable cement to the target tissue. The
treatment is formulated using bioabsorbable macro-sphere
technologies, such that it will allow the release of the bone
forming agent first, followed by the release of the anti-resorptive
agent. The cement will provide the initial stability required to
treat pain in fractured target tissues. These tissues include, but
are not limited to, hips, knee, vertebral body fractures and iliac
crest fractures. In some embodiments, the cement is selected from
the group consisting of calcium phosphate, tricalcium phosphate and
hydroxyapatite. In other embodiments, the cement is any hard
biocompatible cement, including PMMA, processed autogenous and
allograft bone. Hydroxylapatite is a preferred cement because of
its strength and biological profile. Tricalcium phosphate may also
be used alone or in combination with hydroxylapatite, particularly
if some degree of resorption is desired in the cement.
In some embodiments, the porous matrix comprises a resorbable
polymeric material.
In some embodiments, the bone forming agent comprises an injectable
precursor fluid that produces the in situ formation of a
mineralized collagen composite. In some embodiments, the injectable
precursor fluid comprises: a) a first formulation comprising an
acid-soluble type I collagen solution (preferably between about 1
mg/ml and about 7 mg/ml collagen) and b) a second formulation
comprising liposomes containing calcium and phosphate.
Combining the acid-soluble collagen solution with the calcium- and
phosphate-loaded liposomes results in a liposome/collagen precursor
fluid, which, when heated from room temperature to 37.degree. C.,
forms a mineralized collagen gel.
In some embodiments, the liposomes are loaded with
dipalmitoylphosphatidylcholine (90 mol %) and dimyristoyl
phosphatidylcholine (10 mol %). These liposomes are stable at room
temperature but form calcium phosphate mineral when heated above
35.degree. C., a consequence of the release of entrapped salts at
the lipid chain melting transition. One such technology is
disclosed in Pederson, Biomaterials 24: 4881-4890 (2003), the
specification of which is incorporated herein by reference in its
entirety.
Alternatively, the in situ mineralization of collagen could be
achieved by an increase in temperature achieved by other types of
reactions including, but not limited to, chemical, enzymatic,
magnetic, electric, photo- or nuclear. Suitable sources thereof
include light, chemical reaction, enzymatically controlled reaction
and an electric wire embedded in the material. To further elucidate
the electric wire approach, a wire (which can be the reinforcement
rod) can first be embedded in the space, heated to create the
calcium deposition, and then withdrawn. In some embodiments, this
wire may be a shape memory such as nitinol that can form the shape.
Alternatively, an electrically-conducting polymer can be selected
as the temperature raising element. This polymer is heated to form
the collagen, and is then subject to disintegration and resorption
in situ, thereby providing space adjacent the mineralized collagen
for the bone to form.
In one embodiment, the bone forming agent is a plurality of viable
osteoprogenitor cells. Such viable cells, introduced into the bone,
have the capability of at least partially repairing any bone loss
experienced by the bone during the osteoporotic process. In some
embodiments, these cells are introduced into the cancellous portion
of the bone and ultimately produce new cancellous bone. In others,
these cells are introduced into the cortical region and produce new
cortical bone.
In some embodiments, these cells are obtained from another human
individual (allograft), while in other embodiments, the cells are
obtained from the same individual (autograft). In some embodiments,
the cells are taken from bone tissue, while in others, the cells
are taken from a non-bone tissue (and may, for example, be
mesenchymal stem cells, chondrocytes or fibroblasts). In others,
autograft osteocytes (such as from the knee, hip, shoulder, finger
or ear) may be used.
In one embodiment, when viable cells are selected as an additional
therapeutic agent or substance, the viable cells comprise
mesenchymal stem cells (MSCs). MSCs provide a special advantage for
administration into an uncoupled resorbing bone because it is
believed that they can more readily survive the relatively harsh
environment present in the uncoupled resorbing bone; that they have
a desirable level of plasticity; and that they have the ability to
proliferate and differentiate into the desired cells.
In some embodiments, the mesenchymal stem cells are obtained from
bone marrow, such as autologous bone marrow. In others, the
mesenchymal stem cells are obtained from adipose tissue, preferably
autologous adipose tissue.
In some embodiments, the mesenchymal stem cells injected into the
bone are provided in an unconcentrated form, e.g., from fresh bone
marrow. In others, they are provided in a concentrated form. When
provided in concentrated form, they can be uncultured. Uncultured,
concentrated MSCs can be readily obtained by centrifugation,
filtration, or immuno-absorption. When filtration is selected, the
methods disclosed in U.S. Pat. No. 6,049,026 ("Muschler"), the
specification of which is incorporated herein by reference in its
entirety, can be used. In some embodiments, the matrix used to
filter and concentrate the MSCs is also administered into the
uncoupled resorbing bone.
In some embodiments, bone cells (which may be from either an
allogeneic or an autologous source) or mesenchymal stem cells, may
be genetically modified to produce an osteoinductive bone anabolic
agent which could be chosen from the list of growth factors named
herein. The production of these osteopromotive agents may lead to
bone growth.
In some embodiments, the osteoconductive material comprises calcium
and phosphorus. In some embodiments, the osteoconductive material
comprises hydroxyapatite. In some embodiments, the osteoconductive
material comprises collagen. In some embodiments, the
osteoconductive material is in a particulate form.
Recent work has shown that plasmid DNA will not elicit an
inflammatory response as does the use of viral vectors. Genes
encoding bone (anabolic) agents such as BMP may be efficacious if
injected into the uncoupled resorbing bone. In addition,
overexpression of any of the growth factors provided herein or
other agents which would limit local osteoclast activity would have
positive effects on bone growth. In one embodiment, the plasmid
contains the genetic code for human TGF-.beta. or erythropoietin
(EPO).
Accordingly, in some embodiments, the additional therapeutic agent
is selected from the group consisting of viable cells and plasmid
DNA.
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