U.S. patent application number 09/778046 was filed with the patent office on 2001-09-06 for selective uptake of materials by bone implants.
Invention is credited to Sander, Tom.
Application Number | 20010020188 09/778046 |
Document ID | / |
Family ID | 29553678 |
Filed Date | 2001-09-06 |
United States Patent
Application |
20010020188 |
Kind Code |
A1 |
Sander, Tom |
September 6, 2001 |
Selective uptake of materials by bone implants
Abstract
This invention provides a novel unitary bone implant having at
least one rigid, mineralized bone segment, which may be machined to
include threads, grooves, a driver head, perforations, a recess or
a symmetric or asymmetric shape, and a flexible, demineralized
segment, which may also be machined to any desired shape prior to
demineralization, or after demineralization. The implant of this
invention has wide orthopedic applicability, including but not
limited to repair or replacement of ligaments, tendons and joints
and for inducing vertebral fusions and fractured bone repair. In a
particular embodiment of this invention, selective uptake of
biologically active or inactive materials into the segmentally
demineralized portion of the implant is disclosed.
Inventors: |
Sander, Tom; (Alachua,
FL) |
Correspondence
Address: |
Gerard H. Bencen
Bencen & Van Dyke, P.A.
1630 Hillcrest Street
Orlando
FL
32803
US
|
Family ID: |
29553678 |
Appl. No.: |
09/778046 |
Filed: |
February 5, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09778046 |
Feb 5, 2001 |
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09585772 |
Jun 2, 2000 |
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09585772 |
Jun 2, 2000 |
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09518000 |
Mar 2, 2000 |
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09518000 |
Mar 2, 2000 |
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09417401 |
Oct 13, 1999 |
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09518000 |
Mar 2, 2000 |
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08958364 |
Oct 27, 1997 |
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6090998 |
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Current U.S.
Class: |
623/23.57 ;
424/423; 623/23.6; 623/23.63 |
Current CPC
Class: |
A61F 2/2875 20130101;
A61F 2002/30179 20130101; A61F 2002/30787 20130101; A61F 2002/30261
20130101; A61F 2002/30772 20130101; A61F 2250/0019 20130101; A61L
27/3843 20130101; A61F 2230/0019 20130101; A61F 2230/0006 20130101;
A61L 27/3683 20130101; A61B 17/06166 20130101; A61F 2002/30266
20130101; A61F 2002/30677 20130101; A61F 2002/30892 20130101; A61L
27/3662 20130101; A61L 2300/252 20130101; A61F 2002/30228 20130101;
A61L 27/3834 20130101; A61L 2430/02 20130101; A61F 2002/30293
20130101; A61F 2002/30113 20130101; A61F 2002/3082 20130101; A61F
2002/087 20130101; A61L 27/365 20130101; A61F 2002/30131 20130101;
A61F 2002/30879 20130101; A61B 17/86 20130101; A61F 2/08 20130101;
A61F 2/30965 20130101; A61F 2002/30059 20130101; A61F 2002/30828
20130101; A61F 2002/30784 20130101; A61L 27/3645 20130101; A61F
2002/302 20130101; A61F 2002/30009 20130101; A61F 2002/30594
20130101; A61L 27/3608 20130101; A61F 2002/0858 20130101; A61F
2/4241 20130101; A61F 2002/30153 20130101; A61L 2300/41 20130101;
A61F 2002/30265 20130101; A61F 2002/30224 20130101; A61F 2230/0082
20130101; A61F 2230/0091 20130101; A61F 2230/0013 20130101; A61F
2002/30563 20130101; A61L 27/3847 20130101; A61F 2002/30904
20130101; A61F 2002/4251 20130101; A61L 27/386 20130101; A61F
2002/30774 20130101; A61F 2002/3023 20130101; A61F 2002/30831
20130101; A61F 2/2846 20130101; A61F 2002/30125 20130101; A61F
2002/30235 20130101; A61F 2230/0008 20130101; A61F 2/0811 20130101;
A61F 2230/0023 20130101; A61F 2230/0065 20130101; A61F 2240/001
20130101; A61F 2230/0052 20130101; A61F 2/4455 20130101; A61F 2/28
20130101; A61F 2002/0829 20130101; A61F 2002/30156 20130101; A61F
2230/0069 20130101; A61L 27/54 20130101; A61F 2002/3085 20130101;
A61F 2002/2839 20130101; A61F 2002/30878 20130101; A61F 2230/0058
20130101; A61F 2/442 20130101; A61F 2/30771 20130101; A61F
2002/30016 20130101; A61F 2002/30971 20130101; A61L 2300/258
20130101; A61L 2300/406 20130101; A61F 2/4465 20130101; A61F 2/3094
20130101; A61F 2002/2817 20130101; A61F 2002/30172 20130101; A61F
2002/4649 20130101; A61F 2250/0028 20130101; A61F 2002/0882
20130101 |
Class at
Publication: |
623/23.57 ;
623/23.6; 623/23.63; 424/423 |
International
Class: |
A61F 002/28 |
Claims
What is claimed is:
1. A segmentally demineralized bone implant designed for
implantation in a patient, said implant comprising at least one
mineralized segment, and at least one demineralized segment,
wherein said demineralized segment is modified by selective uptake
of a cell, or biologically active or inert molecule.
2. The implant according to claim 1 wherein said demineralized
segment is modified by selective uptake of cells, blood components,
growth factors, nucleic acids, proteins, peptides, antibiotics,
antineoplastics, anti-inflammatory compounds, and combinations
thereof.
3. The implant of claim 1, wherein said implant is derived from
cortical, corticocancellous, cancellous bone, or combinations
thereof.
4. The implant of claim 2 wherein said cells are mesenchymal stem
cells (MSC's).
5. The implant of claim 2 wherein said growth factors are bone
morphogenetic proteins, (BMPs), fibroblast growth factors (FGFs),
platelet derived growth factor (PDGF), cartilage derived
morphogenetic proteins (CDMPs), tissue derived growth factors
(TGFs), and combinations thereof.
6. The implant according to claim 2 wherein said biologically
active compound is selected from the group consisting of nucleic
acids, proteins, peptides, antibiotics, antineoplastics,
anti-inflammatory compounds, and combinations thereof.
7. A method of repairing damaged tissue in a patient, human or
non-human, in need thereof which comprises implanting in said
patient an implant comprising a segmentally demineralized bone
implant designed for implantation in a patient, said implant
comprising at least one mineralized segment, and at least one
demineralized segment, wherein said demineralized segment is
modified by selective uptake of a cell, or biologically active or
inert molecule.
8. A method of making a biological implant which comprises
segmentally demineralizing a portion of bone, either before or
after machining said bone into any desirable shape for implantation
into a patient, human or animal, in need thereof, contacting said
segmentally demineralized implant with a composition containing a
substance the infusion of which into said demineralized portion of
said bone implant is desired, and implanting the thus-treated
implant into said patient in need thereof.
9. An implant made by the process of claim 8.
10. A method of treating a disease condition which comprises
removal of diseased or damaged tissue and implanting in place
thereof a segmentally demineralized bone implant designed for
implantation in a patient, said implant comprising at least one
mineralized segment, and at least one demineralized segment,
wherein said demineralized segment is modified by selective uptake
of a cell, or biologically active or inert molecule, or
combinations thereof.
11. The method according to claim 10 wherein said biologically
active molecule is an antibiotic, an antineoplastics, an
anti-inflammatory, an antiviral, an antifungal, or a combination of
such molecules.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of application
Ser. No. 09/585,772, filed on Jun. 2, 2000, pending Attorney Docket
Number RTI-1051C, which was a continuation-in-part of application
Ser. No. 09/518,000 filed Mar. 2, 2000, pending Attorney Docket
Number RTI-105-IB, which was a continuation-in-part of application
Ser. No. 09/417,401 filed Oct. 13, 1999, pending Attorney Docket
Number RTI-105IA and application Ser. No. 08/958,364, filed on Oct.
27, 1997, now U.S. Pat. No. 6,090,998, the subject matter and
disclosure of all of which is hereby incorporated herein by
reference as if fully set forth herein.
FIELD OF THE INVENTION
[0002] This invention relates to a device made from segmentally
demineralized and appropriately shaped and machined bone for
implantation as a ligament, tendon, support or in any other
application in which an implant having at least one rigid segment
and at least one flexible segment, is required. In particular, this
invention disclosure relates to the novel selective uptake of
materials by bone implants of this type by modifying the
mineralization status of various portions of bone implants.
BACKGROUND
[0003] There is a continuing need in the art for biologically
acceptable ligament or tendon replacements. Various efforts have
been made in the art to accommodate this need. For example, in U.S.
Pat. No. 5,053,049, a flexible prosthesis of predetermined shape
and a process for making said prosthesis was disclosed. According
to that disclosure, a flexible biocompatible and non-antigenic
prosthesis for replacement of a cartilaginous part was prepared by
machining bone into a desired shape corresponding to the shape of a
cartilaginous body part to be replaced, demineralization of the
bone to impart flexibility, and tanning to reduce antigenicity.
There was no disclosure or suggestion of using the demineralized
bone as a tendon or ligament replacement.
[0004] In U.S. Pat. No. 5,092,887, a method for replacement or
augmentation of a damaged fibrous connective tissue was disclosed
wherein a ligament made from a segment of bone that had been
demineralized was attached between first and second body parts.
There was no disclosure or suggestion of machining the bone prior
to demineralization to produce fixation ends thereon, and
demineralization of only a segment of the thus machined bone to
produce a flexible segment, while leaving the machined attachment
ends in a fully mineralized and rigid state for fixation directly
to bone adapted to receive such fixation ends. The disclosure in
the 5,092,887 patent with respect to its discussion of background
art and methods of demineralization of bone is hereby incorporated
by reference.
[0005] In particular, the present invention is directed to methods
of selective update of materials into bone for implantation. The
selective uptake of almost any material has been found to be
enhanced by selectively demineralizing that portion of bone and
then contacting the thus-treated portion of bone with a liquid
milieu containing the material the selective uptake of which into
the bone implant is desired. According to this invention, any of a
number of different materials may be selectively taken up,
absorbed, infused or otherwise contained by segmentally
demineralized bone. Thus, those skilled in the art will know, based
on the instant disclosure, which shows selective uptake of
osteogenic progenitor cells, hematopoietic cells, growth factors,
antibiotics, nucleic acids and the like, that any desired material
may be induced to selectively be taken up by demineralized portions
of bone implants.
SUMMARY OF THE INVENTION
[0006] This invention provides a novel bone implant having at least
one rigid, mineralized bone segment, which may be machined to
include threads, grooves, a driver head, a recess or a symmetric or
asymmetric shape, and at least one flexible, demineralized segment,
which may also be machined to any desired shape prior to
demineralization, or after demineralization. According to
alternative aspects, the subject implants may comprise only
demineralized portions or mineralized portions, wherein the
demineralized or mineralized portions have utility separately, or
are brought into association together. The subject implants are
preferably made of cortical, cortico-cancellous, or cancellous
bone. It is to be understood that the type of bone used to make the
subject bone implants will depend on the intended end use of the
implant. Factors to be considered in determining the type of bone
to use include, but are not limited to, strength, porosity, and/or
flexibility, the effect of which will be apparent to those skilled
in the art in view of the teachings herein. In particular, in this
aspect of the invention, the selectively demineralized portions of
the bone implant are contacted with materials, compositions,
compounds, solutions, cells or the like, the selective uptake of
which is enhanced in those portion of the implant that are
demineralized. The result of such uptake is the conferral on the
selectively demineralized portions of the bone implant of
particular properties, such as the more rapid remodeling of the
bone implant into autogenous bone, by virtue of selective uptake of
bone progenitor cells, or the more rapid remodeling of the bone
into flexible connective tissue, such as cartilage or ligaments or
tendons, through selective uptake of chondrocytes, or fibroblasts,
or the like, depending on whether the implant portion is desired to
remodel into one tissue type or another.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] FIG. 1 provides a view of a first embodiment of the implant
of this invention in which a rigid bone segment is machined to
exhibit threads on each end (FIG. 1A), and which is then
demineralized only in the internal section to provide a flexible
segment between the machined ends (FIG. 1C); FIG. 1B provides a
view of an alternate embodiment in which one end of the implant has
a rigid fixation bone block; FIG. 1D shows an end-on view of a
cannulated embodiment of the implant of this invention.
[0008] FIG. 2 provides a view of a second embodiment of the implant
of this invention in which a rigid bone segment is machined to
exhibit threads on one end and an attachment hole at the other
(FIG. 2A), and which is then demineralized on the attachment hole
end of the implant to provide a flexible segment, while retaining
the threaded segment as a rigid member (FIG. 2B). A partial
cannulation of the implant is shown in end-on (FIG. 2C), top (FIG.
2D) and side views (FIG. 2E).
[0009] FIG. 3 provides a view of a third embodiment of the implant
of this invention in which a rigid bone segment is machined to
exhibit a fixation block at each end of the implant (FIG. 3A), and
which is then demineralized between the two ends to provide a
flexible segment between the machined fixation block ends (FIG.
3B).
[0010] FIG. 4 provides a view of a fourth embodiment of the implant
of this invention in which a rigid bone segment is machined to
exhibit a fixation block at one end and an attachment hole (FIG.
4A) or several holes or perforations (FIG. 4B) at the other, and
which is then demineralized at the end bearing the attachment
hole(s) (FIGS. 4C and 4D) to provide a flexible segment, while
retaining the fixation block end as a rigid member.
[0011] FIG. 5 shows one method of implantation of the implant of
this invention in which fixation screws are utilized to retain the
implant of this invention in place either by locking the implant in
place through holes in the rigid segment of the implant (FIG. 5A),
or by locking the implant into place at the rigid end of the
implant via a tapped recess (FIGS. 5B and 5C).
[0012] FIG. 6 shows an embodiment of this invention in which the
implant is a femoral ring (FIG. 6A) in which the upper and lower
ends of the ring are retained in a rigid, mineralized state and
which may be machined to exhibit a thread or a groove, and the
internal segment of the implant is demineralized to exhibit a soft
spongy layer to provide flexible support upon insertion of this
embodiment of the invention between adjacent vertebral bodies;
alternatively, the upper, lower or both segments may be
demineralized and the internal segment may be retained in a
mineralized state; FIG. 6B shows this implant having angled faces;
FIG. 6C shows this implant machined as a wedge.
[0013] FIG. 7 shows various cross-sections (FIG. 7A, spherical;
FIG. 7B, elliptical; FIG. 7C, rectangular; FIG. 7D, cross-shaped)
for the mineralized or demineralized segment of the implant of this
invention.
[0014] FIG. 8 depicts one embodiment of a prosthetic joint
according to this invention having pointed projections for
replacement of a joint (FIG. 8A) or for insertion between vertebrae
(FIG. 8B).
[0015] FIG. 9 depicts a flexible implant according to this
invention for contoured repair of bone defects, including but not
limited to craniomaxillofacial defects, including a first
"pizza-shaped implant" (FIG. 9A), a second "pizza-shaped implant"
(FIG. 9B), and a wrap implant having alternating mineralized and
demineralized segments (FIG. 9C).
[0016] FIG. 10A depicts a first embodiment and FIG. 10B depicts a
second embodiment of an anterior longitudinal ligament replacement
for limiting motion between adjacent vertebrae to be fused.
[0017] FIG. 11 depicts a band for limiting the motion and reducing
the degradation of vertebrae juxtaposed to vertebrae undergoing
fusion (i.e. as a spinal tension band) or for being affixed to any
other anatomical structures to minimize motion of such structures
in relation to each other.
[0018] FIG. 12 depicts a perforated sheet comprising mineralized
and demineralized bone for use as a "mesh", such as for use in a
dressing or to retain particulate matter.
[0019] FIG. 13 depicts a cortical bone screw comprising at least a
portion thereof which is demineralized or partially
demineralized.
[0020] FIG. 14A shows a side view, FIG. 14B shows a rear view, and
FIG. 14C shows a frontal view of an implant that is particularly
suited for implantation into the intervertebral space.
[0021] FIG. 15 depicts an embodiment that is particularly suited
for implantation into the intervertebral space.
[0022] FIG. 16A depicts an embodiment useful as a delivery vehicle
comprising a mineralized region and a demineralized region, wherein
the demineralized region contains a biologically active substance.
FIG. 16B shows the embodiment as conformed around an internal
structure.
[0023] FIG. 17 depicts an embodiment that is flexible and has
associated therewith a support structure that confers the ability
to maintain a predetermined shape.
[0024] FIG. 18 depicts an embodiment in the form of a plate which
has mineralized regions formed thereon for providing a secure
substrate for an attachment means.
[0025] FIG. 19A depicts a top view, and FIG. 19B depicts a side
view portion of an embodiment having a demineralized cortex and
mineralized rows disposed thereon.
[0026] FIG. 20 depicts a 3-D view of an embodiment that comprises a
demineralized cortex and a plurality of mineralized projections
extending from the demineralized cortex.
[0027] FIG. 21 demonstrates an implant with at least one and
optionally a plurality of lumens running longitudinally
therethrough.
[0028] FIG. 22 is a representation of a segmentally demineralized
bone implant in which cellular material has been selectively taken
up by the portion of the bone implant that is demineralized.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0029] This invention provides a biologically acceptable ligament,
tendon, support or other implant for replacement of damaged
ligaments, tendons, vertebral disks and the like, wherein there is
a need for an implant having both a rigid machined portion or
segment as well as a flexible, demineralized portion or segment.
According to one embodiment of this invention, a segment of
preferably cortical bone is machined into a desired shape, with at
least one end being machined so as to provide a means for fixation
of that end directly to a bone machined in a complementary fashion.
Referring to FIG. 1A, a first embodiment of the implant of this
invention 100 is shown in which the ends 101 and 102 of the implant
are machined so as to exhibit a thread, and the bone to which the
implant is to be affixed is tapped to exhibit a receiving thread
complementary to the thread on the implant end. Alternatively, the
threaded ends 101, 102 may be self-tapping, thereby eliminating the
need to tap the receiving bone. A simple hole, of a diameter
slightly smaller than the diameter of the threaded implant ends,
may be drilled or produced by like means to receive the threaded
implant end. An internal segment 103 of the implant is
demineralized to provide a flexible segment of the implant, while
transition zones 104, 105 are provided wherein the level of
mineralization of the bone gradually changes from a fully
mineralized to a demineralized state. In a preferred version of
this embodiment of the invention, the two ends 101, 102 of the
implant are machined to exhibit threads such that clockwise or
counterclockwise rotation of the entire implant results in
simultaneous insertion of both ends of the implant or extraction of
both ends of the implant into or out of complementarily machined
bones to which the implant is to be affixed, without kinking of the
flexible segment 103 of the implant. In FIG. 1B, an alternate
embodiment is shown wherein one of the ends, 101', is not threaded,
but is machined to any desirable shape, such as a fixation block,
such that the threaded end 102 may be threaded into the receiving
bone, while the fixation block 101' is affixed in place by
interference screws or like means known in the art. In yet a
further embodiment, shown in FIG. 1D, the entire implant is
machined so as to exhibit a cannulation 110 throughout its length
or a portion thereof. In this fashion, the implant may be inserted
over a guide-wire or like guide means. Alternatively, the aspect
110 may be an internal thread capable of receiving a threaded
retention screw. It will be recognized that features disclosed for
this embodiment or any of the other embodiments of the invention
may be applied to other embodiments of this invention, to produce
embodiments exhibiting a variety of combinations of different
features disclosed for each of the individually disclosed
embodiments.
[0030] In a further embodiment of this invention 200 shown in FIG.
2, only one end 202 of the implant 200 is machined to exhibit a
thread or another machined feature, while the other end 201 may be
machined to exhibit a fixation hole 210 or a similar feature, which
permits for suturing or otherwise fixing that end to a ligament or
a tendon. A transition zone 204 from a mineralized to a
demineralized state is provided, as is a flexible segment of the
implant 203. In FIGS. 2C-E, there are shown an end-on view, a side
view and a top view, respectively. In this embodiment of the
invention, an optional cannulation 220 is shown, permitting
threading of the machined portion 202 of the implant over a
guide-wire, for example, while not interfering with the flexible,
demineralized segment 203 of the implant.
[0031] In a further embodiment 300 of this invention shown in FIG.
3, the implant may be used to replace a ligament. In this
embodiment, two transition zones 304, 305 from the flexible segment
303 to terminally mineralized fixation blocks 301, 302 are
provided. The fixation blocks 301 and 302 each have a canal 306,
307 machined therein for receiving a fixation screw or pin. The
mineralized sections 302, 303 may be machined into any desired form
of an anchoring fixture. The anchoring fixture may contain a screw
thread, a hole for receipt of an anchoring pin or an anchoring
screw, or a screw that rotates within a sleeve.
[0032] In the embodiment 400 shown in FIG. 4A, the implant is used
for repair or replacement of a tendon. In this embodiment, only one
end 402 of the implant 400 is machined for fixation in a bone, and
the second end 401 of the implant is adapted to a variety of
shapes, terminating in a means, such as a threadable hole 410, for
fixation of that end to bone, muscle, tendon or ligament. In an
alternate embodiment shown in FIGS. 4B and 4D, the end 401' is
machined to exhibit a plurality of holes or perforations, 410' ,
such that end 401' may be sutured to a receiving biological
structure, such as a muscle, ligament, tendon, bone or the
like.
[0033] In FIG. 5, one method of implantation of the implant 500 of
this invention is shown in which fixation screws 553 are utilized
to retain an embodiment of the implant 500 of this invention in a
machined slot 551 in a bone 550 either by locking the implant in
place (FIG. 5A) through holes 552 in the rigid segment 501 of the
implant (FIG. 5A), or by locking the implant into place at the
rigid end 503 of the implant via a tapped recess (FIGS. 5B and 5C).
The other end of the implant 504 is demineralized, and is thus
flexible, and terminates in a hole 502 or other fixation means by
which that end of the implant is attached to bone, tendon, ligament
or muscle. As noted above, section 501 could be threaded, end 502
could be retained in a mineralized state and could be shaped as a
fixation block for retention by an interference screw, or threaded.
In addition, the implant 500 may be cannulated, with the recess 503
continuing through the entire length of the implant, or some
portion thereof.
[0034] FIG. 6A shows an embodiment of this invention in which the
implant 600 is a femoral ring member or a portion thereof wherein
the upper and lower ends or faces 602, 604 are retained in a rigid,
mineralized state and which may be machined to exhibit a thread or
a groove by means known in the art (see WO 97/25945, hereby
incorporated by reference for this purpose). The internal segment
of the implant 603 is demineralized to exhibit a soft spongy region
to provide flexible support upon insertion of this embodiment of
the invention between, for example, adjacent vertebral bodies. An
internal canal 601 is shown in the femoral ring, which derives from
the natural intramedullary canal of the bone from which the femoral
ring is obtained by substantially planar, parallel cross-cuts
across the diaphysis of a femur or like long bone. Alternatively, a
transverse cut to form a dowel which is then segmentally
demineralized is also contemplated. The canal may be left open or
filled with osteogenic factors, including but not limited to
autologous bone or marrow. Alternatively, the canal may be filled
with a carrier and growth factors, including but not limited to
bone morphogenetic proteins, demineralized bone matrix (DBM), or
any inert or biologically active substance considered beneficial
for insertion into the spine to assist in support thereof or for
fusion of adjacent vertebrae. Furthermore, the canal may retain the
natural architecture of the intramedullary canal or it may be
scraped out or otherwise modified. Those skilled in the art will
appreciate that in this embodiment of the invention, the upper end
601, the lower end 604, or both may be demineralized, while the
internal segment 603 of the implant may be maintained in a
mineralized state. It will further be appreciated that the upper
602 and lower 604 faces of the implant may not be parallel, but
rather may slope toward each other, as shown for embodiment 610 in
FIG. 6B, such that H1 is greater than H2. Furthermore, the upper
and lower faces may exhibit curvature and external features, such
as grooves, pits or protrusions to assist in the retention of the
implant when inserted between adjacent vertebrae. In an embodiment
comprising sloping upper and lower faces, the slant of the upper
and lower faces should be such that the natural lordosis of the
spinal segment into which the implant is inserted is maintained. It
will further be appreciated that the shape of the implant may
include a substantially circular, elliptical, rectangular or like
shape. As shown in FIG. 6C, the implant may comprise a portion of
the femoral ring, exhibiting a greater width W1 and a lesser width
W2. Furthermore, the upper surface, lower surface or both surfaces
may comprise features such as grooves, pits, indents, teeth or
protrusions to inhibit slippage or expulsion of the implant.
[0035] The implant of this invention comprising a segmentally
demineralized bone comprising at least one mineralized portion or
segment, and at least one flexible, demineralized portion or
segment is produced by machining a piece of preferably cortical
bone into any desired shape. The bone is preferably chosen to be
strong cortical bone, such as from the femur, tibia, fibula, radius
or ulna. The source of the donor bone may be autograft, allograft
or xenograft bone, with the appropriate cautionary steps known in
the art being taken in each case to prevent introduction into the
recipient of pathogenic or antigenic agents.
[0036] After appropriately shaping the implant bone stock, a
segment of the implant is preferably machined to exhibit a thread
or like fixation means whereby the implant may be directly affixed
to recipient bone machined in a complementary fashion. That segment
of the implant is retained in a mineralized state, by appropriately
protecting that segment of the implant with any protective device,
such as with parafilm, a rubber or latex covering, plastic wrap,
and the like. The remaining segment of the implant is then
demineralized according to methods known in the art. For example,
in the embodiment 100 of this invention shown in FIG. 1A, both ends
101, 102 may be inserted into rubber stoppers spanning the
transition zones 104, 105, and the internal segment 103, is exposed
to an acid solution of sufficient strength to leach the minerals
from that segment of the bone. A 5% acetic acid solution or a 1 N
hydrochloric acid solution may be employed, and the implant checked
periodically for the desired level of flexibility of the internal
zone 103. It is important that an excessively high concentration of
strong acid not be employed for this process, as this will result
in cleavage of the peptide bonds of the collagenous matrix within
which the minerals are deposited. Accordingly, HC1 concentrations
of between about 0.1N to 2N are acceptable, with the period of
exposure to acid being increased for the lower acid concentrations
and decreased for the higher acid concentrations. Likewise,
depending on the strength of the acid used. The transition zones
104, 105 are formed by diffusion of the acid into and diffusion of
the minerals out of the bone in that segment of the implant covered
by the protective covering. By varying the degree of
demineralization, the properties of the implant of this invention
may be altered to provide optimal strength and flexibility, as
required for the particular application for which the implant is to
be employed.
[0037] The implant of this invention may be prepared by
appropriately masking portions of the implant, using a tape,
rubber, latex or any other material which may be adhered to any
portion of the bone, to prevent demineralization of portions
thereof. Accordingly, in one embodiment of this invention, the
implant is produced by masking portions of a flat segment of
cortical bone, to form a striated "pizza-slice-shaped" implant
device, as shown in FIG. 9. According to this embodiment of the
invention, a shape, such as a substantially hexagonal piece of
cortical bone 900 is demineralized after application of masking
means 910 such that intermediate sections 920 are demineralized
while zones of mineralized bone remain where masked at 910.
Alternatively, as shown in FIG. 9B, an implant 950 is produced
wherein zones 960 are protected from the demineralizing agent
(acid, chelating agents, and the like), while areas 970 are not
protected. The result is a pizza-slice-shaped implant 950 having
flexible hinge portions with mineralized pizza-slice-shaped
portions 960 which retain mineral and rigidity. An implant such as
900 or 950 has application, for example, in the repair of
craniofacial or craniomaxillofacial defects, among other possible
applications. As a result, what is produced is either an implant
which comprises a plurality of adjacent mineralized triangular
segments, the apex of each triangle meeting at a common point and
the sides of each triangle except the base opposite the apex being
joined to each other through a demineralized hinge, or an implant
which comprises a plurality of adjacent demineralized triangular
segments, the apex of each triangle meeting at a common point and
the sides of each triangle except the base opposite the apex being
joined to each other through a mineralized hinge. It will be
understood that other shapes or forms of alternating mineralized
and demineralized bone may also be produced and used according to
this invention. Thus, for example, a "bone-wrap" 980 shown in FIG.
9C may be produced from a sheet of cortical bone with alternating
mineralized 990 and demineralized 985 zones for wrapping around a
piece of fractured bone, for example. In this way, the mineralized
portion of the bone-wrap acts as a splint while the flexible,
demineralized portion of the bone-wrap permits the implant to wrap
around the fractured bone segment. The flexibility of the implant
permits the implant to be contoured to the surface of a bone defect
area to repair such defect. Naturally, based on this disclosure,
those skilled in the art will appreciate that implants of a wide
variety of shapes, sizes and applications may be produced in a
similar manner wherein a portion of the implant retains a rigid
mineralized portion and a portion of the implant is at least
partially demineralized to produce a flexible portion of the
implant. Thus, sheets of bone, partially demineralized wrapping
sheets and the like are all variations on this theme which come
within the scope of the instant invention.
[0038] In a further aspect of this invention, a partial
demineralization of the surface of bone implants has been found to
be beneficial in that modification of the stress-fracture behavior
of the bone may thus be achieved. Accordingly, depletion of up to
about 25 percent of the natural bone mineral may be achieved by
limited demineralization to break up the bone crystal structure in
the partially demineralized portion of the implant. As a result,
reduction in the variability of the stress load at which bone
fractures upon stress of the bone has been noted, even when as
little as a one percent reduction in the bone mineral content is
used. This observation may be combined with embodiments of the
implant of this invention wherein a portion of the implant is
maintained in a rigid, mineralized state, while at least one
portion of the implant is demineralized or partially
demineralized.
[0039] It will further be appreciated that the implant of this
invention may be further treated by tanning or other means known in
the art to reduce the antigenicity of the implant. For example,
glutaraldehyde treatment (see U.S. Pat. No. 5,053,049, hereby
incorporated by reference for this purpose), may be used.
Alternatively, or in addition, the implant may be subjected to
treatment with chaotropic agents, including but not limited to
urea, guanidine hydrochloride, combinations thereof and like
agents, to remove noncovalent immunogens. Treatment with reducing
agents, detergents, chelating agents and the like may also be
beneficially applied, depending on the nature of the bone implant
and its source. For example, where xenograft bone is used as the
material for implant production, reduction in the antigenicity of
the bone becomes much more important than if autograft or allograft
bone is used.
[0040] In FIG. 7, various cross-sectional shapes of the implant of
this invention are shown. Thus, in FIG. 7A, a cylindrical
cross-section is shown. It will be recognized that various
diameters, from as small as 0.5 mm or smaller to as large as 10 mm,
or in certain applications, even larger, may be desirable. In FIG.
7B, an oval cross-section is provided. In FIG. 7C, a flat cross
section is provided. In FIG. 7D, a cross-shaped cross-section is
provided. Those skilled in the art will recognize that the
disclosure of this invention permits for essentially any desirable
shape to be generated for the flexible or rigid segments of the
implant of this invention, and such variations come within the
scope of this disclosure and the appended claims. In forming the
various crosssectional shapes suggested herein, it is desirable
that a smooth transition occurs between the rigid end(s) of the
implant and the flexible segment. This is accomplished by
appropriately machining the end(s) such that a taper into the
flexible segment occurs, and by carefully controlling the
demineralization process to ensure a graded demineralization from
the fully mineralized segment to the demineralized segment.
[0041] It will further be understood from the foregoing disclosure
that the implant of this invention may be appropriately fashioned
for a wide diversity of applications. For example, an implant of
this invention may be applied to repair of ligaments or tendons in
the hand, elbow, knee, foot, ankle or any other anatomical location
as needed. Furthermore, the implant of this invention may be
applied to replacement any of a variety of joints. Methods and
implant shapes known in the art for joint replacement, (see, for
example U.S. Pat. Nos. 4,871,367; Des. 284,099; Des. 277,784; Des.
277,509; 3,886,600; 3,875,594; 3,772,709; 5,484,443; 5,092,896;
5,133,761; 5,405,400; and 4,759,768; all of which are herein
incorporated by reference for their teachings of various
considerations applicable to joint prosthetic implants), may be
fashioned according to and replaced by the implant of the instant
disclosure. Thus, in one embodiment of this invention, a piece of
cortical bone is shaped so as to form a surgically implantable
prosthetic joint having a load distributing flexible hinge,
analogous to that disclosed in U.S. Pat. No. 3,875,594 (which was
made from molded silicone rubber). According to this embodiment of
the invention, a prosthesis is formed consisting of an enlarged
midsection, and a pair of oppositely projecting distal and proximal
stem portions. The volar aspect of the midsection is machined to
exhibit an indent or transverse channel extending across its width,
to form the flexible hinge upon demineralization of the midsection.
The midsection, intended to act as the hinge, is demineralized, and
the mineralized extremities of the implant are retained in a
mineralized state for insertion of each end into the intramedullary
space of the bones adjacent to the joint which the implant
replaces. The mineralized extremities are machined to exhibit a
thread or a ratcheting tooth structure, such that upon insertion of
each end into the intramedullary space of the adjacent bones, the
end is fixed in place. Since the ends are made from bone, the
natural process of fusion between the implant and the bone into
which it is inserted occurs over several weeks, thus permanently
fixing the prosthesis into position and preventing any movement of
the ends of the implant. Implants according to this embodiment of
the invention may be used, for example, to replace
metacarpophalangeal joints, proximal interphalangeal joints and the
like. Accordingly, this invention represents a significant advance
in the art as it provides a natural alternative to currently
employed metallic, hydroxyapatite, silastic, silicone or like
elastomeric materials for joint arthroplasty.
[0042] In FIG. 8A, there is provided one diagrammatic
representation of an implant of a prosthetic joint according to
this invention and which may be prepared according to the concepts
central to the instant invention. The implant 800 has an enlarged
midsection 810 which is demineralized up to and including a portion
of the transition segment 820. On either side of the midsection 810
are mineralized projections 830 adapted for insertion into the
intramedullary canals of bones adjacent to the joint which the
implant 800 replaces. A groove or channel 850 is provided to act as
the hinge and to allow bending motion of the joint according to
principles described in U.S. Pat. No. 3,875,594, herein
incorporated by reference for this purpose. Optionally, the
projections 830 may exhibit an external feature designed to enhance
retention of the implant in the intramedullary spaces. In the
embodiment shown in FIG. 8A, this feature is shown as a tooth-like
serration which may be machined into an upper or lower aspect of
each projection 830 or which may project around the circumference
of the projections. Alternate external features which may aid in
retention of the implant include holes through which retention pins
may be inserted, grooves, ribbing and the like. The demineralized
midsection 810 permits the implant 800 sufficient flexibility to
allow that portion of the implant to act as a joint, while the
projections 830 fuse with the bone into which they are inserted to
form a permanent fixation. It will be appreciated that, as shown in
FIG. 8B, an implant 860 similar to that shown in FIG. 8A may be
implemented for inducing spinal fusion, whereby an intermediate
section 870 is demineralized while extensions thereof 880 are
retained in a mineralized state. In this embodiment, there is no
need for an enlarged internal segment of demineralized bone,
although there may be applications in which it is desirable for the
height H1 to be greater or smaller than the height H2. For example,
where the natural lordosis of the spinal segment into which the
implant 860 is to be inserted, the height H1 may preferably be
greater than the height H2. In addition, the upper surface 885, the
lower surface 886, or both may comprise features such as grooves,
pits, or projections which help retain the implant between
vertebrae when inserted into an intervertebral space.
[0043] Further applications to which the instant invention may be
applied include production of a segmentally demineralized anterior
longitudinal ligament (ALL) for stabilization of spinal motion
segments anteriorly after removal or ligation of an anterior
longitudinal ligament. An ALL produced according to the method of
this invention may be used to advantage to prevent expulsion of
interbody grafts, and is preferably affixed to the vertebral bodies
with screws, pins, staples or anchors of various types know in the
art or heretofore developed. As a result, lumbar extension is
reduced, thereby providing a more stable environment to promote
fusion. In FIG. 10, there is provided one embodiment 1000 of the
ALL according to this invention. The ALL 1000 is prepared from the
distal femur or other flat cortical surface, such as the proximal
humerus or tibia. A top portion 1010 and a bottom portion 1020 is
retained in a mineralized state, or is only partially
demineralized, or is surface demineralized to modify the
stress-fracture behavior of that portion of the implant. The top
portion 1010 and the bottom portion 1020 each have a series of
holes 1005 by means of which the ALL is affixed to a superior
vertebra V1 and an inferior vertebra V2. An intermediate section,
1030 is demineralized, to an extent sufficient to permit that
segment of the ALL to have a degree of flexibility. In this
fashion, while permitting a slight amount of motion, the ALL
substantially restricts motion at the vertebral segment spanned by
the ALL. Also shown in outline is a pair of interbody implants 1040
inserted between superior vertebra V1 and inferior vertebra V2,
spanned by the ALL, in order to induce fusion between V1 and V2. In
FIG. 10B, there is shown a further embodiment of the ALL of this
invention which is identical in all respects to the implant shown
in FIG. 10A, but wherein this embodiment has an enlarged upper
segment 1010' and lower segment 1020' for affixation to the
vertebrae V1 and V2. It will be appreciated that the precise shape
of the ALL is not critical. Furthermore, the ALL may span more than
two vertebrae.
[0044] In yet a further embodiment of the segmentally demineralized
implant of this invention, there is provided a spinal tension band,
STB. Typically, in spinal fusions, the motion segment adjacent to
the fused segment (the juxtaposed discs) have been found to rapidly
degrade. This degradation appears to be due to the hypermotion at
these levels, due to the decreased motion at the juxtaposed fused
segments. The STB of this invention assists in preventing this
degradation and can avoid the need for further surgery, by spanning
the fused segments and attaching to the juxtaposed vertebral body
at the spinous process thereof. The STB may be used in any region
of the spin, but is typically most useful for spanning fusions at
two, three or more levels. The STB of this invention replaces or
augments use of flexible stainless steel, titanium cables,
elastomeric or polymeric synthetic materials currently in use.
Accordingly, known techniques for attaching such devices to the
spinous processes may be used, or the STB may be affixed to
juxtaposed vertebral bodies in a fashion analogous to that
described above for the ALL. In FIG. 11, there is disclosed one
embodiment of the STB 1100 of this invention. As can be seen, the
STB 1100 is affixed to a superior vertebrae, VA, and an inferior
vertebra, VB, each of which are juxtaposed to a vertebrae V1 and
V2, which are being fused to each other by means of interbody
fusion devices IB1 and IB2. Intermediate portion 1110 of the STB
may be demineralized, while the top portion 1120 and bottom portion
1130 maybe retained in a mineralized or partially demineralized
state. Fixation means 1125 and 1135 are provided for fixation of
the STB to the juxtapose vertebrae VA and VB, respectively. Those
skilled in the art will appreciate that this embodiment of the
invention may be applied to any other anatomical structures to
minimize motion of such structures in relation to each other. For
example, the tension band of this invention may be utilized outside
of the spinal context, such as for repair of a split sternum in a
sternotomy.
[0045] In FIG. 12, there is shown a further embodiment 1200 of the
implant of this invention in the form of a sheet 1205 having a
plurality of perforations 1206 comprising mineralized 1210 and
demineralized 1220 segments. The perforated segmentally
demineralized sheet of this embodiment of the invention may be used
as a wrap or as a retention means for particulate material, gel
material and the like when deposited on, in or around a bone, for
example. Compositions which may be used in connection with this
embodiment of the invention include osteogenic bone paste and the
like.
[0046] In FIG. 13 there is shown a further embodiment 1300 of the
implant of this invention in the form of a screw made from cortical
bone, comprising at least a portion thereof which is demineralized
or partially demineralized. In this embodiment of the invention,
desirable physical characteristics, and in vivo remodeling
characteristics of such a device may be achieved by demineralizing
or partially demineralizing various segments of the screw. Thus,
for example, the point 1310 of the screw may be mineralized while
the thread 1320 or drive head 1330 may be partially demineralized,
to provide desirable surface characteristics, including but not
limited to greater capacity for in vivo remodeling or minimized
stress-fracture characteristics. In FIG. 14 A-C, there is shown a
further embodiment 1400 of the implant of this invention that is
particularly shaped to be used in spinal surgery. FIG. 14A shows a
side view of the implant 1400. The implant 1400 has an elongated
demineralized segment 1405 designed to be positioned in the
intervertebral space of the spine. Preferably the elongated segment
has a tapered end 1430 to resemble an intervertebral disc. Attached
and positioned transversely to the elongated demineralized segment
is a mineralized segment 1410. In a preferred embodiment, a damaged
or herniated disc is surgically removed from a patient and the
demineralized segment 1405 of the implant 1400 is inserted into the
space created by the excised disc. The mineralized segment can then
be affixed to the two adjacent (superior and inferior) vertebrae by
any suitable attachment means, e.g., screw, pin, staples, sutures,
etc., which can be made of inert materials such as metals or
polymers, or made of bone. To aid in the fixation of the implant
1400, the mineralized segment preferably has provided thereon one
or more holes 1420 to receive a screw or other fixation device.
FIG. 14B shows a rear view of the implant 1400 which illustrates
the holes 1420 as passing completely through the mineralized
segment. FIG. 14C shows a preferred embodiment of the implant which
comprises a demineralized portion 1425 surrounding the holes 1420.
This demineralized portion 1425 allows for flexibility and range of
motion of the implant 1400 when affixed. Based on this disclosure,
those skilled in the art will appreciate that the segment 1410 may
be mineralized, partially demineralized or completely
demineralized, while segment 1405 may be completely demineralized,
partially demineralized, or mineralized.
[0047] In FIG. 15, there is shown another embodiment 1500 of the
implant of the subject invention, which is a modified version of
implant 1400. Similar to implant 1400, implant 1500 comprises a
demineralized segment 1505, a mineralized segment 1510 transversely
attached to the demineralized segment 1505, holes 1520 disposed on
the mineralized segment 1510 for receiving an attachment means, and
a demineralized portion 1525 surrounding the holes 1520. The
demineralized segment 1505 of the implant 1500 is slightly curved
to accommodate possible irregularities in the patient's anatomy or
to provide different angles of approach for insertion of the
implant 1500. The implants 1500 and 1400 may be formed from a
unitary piece of bone or it may be assembled from different pieces
of bone and different portions of the implant may be partially or
completely demineralized.
[0048] In FIG. 16A-B, there is shown a further embodiment 1600 of
the implant of the subject invention that is comprised of a
multiple layers that is designed for use as a delivery vehicle,
wherein, preferably, one layer has infused therein a substance
having biological activity. The implant 1600 is preferably made of
a block of corticocancellous bone or cancellous bone having a
demineralized layer 1620 and a mineralized layer 1610. Delivery
vehicles such as sponges that are currently in use do not lead to
good bone formation, typically as a result of overlying muscle
tissue crushing and flexing the sponge. Besides disrupting the bone
rebuilding process (i.e., migration and attachment of bone
progenitor cells), the crushing of current sponge devices causes
the undesirable rapid release of osteogenic substances contained in
such sponges. The implant 1600 overcomes this problem by providing
a rigid, mineralized layer 1610 that protects the demineralized
layer 1620 from being crushed, thereby allowing a sustained release
of an additive infused therein. However, the demineralized layer
1620 possesses the ability to flex around internal structures. For
example, as shown in FIG. 16B, the implant 1600 is capable of
flexing around the transverse process of the spine 1630. In one
embodiment, the implant 1600 is produced by treating the cancellous
side of a corticocancellous plate with 0.5 N HC1 for approximately
one hour, thereby forming a demineralized layer. The resultant
implant can then be infused with a substance such as growth
factor(s), and the like. Accordingly, the implant 1600 provides a
delivery vehicle that is easy to produce and is made of a substance
that can be resorbed and remodeled by the body.
[0049] Additives can be infused into the implant 1600 by, for
example, soaking the demineralized portion in a solution containing
one or more additives. Examples of additives that can be infused
into implant 1600 include, but are not limited to, hydroxyapatite;
collagen and insoluble collagen derivatives, such as gelatin, and
soluble solids and/or liquids dissolved therein, e.g.,
antiviricides, particularly those effective against HIV and
hepatitis; antimicrobials and/or antibiotics such as erythromycin,
bacitracin, neomycin, penicillin, polymyxin B, tetracyclines,
viomycin, chloromycetin and streptomycins, cefazolin, ampicillin,
azactam, tobramycin, clindamycin and gentamycin, etc.; amino acids,
magainins, peptides, vitamins, inorganic elements, co-factors for
protein synthesis; hormones; endocrine tissue or tissue fragments;
synthesizers; enzymes such as collagenase, peptidases, oxidases,
etc.; polymer cell scaffolds with parenchymal cells; surface cell
antigen eliminators; angiogenic drugs and polymeric carriers
containing such drugs; collagen lattices; biocompatible surface
active agents; antigenic agents; cytoskeletal agents; cartilage
fragments, living cells such as chondrocytes, bone marrow cells,
mesenchymal stem cells, natural extracts, tissue transplants,
bioadhesives, growth factors, growth hormones such as somatotropin;
bone digestors; antitumor agents; fibronectin; cellular attractants
and attachment agents; immuno-suppressants; permeation enhancers,
e.g., fatty acid esters such as laureate, myristate and stearate
monoesters of polyethylene glycol, enamine derivatives, alpha-keto
aldehydes, etc.; nucleic acids; and, bioerodable polymers. In a
preferred embodiment, implant 1600 is infused with nucleic acids,
antibiotics, antiinflammatories, antineoplastics, or combinations
thereof.
[0050] Furthermore, growth factors can be infused into implant
1600, such as, for example, epidermal growth factor (EGF),
transforming growth factor-alpha (TGF-alpha), transforming growth
factor-beta (TGF-beta), human endothelial cell growth factor
(ECGF), granulocyte macrophage colony stimulating factor (GM-CSF),
bone morphogenetic protein (BMP), nerve growth factor (NGF),
vascular endothelial growth factor (VEGF), fibroblast growth factor
(FGF), insulin-like growth factor (IGF), platelet derived growth
factor (PDGF), cartilage derived morphogenetic protein (CDMP), or
combinations thereof.
[0051] FIG. 17 shows a further embodiment 1700 of the implant of
the subject invention which is comprised of demineralized bone
component 1710 and an external and/or internal support structure
component 1730. In a preferred embodiment, the implant 1700 has a
demineralized bone component that has inserted (e.g., woven)
therein a flexible support structure made of, for example, an inert
material such as titanium, titanium alloy, stainless steel,
stainless steel alloy, plastics, or combinations thereof. Other
suitable materials such as, but not limited to, resorbable or
nonresorbable polymers would be readily appreciated by those
skilled in the art. Preferably, the support structure 1730 is in
the shape of pins or wire and is malleable such that it can bend
and retain its bent shape. More preferably the support structure
spans at least one axis, or along two or more axes of the
demineralized component 1710. The implant 1700 may have pre-formed
holes 1720 which span along the x-axis, y-axis or both, or along a
diagonal axis of the demineralized component 1710 to accommodate
the structural component(s) 1730. The combination of the
demineralized bone component and the support structure provide an
implant that is flexible, malleable, and capable of retaining a
given shape. In an alternative embodiment, the support structure
1730 is made of cortical bone, wherein the cortical bone is fully
mineralized, or partially or fully demineralized. Naturally, using
mineralized cortical bone as the support structure 1730 will result
in the implant being more rigid.
[0052] FIG. 18 shows a further embodiment 1800 of the implant of
the subject invention. According to this embodiment, the implant
1800 comprises a demineralized plate 1810 that has positioned
thereon one or more mineralized areas 1820. Preferably, the
mineralized areas are positioned such that securing of the plate in
the implant area of a patient is optimized. Securing of the plate
comprises engaging an attachment means, such as a screw, pin,
staple, suture, etc., through the mineralized area and onto the
implant area. The mineralized area acts as a rigid substrate to
stabilize the contact between the attachment means and the implant
1800.
[0053] In FIG. 19(A-B), there is shown a further embodiment 1900 of
the subject invention that comprises a demineralized cortex region
1910 and a plurality of mineralized rows 1920 extending from the
demineralized cortex region 1910. The mineralized rows are aligned
along one axis of the implant 1900. This configuration allows for
flexibility of the implant in one axis and rigidity along the other
axis. For example, the embodiment as shown in FIG. 19 will bend on
itself on the y-axis but maintain rigidity on the x-axis. Depending
on the desired application, the dimensions of the implant 1900 can
vary. For example, as shown in FIG. 19B, dimension g preferably
ranges from 0.2 mm to 2 mm, dimension h preferably ranges from
about 0.5 mm to about 3.5 mm, dimension i preferably ranges from
about 0.2 mm to about 2 mm, and o preferably ranges from about 0.5
mm to about 5 mm
[0054] In FIG. 20, a further embodiment 2000 of the subject
invention is shown. This embodiment is preferably in the form of a
plate and comprises a demineralized cortex 2010 and a plurality of
mineralized projections 2020 extending from the demineralized
cortex 2010. In a preferred embodiment, the mineralized projections
2020 are aligned in rows spanning along both the x-axis and y-axis
of the implant 2000. This pattern gives the implant 2000
flexibility along multiple axes.
[0055] In FIG. 21, there is shown another embodiment 2100 of the
subject implant that is designed for repair or replacement of
ligaments and tendons. Implant 2100 is preferably made of partially
or fully demineralized bone (cortical, cortico-cancellous, or
cancellous). Implant 2100 comprises an elongated portion of bone
2110 that has a lumen 2120 formed within its interior, wherein the
lumen 2120 preferably but not necessarily comprises a channel that
runs completely through the elongated portion 2110. The lumen 2120
aids in the handling and attachment of the implant 2100 at the site
of need. Specifically, the lumen 2120 allows for the convenient
insertion of various surgical instruments to facilitate
manipulation of the implant 2100 both inside and outside the
patient during a surgical procedure. Further, depending on the
surgical procedure, the lumen 2120 allows for attachment of an end
of a damaged tendon, ligament, and/or bone, or some other body
part, by the simple insertion of the end of the tendon, ligament or
bone inside the lumen. The tendon or ligament can then be secured
to the implant 2100 by conventional methods such as, but not
limited to, suturing, pinning, tacking, and/or stapling.
Alternatively, the implant 2100 can be attached to one or more
bones, and/or muscle, to serve as a ligament or tendon. The implant
2100 can be attached to one or more bones through conventional
methods and need not utilize the lumen 2120 to facilitate
attachment, though use of the lumen 2100 for attachment is
preferred. Should there be a need, sutures can be passed through
the lumen, attached to the ligament or tendon, and then pulled back
into the lumen to help guide the ligament or tendon into the lumen.
Other advantages stemming from the provision of the lumen 2120 will
be apparent to those skilled in the art, in view of the teachings
herein.
[0056] In an even more preferred embodiment, the implant 2100 is
specifically implemented in ACL or other ligament reconstruction
surgeries. In the case of the ACL, the ACL and PCL cooperate,
together with other ligaments and soft tissue, to provide both
static and dynamic stability to the knee. Often, the anterior
cruciate ligament (i.e., the ACL) is ruptured or torn as a result
of, for example, a sports-related injury. Consequently, various
surgical procedures have been developed for reconstructing the ACL
so as to restore normal function to the knee. Some known methods
and techniques which have been used to repair and replace ACL
ruptures with grafts are discussed, for example, in Moore U.S. Pat.
No. 4,773,417, Goble U.S. Pat. No. 4,772,286 and an article by
Goble entitled "FLUORARTHROSCOPIC ALLOGRAFT ANTERIOR CRUCIATE
RECONSTRUCTION", Techniques Orthop. 1988 2(4):65-73. See also,
e.g., U.S. Pat. Nos. 6,056,752; 5,891,150; 5,941,883; 5,211,647;
and 5,320,626. It will further be appreciated that in this
embodiment of the invention, there need not be a main lumen. There
may be a plurality of lumens, into which various substances
mentioned herein may be infused.
[0057] In FIG. 22, there is shown a further aspect of this
invention wherein we have found that upon implantation of a
segmentally demineralized bone implant, cells contacted with the
demineralized portion of the implant infused that portion of the
bone, while the mineralized portions of the bone were infused to a
significantly lower extent. The implant 2200 is shown with suture
threading holes 2210 and 2220 for fixing the mineralized end 2230
to a desired location, while the demineralized segment 2240 is
available for use as a ligament, tendon or the like. This
particular implant was temporarily inserted into the knee joint of
a goat and then removed. The darker color of the segment 2240
clearly demonstrates the selective uptake of cellular and other
materials by the demineralized segment 2240 while the mineralized
end 2230 remains substantially white, due to the much lower
infiltration of cellular materials and other colored components.
This observation has implications for a number of applications.
Thus, for example, not meant to be limiting, the segmentally
demineralized bone implant is contacted with bone progenitor cells
prior to implantation. The demineralized portion of the bone
implant selectively takes up the bone progenitor cells, and upon
implantation, the infused portion of demineralized bone remodels
into autogenous bone more rapidly than the non-demineralized, less
infused portion of the bone implant. Alternatively, where the
demineralized portion of the bone is to act as a ligament or tendon
or cartilage, the appropriate cells, such as chondrocytes,
fibroblasts or the like are contacted with the demineralized
portion of the implant prior to implantation. As a result, upon
implantation, the demineralized, infused portion of the bone
implant remodels into the desired tissue form more rapidly than
does the mineralized portion of bone, which may remain in a rigid
form for anchoring of the implant to the recipient's bone. Those
skilled in the art will appreciate that this embodiment of the
invention may be applied to filly demineralized segments of bone,
by masking portions of the bone and allowing infiltration of
materials only into exposed portions of the demineralized bone.
Without wishing to be bound by any particular mechanistic
interpretation of the method and implant of this invention, it is
postulated that through removal of minerals from the bone matrix,
substantial internal porosity is induced, into which any or all of
the following materials are enabled to selectively infiltrate:
cells, including but not limited to mesenchymal stem cells (MSC's),
other cells, blood components, growth factors, including but not
limited to bone morphogenetic proteins, (BMPs), fibroblast growth
factors (FGFs), platelet derived growth factor (PDGF), cartilage
derived morphogenetic proteins (CDMPs), tissue derived growth
factors (TGFs), and the like, nucleic acids, especially nucleic
acids encoding such growth factors, proteins, peptides,
antibiotics, antineoplastics, anti-inflammatory compounds, and like
molecules. Such compounds, including antibiotics or the like may be
included in an implant where such compound is beneficial to a the
patient in amelioration of a condition under treatment. Thus, for
example, where a portion of bone is removed due to osteosarcoma,
infusion of the replacement bone implant with an antineoplastics
compound would be beneficial to prevent any potential metastasis
from diseased to new healthy tissue, and to treat any residual
tumor tissue through diffusion of the antineoplastics compound into
surrounding tissue. Those skilled in the art will appreciate that,
based on this disclosure, any other desirable material, even though
not specifically disclosed or suggested herein, may be selectively
infused into a bone implant through practicing the methods of this
invention as disclosed herein.
[0058] Having now generally described various embodiments of this
invention, the following examples are provided by way of further
exemplification of this invention. It should be recognized that the
invention disclosed and claimed herein is not to be limited to the
specifics provided in these examples, but is to be determined by
the claims appended hereto:
EXAMPLE 1
Machining of the Implant of this Invention
[0059] The starting bone stock was chosen such that a piece of bone
consisting substantially of cortical bone was used to machine the
implant of this invention. Implants from the linea aspera of the
femur or an anterior aspect of the tibia were used for this
purpose, but other cortical sources of bone would be acceptable.
The desired bone segment was removed with a bone saw or a
water-cooled diamond core cutter, and trimmed to fit in a lathe for
machining of desired external features. The bone was first machined
to a known diameter and length. The ends were then machined to
exhibit an internal thread, an external thread, or to have one
machined end while the other end of the implant was drilled to
exhibit one to several holes. The internal segment destined for
demineralization was then either retained in a cylindrical form or
machined in a milling machine or a grinder, to exhibit a flat
internal segment, or another desired shape, between the threaded
ends or the fixation ends.
EXAMPLE 2
Segmental Demineralization of Machined Bone Grafts
[0060] 1. Large Cylindrical Ligament Repair Grafts:
[0061] Demineralization of a machined large cylindrical ligament
repair graft was completed in three days using approximately 40 mL
of 0.75 M-1.0 M hydrochloric acid solution. The implant was exposed
to fresh solution at least once per day. In order to produce a
gradual transition from a fully mineralized end to a fully
demineralized segment, the point of contact of the HC1 solution
with the implant was varied over the duration of the
demineralization process.
[0062] 2. Small Cylindrical Ligament Repair Grafts:
[0063] Demineralization of a machined small cylindrical ligament
repair graft was completed in two days using approximately 40 mL of
0.75 M-1.0 M hydrochloric acid solution. The implant was exposed to
fresh solution at least once per day. In order to produce a gradual
transition from a fully mineralized end to a fully demineralized
segment, the point of contact of the HC1 solution with the implant
was varied over the duration of the demineralization process.
[0064] 3. Flat Ligament or Tendon Repair Grafts:
[0065] Demineralization of a machined ligament or tendon repair
graft wherein an internal segment of the graft was machined flat,
was completed in twenty-four hours using approximately 40 mL of
0.75 M-1.0 M hydrochloric acid solution. The implant was exposed to
fresh solution at least once per day. In order to produce a gradual
transition from a fully mineralized end to a fully demineralized
segment, the point of contact of the HC1 solution with the implant
was varied over the duration of the demineralization process.
[0066] 4. Double Flat Ligament Repair Grafts Having Two Rigid
Ends:
[0067] Demineralization of a machined, flat ligament repair graft
was completed in twenty-four hours using approximately 40 mL of
0.75 M-1.0 M hydrochloric acid solution. The implant was exposed to
fresh solution at least once per day. In order to produce a gradual
transition from a fully mineralized end to a fully demineralized
segment, the point of contact of the HC1 solution with the implant
was varied over the duration of the demineralization process. In
order to protect both rigid ends of the implant, one bearing a
thread and the other being a fixation block, the implant was
exposed to the acid solution only in the middle segment by keeping
the threaded end of the implant above the meniscus of the acid, and
the fixation block end of the implant was inserted into a bored-out
stopper, which also acted as a plug at the bottom of the acid
container, into which a hole adequate to receive the implant
bearing stopper had been drilled.
[0068] In view of the foregoing disclosure and examples, in which
various embodiments of the implant of this invention are disclosed
and described, including the best mode, the following claims are
provided to define the scope of this invention. Those skilled in
the art will recognize that various modifications on the specifics
of the invention disclosed herein come within the scope of the
appended claims.
EXAMPLE 3
ALL, STB, Craniomaxillofacial and Bone-Wrap Implants
[0069] Following the procedures outlined in this disclosure, a flat
cortical segment of bone is partially demineralized to form an ALL
replacement or an STB, for stabilization of portions of the spine
undergoing fusion. The ALL is affixed to two adjacent vertebrae
undergoing fusion, while the STB is affixed to vertebrae juxtaposed
to vertebrae undergoing fusion. The mineralized portion of the ALL
and STB are utilized to affix the implants to the vertebrae by
means of cortical bone screws, metallic pins or by hooking
demineralized portions of the ALL or STB over vertebral processes.
Craniomaxillofacial implantation of a pizza shaped implant such as
that shown in FIG. 9 is achieved by resecting a portion of the skin
and musculature above a craniomaxillofacial defect and laying the
implant over the defect in a contoured fashion. The implant is
maintained in place by repair of the superior skin and musculature.
In the case of the bone-wrap, a sheet of cortical bone is
segmentally masked such that adjacent liner segments of alternating
mineralized and demineralized bone are produced upon contact of the
masked bone to demineralizing agents such as acetic acid,
hydrochloric acid, chelating agents, and the like. The bone-wrap is
wrapped around a segment of fractured bone to provide support and
to contain added osteogenic compositions to maximize repair of the
fractured bone.
EXAMPLE 4
Selective Uptake of Materials by Segmentally Demineralized Bone
Implants
[0070] In accordance with one aspect of the present invention, any
implant disclosed herein or a variant thereof may be modified by
selective infusion into the demineralized portion of the implant of
any desirable material, including but not limited to: cells,
including but not limited to mesenchymal stem cells (MSC's), other
cells, osteoblasts, osteoclasts, chondrocytes, fibroblasts,
chondrogenic stem cells, hematopoietic stem cells, blood
components, growth factors, including but not limited to bone
morphogenetic proteins, (BMPs), fibroblast growth factors (FGFs),
platelet derived growth factor (PDGF), cartilage derived
morphogenetic proteins (CDMPs), tissue derived growth factors
(TGFs), and the like, nucleic acids, especially nucleic acids
encoding such growth factors, proteins, peptides, antibiotics,
antineoplastics, anti-inflammatory compounds, and like molecules.
Those skilled in the art will appreciate that, based on this
disclosure, any other desirable material, even though not
specifically disclosed or suggested herein, may be selectively
infused into a bone implant through practicing the methods of this
invention as disclosed herein.
[0071] In one particular example, a bone implant was machined in
the form of a ligament with a mineralized portion of the implant
bearing holes for suture passage therethrough. A second portion of
the implant was demineralized, and the entire segmentally
demineralized bone implant was implanted into an animal model to
test for strength of the implant used as a ligament replacement. It
was noted that after presence in the biological system, the
demineralized portion of the implant had a much darker color than
the portion of the implant that was left in a mineralized state.
This observation leads to the conclusion that the demineralized
portion of the implant is taking up materials with which it is
contacted much more efficiently than the mineralized portion of the
implant. Accordingly, various implants are prepared with different
degrees of demineralization, and such implants are contacted with
various materials including, but not limited to those described
above. As a result, a wide variety of properties may be conferred
on the implants thus treated to achieve desired biological
functions, from the formation of connective tissues, bone,
cartilage, and the like. Use of masking procedures facilitates the
production of implants with complex patterns of material uptake, as
needed.
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