U.S. patent application number 14/447085 was filed with the patent office on 2015-02-26 for method for 3-d printing a custom bone graft.
The applicant listed for this patent is Arthur Greyf. Invention is credited to Arthur Greyf.
Application Number | 20150054195 14/447085 |
Document ID | / |
Family ID | 52479651 |
Filed Date | 2015-02-26 |
United States Patent
Application |
20150054195 |
Kind Code |
A1 |
Greyf; Arthur |
February 26, 2015 |
Method for 3-D Printing a Custom Bone Graft
Abstract
A method for producing bone grafts using 3-D printing is
employed using a 3-D image of a graft location to produce a 3-D
model of the graft. This is printed using a 3-D printer and an ink
that produces a porous, biocompatible, biodegradable material that
is conducive to osteoinduction. This is porous poly methyl
methacrylate (PMMA) made osteoinductive by demineralized bone
(DMB). The ink is provided as a precursor powder and liquid. The
powder contains DMB, sucrose crystals and a polymerization
initiator. The liquid contains methyl methacrylate (MMA). Optional
compounds include antibiotics, radio-pacifiers, and compounds to
increase biodegradability. Once mixed, the MMA polymerizes to PMMA.
The ingredients are proportioned so that the ink is delivered
through a 10 gauge print nozzle for about 10 minutes per batch.
Once the graft is placed, natural bone gradually replaces the
graft.
Inventors: |
Greyf; Arthur; (Livingston,
NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Greyf; Arthur |
Livingston |
NJ |
US |
|
|
Family ID: |
52479651 |
Appl. No.: |
14/447085 |
Filed: |
July 30, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61901043 |
Nov 7, 2013 |
|
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|
61867755 |
Aug 20, 2013 |
|
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Current U.S.
Class: |
264/250 ;
264/308 |
Current CPC
Class: |
B29C 48/02 20190201;
A61F 2310/00359 20130101; G05B 2219/49023 20130101; A61F 2240/002
20130101; A61F 2002/3092 20130101; A61F 2002/2853 20130101; B29L
2031/7532 20130101; B29K 2029/04 20130101; B29K 2067/046 20130101;
B29K 2995/0056 20130101; B29K 2105/0005 20130101; B29K 2105/0035
20130101; A61F 2002/30952 20130101; B29K 2033/12 20130101; A61F
2/28 20130101; A61F 2002/30962 20130101; A61F 2310/00353 20130101;
A61F 2/30942 20130101; B29C 64/165 20170801; B29K 2105/0011
20130101; B29K 2105/04 20130101; A61F 2002/30948 20130101; G05B
2219/45168 20130101; A61F 2002/30957 20130101; A61F 2002/2825
20130101; G06F 30/20 20200101; B33Y 10/00 20141201; B29K 2039/06
20130101; B29K 2105/0088 20130101; B29K 2995/006 20130101; B29K
2001/12 20130101; B29K 2105/0014 20130101; A61F 2002/30971
20130101; B33Y 70/00 20141201; B29C 48/266 20190201; G05B 19/4099
20130101 |
Class at
Publication: |
264/250 ;
264/308 |
International
Class: |
B29C 67/00 20060101
B29C067/00; A61F 2/28 20060101 A61F002/28 |
Claims
1. A method for producing a custom bone graft, comprising:
obtaining a 3-D image of an intended graft location; creating a 3-D
digital model of said custom bone graft using said 3-D image; and
creating, using a 3-D printer said custom bone graft using an ink
that dries or reacts to form a porous, biodegradable, biocompatible
material that is conducive to osteoinduction and has a load bearing
strength comparable to bone.
2. The method of claim 1 wherein said porous, biodegradable,
biocompatible material comprises collagen and bone morphogenetic
proteins (BMP).
3. The method of claim 1 wherein said porous, biodegradable,
biocompatible material comprises porous Poly Methyl Methacrylate
(PMMA) and demineralized allograft bone matrix (DMB).
4. The method of claim 3 wherein said ink comprises Methyl
Methacrylate (MMA), demineralized allograft bone matrix (DMB),
sucrose crystals and a radical polymerization initiator.
5. The method of claim 4 wherein said radical polymerization
initiator comprises benzoyl peroxide.
6. The method of claim 4 wherein said ink further comprises an
antibiotic.
7. The method of claim 6 wherein said antibiotic consists of one of
amoxicillin, doxycycline, gentamicin and clindamycin, or some
combination thereof.
8. The method of claim 4 wherein said ink further comprises a
radio-pacifier.
9. The method of claim 8 wherein said radio-pacifier consists of
one of zirconium dioxide (ZrO.sub.2) and barium sulphate
(BaSO.sub.4) or some combination thereof.
10. The method of claim 4 wherein said ink further comprises a
compound to increase the biodegradability of said ink.
11. The method of claim 10 wherein said compound to increase the
biodegradability of said ink consists of one of cellulose acetate
(CA) and cellulose acetate phthalate (CAP) or a combination
thereof.
12. The method of claim 3 wherein said ink is comprised of a
precursor powder and a precursor liquid, and wherein said powder is
comprised of demineralized allograft bone matrix (DMB), sucrose
crystals and a radical polymerization initiator, and said liquid
comprises methyl methacrylate (MMA), and when said precursor powder
and said precursor liquid are mixed prior to form said ink in said
3-D printer.
13. The method of claim 1 wherein said 3-D image is obtained using
one or more X-ray images.
14. The method of claim 1 wherein said 3-D digital model further
comprises using a standard model of a body part.
15. The method of claim 1 further including a semipermeable,
resorbable membrane printed on top of said custom bone graft using
a second ink.
16. The method of claim 15 wherein said second ink comprises
poly-vinyl alcohol (PVA) and poly-vinyl pyrrolidone (PVP).
17. The method of claim 1 wherein said 3-D image is obtained using
a Cone beam imaging device or a cat-scan device.
18. The method of claim 1 wherein said porous, biodegradable,
biocompatible material comprises a resorbable cement, cellulose, a
synthetic bone morphogenetic protein, and one of hydroxyapatite,
allograft particulate bone, xenograft particulate bone, or a
combination thereof.
19. The method of claim 18 wherein said resorbable cement comprises
porous Poly Methyl Methacrylate (PMMA), and said synthetic bone
morphogenetic protein comprises recombinant human Bone
Morphogenetic Protein-2 (rhBMP-2).
20. A method for producing a custom bone graft, comprising:
obtaining a 3-D image of an intended graft location; creating a 3-D
digital model of said custom bone graft using said 3-D image;
generating a 3-D digital graft model 310 of a graft negative mold
305 for said custom bone graft using said 3-D digital model; and
creating, using said 3-D digital mold and a porous, biodegradable,
biocompatible material that is conducive to osteoinduction and has
a load bearing strength comparable to bone, to produce said custom
bone graft.
21. The method of claim 20 wherein generating a 3-D digital mold of
a negative mold for said custom bone graft further comprises using
a 3-D printer.
22. The method of claim 20 wherein said porous, biodegradable,
biocompatible material comprises collagen and bone morphogenetic
proteins (BMP).
23. The method of claim 20 wherein said porous, biodegradable,
biocompatible material comprises porous Poly Methyl Methacrylate
(PMMA) and demineralized allograft bone matrix (DMB).
Description
CLAIM OF PRIORITY
[0001] This application claims priority to U.S. Provisional Patent
Application 61/901,043 filed on Nov. 7, 2013 and to U.S.
Provisional Patent Application 61/867,755 filed on Aug. 20, 2013
the entire contents of both of which are hereby fully incorporated
by reference.
FIELD OF THE INVENTION
[0002] The invention relates to producing a custom bone graft, and
more particularly to methods of producing custom bone grafts using
3-D printing and/or CNC machining, or a combination thereof.
BACKGROUND OF THE INVENTION
[0003] Bone grafting is possible because bone tissue, unlike most
other tissues, has the ability to regenerate completely if provided
the right environment, including a space into which to grow, or a
matrix to grow on. As native bone grows, it replaces the graft
material, so that over time, the graft is replaced by a fully
integrated region of new bone.
[0004] Bone regeneration occurs through osteoinduction, a process
in which connective tissue is converted into bone by an appropriate
stimulus. Osteoinduction allows bone formation to be induced even
at non-skeletal sites and is initiated by bone morphogenetic
proteins (BMP).
[0005] The ideal bone graft material would be a strong, porous
biocompatible material infused with BMP that did not cause
inflammation and would ultimately be reabsorbed into the body as it
is replaced by natural bone.
[0006] Bone is composed of 50 to 70% inorganic mineral, 20 to 40%
organic collagen matrix, 5 to 10% water, and <3% lipids. The
inorganic mineral content of bone is mostly hydroxyapatite
[Ca.sub.10(PO.sub.4)6(OH).sub.2]. The inorganic mineral provides
the mechanical strength and rigidity, whereas the organic collagen
matrix provides elasticity and flexibility.
[0007] Demineralized bone matrix (DBM) is allograft bone, i.e.,
bone from other humans, that has had the inorganic, mineral
material removed, leaving behind the organic collagen matrix and
the BMPs that induce osteoinduction. DBM is conducive to
osteoinduction, but lacks the load bearing strength. It is
typically used with a 2-4% hyaluronate carrier as a paste or putty
to fill a space needing bone, and allows real bone to grow into it
within weeks to months.
[0008] The present invention provides a system and method of
producing custom bone grafts that are made of a porous,
biocompatible material infused with BMPs that can be used as ink in
a 3-D printer to produce bone grafts of any desired shape.
DESCRIPTION OF RELATED ART
[0009] U.S. Patent Application 2011/0151400 published by A.
Boiangiu et al. on Jun. 23, 2011 entitled "Dental Bone Implant,
Methods for Implanting the Dental Bone Implant and Methods and
Systems for Manufacturing Dental Bone Implants" that describes a
dental bone implant having a first fitted bone graft sized and
shaped to fit tightly to a buccal surface of a periodontal alveolar
bone around at least one tooth and to reconstruct at least a
portion of one or more periodontal bone defect and a second fitted
bone graft sized and shaped to fit tightly to a lingual/palatal
surface of a periodontal alveolar bone around at least one tooth
and to reconstruct at least an additional portion of at least one
periodontal bone defect. The portion and the other portion
complementary cover the one or more periodontal bone defects.
[0010] U.S. Patent Application 2004/0120781 published by S. Luca et
al. on Jun. 24, 2004 entitled "Customized instruments and parts for
medical-dental applications and method and blank for on-site
machining of same" that describes a customized prosthesis, or
instrument, for medical/dental applications which replicates the
desired bone-graft, tooth, or tool, being replaced. The dimensions
of the prosthesis, or instrument, are determined by mathematically
interpolating key-points that characterize a specific part. A
computer controlled machine then cuts the desired part out of a
pre-fabricated blank, directly at the site of operation. Methods of
the invention relate to selecting the type of part being replaced,
identifying and measuring the coordinates of key-points for that
part, and initializing the automated machining process. Also,
special supporting devices that include pre-fabricated features
common between certain parts are used in order to facilitate the
machining process. The identification of key-points is done by
comparing a schematic drawing of the type of part being replaced to
the actual part. A grid is then used to measure the coordinates for
those key-points.
[0011] U.S. Pat. No. 6,671,539 issued to Gateno et al. on Dec. 30,
2003 entitled "Method and apparatus for fabricating orthogenetic
surgical splints" that describes a method of forming a surgical
splint to receive a patient's dentition and thereby align the upper
jaw and the lower jaw during surgery includes generating a CT
computer model of bone structure, generating a digital dental
computer model of the patient's dentition, and then combining the
CT computer model and the digital dental computer model to form a
composite computer model. The composite computer model may be
displayed, and at least one of the upper jaw and lower jaw
repositioned relative to the patient's skull and the composite
computer model to form a planned position computer model. Using
this desired position computer model, a computer model surgical
splint of the patient's dentition may be formed, which is then
input into a fabrication machine to form a surgical splint. The
method also includes forming and displaying the composite computer
model. A workstation includes a CT machine, a digital scanner, a
computer, an input command mechanism, a display, and a fabricating
machine.
[0012] U.S. Pat. No. 8,021,154 issued to Holzner et al. on Sep. 20,
2011 entitled "Method for manufacturing dental prostheses, method
for creating a data record and computer-readable medium" that
describes a method for manufacturing one or several dental
prostheses, comprising the steps of: performing a rapid prototyping
method for manufacturing one or several dental prostheses and
subsequent working, such as reworking, of the one or several dental
prostheses with a machining method, such as a milling method. In
addition, a method for creating a data record which can be used for
a rapid prototyping method for manufacturing a dental prosthesis
wherein an end data record is obtained from a starting data record,
so that in at least one area of a dental prosthesis manufactured
with the end data record excess material is provided, compared to a
dental prosthesis manufactured with the starting data record.
[0013] Various implements are known in the art, but fail to address
all of the problems solved by the invention described herein. One
embodiment of this invention is illustrated in the accompanying
drawings and will be described in more detail herein below.
SUMMARY OF THE INVENTION
[0014] The present invention describes systems and methods for
producing a custom bone graft. In a preferred embodiment, a 3-D
image of an intended graft location may be obtained. This may be
achieved by a number of methods, some of which may be discussed in
further detail later. Use may, for instance, be made of 3-D image
construction techniques such as, but not limited to, obtaining
multiple 2-D X-ray images at different orientations, and using
computational techniques to convert these into a 3-D image, using a
Cone beam imaging device or a cat-scan device, or some combination
thereof.
[0015] This 3-D image of the graft location may then be converted
into a 3-D digital image of the custom bone graft.
[0016] The custom bone graft may be printed directly using a
modified 3-D printer and an ink that transforms into a suitable
porous, biocompatible, biodegradable material that is conducive to
osteoinduction and has a load bearing strength comparable to
bone.
[0017] The custom bone graft may also or instead be made by using a
3-D printer to print a negative form or mold, and the mold may then
be used to produce the custom bone graft. In such a process, in a
preferred embodiment, the mold may be filled with a mixture of, for
instance, Calcium Sulfate hemihydrate, aka Plaster of Paris,
demineralized freeze dried bone (DFDB), or freeze dried bone (FDB),
Bone Morphogenetic Proteins (BMP) and an antibiotic such as, but
not limited to, Doxycycline.
[0018] In a preferred embodiment, the porous, biocompatible
material may be porous Poly Methyl Methacrylate (PMMA) and
demineralized allograft bone matrix (DMB). The ink for this
material may, for instance, be provided as a precursor powder, and
a precursor liquid. The precursor powder may, for instance, include
demineralized allograft bone matrix (DMB), sucrose crystals and a
radical polymerization initiator. The precursor liquid may, for
instance, include Methyl Methacrylate (MMA) as well as one or more
antibiotics and one or more radio-pacifiers, i.e., compounds that
make the graft more radio opaque, or radio dense, so that it may be
more visible on X-ray images.
[0019] In a preferred embodiment, the radical polymerization
initiator may be benzoyl peroxide, the antibiotic may be gentamicin
and the radio-pacifier may be barium sulphate.
[0020] The precursor liquid and powder may be mixed in small
batches to produce the ink just before printing. Once the
precursors are mixed the MMA may start to polymerize to PMMA. The
viscosity of the liquid will increase with time, but suitably
proportioned, the ink may be delivered through a 10-14 gauge needle
or print nozzle for about 10 to 20 minutes. This may provide a dot
size of about 2 mm in diameter, which may be the resolution of the
finest detail of the custom bone graft.
[0021] The sucrose crystals provide the porosity to the structure
when they are dissolved out in post print processing.
[0022] The structure printed by the ink may also be made
biodegradable by the inclusion of cellulose acetate (CA) or
cellulose acetate phthalate (CAP), or a combination thereof. The
biodegradability may allow the porous PMMA structure to be replaced
by natural bone over time.
[0023] Therefore, the present invention succeeds in conferring the
following, and others not mentioned, desirable and useful benefits
and objectives.
[0024] It is an object of the present invention to provide custom
bone grafts suitable for use in disciplines such as, but not
limited to, Orthopedics, Plastic Surgery, ENT and Dentistry.
[0025] It is a further object of the present invention to be of use
in procedures, including plastic surgery procedures, such as, but
not limited to, cleft palate surgical repair, facial and non-facial
post trauma or tumor removal reconstruction.
[0026] It is an object of the present invention to provide a method
of producing custom bone grafts at a reasonable price.
[0027] It is a further object of the present invention to provide
bone grafts that may be an intimate fit to the graft site, as this
may increase the chances of bone graft maturation and healing, and
because intimate contact is one predictor of a successful
surgery.
[0028] It is another object of the present invention to provide a
method of producing a custom bone graft using equipment that may be
located at a surgeon, or plastic surgeon's, site or office.
[0029] It is an object of the present invention to provide suitable
ink for use in suitably modified 3-D printers.
[0030] It is a further object of the present invention to design
and fabricate bone grafts to add lost tissue or tissue that was
never developed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] FIG. 1 shows a preferred embodiment of a method for
producing a custom bone graft.
[0032] FIG. 2 shows a magnified section of the mineral structure of
bone.
[0033] FIG. 3 shows a magnified section of a demineralized
allograft bone matrix (DMB).
[0034] FIG. 4 shows a magnified section of a porous, biocompatible
material suitable for use as a bone graft.
[0035] FIG. 5 shows a magnified section of an intermediate stage in
producing porous Poly Methyl Methacrylate (PMMA).
[0036] FIG. 6 shows a sematic layout of the ink mixing and print
nozzle of a preferred embodiment of the present invention.
[0037] FIG. 7 shows a sematic flow diagram of representative steps
of a preferred embodiment of the present invention.
[0038] FIG. 8 shows a cone-beam scan of a patient used by computer
software to produce an image of a bone defect.
[0039] FIG. 9 shows a sectional view of a 3-D reconstruction of an
imaged defect.
[0040] FIG. 10 shows a sectional view of a computer generated 3-D
positive image of a required graft.
[0041] FIG. 11 shows a sectional view of a negative mold of a
required graft.
[0042] FIG. 12 shows a sectional view of a negative mold being used
to produce a required graft.
[0043] FIG. 13 shows a sectional view of a graft being placed
during surgery.
[0044] FIG. 14 A shows a required complex long bone graft.
[0045] FIG. 14 B shows a negative mold for a portion of the
required complex long bone graft.
[0046] FIG. 14 C shows a negative mold being used to produce a
portion of the required complex long bone graft.
[0047] FIG. 14 D shows a negative mold being used to produce a
portion of the required complex long bone graft.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0048] The preferred embodiments of the present invention will now
be described with reference to the drawings. Identical elements in
the various figures are identified with the same reference
numerals.
[0049] Various embodiments of the present invention are described
in detail. Such embodiments are provided by way of explanation of
the present invention, which is not intended to be limited thereto.
In fact, those of ordinary skill in the art may appreciate upon
reading the present specification and viewing the present drawings
that various modifications and variations can be made thereto.
[0050] FIG. 1 shows a preferred embodiment of a method for
producing a custom bone graft. An X-ray imaging machine 155 may be
used to take one or more images of a region of a patent where a
custom bone graft 120 may be needed. These may then be assembled
into a 3-D image 105 of the region requiring a custom bone graft
120. A suitably programmed digital processor 240 may take the 3-D
image 105 and transform it into a 3-D model of the region requiring
the custom bone graft 120. This 3-D model may then be used to
generate a 3-D model of the required custom bone graft 120. This
3-D model of the required custom bone graft 120 may then be used by
a software module operative on the digital processor 240 to
generate instructions for a 3-D printer 115. These instructions
may, for instance, take the form of a 3-D digital model 110 made up
of a series of layers 245. These layers of a 3-D digital model 245
may, for instance, be sized to the resolution of the 3-D printer
115 that may be used to generate the custom bone graft 120. A 3-D
printer 115 may then be used to produce the custom bone graft 120
layer by layer using an appropriate ink, or series of inks.
[0051] In a preferred embodiment, the X-ray imaging machine 155 may
be a Cone Beam 3 D camera such as, but not limited to, the model GX
DP-700 supplied by Gendex Dental Systems of Hatfield, Pa. In other
embodiments, other imaging devices may be used such as, but not
limited to, other computer aided tomography devices, cat-scan
devices, 3-D laser cameras or a combination thereof.
[0052] FIG. 2 shows a magnified section of the mineral structure of
bone. Mammalian bone may be composed of a bone mineral 215 having a
lattice or matrix of voids 220. Bone may typically be composed of
50 to 70% inorganic mineral, 20 to 40% organic collagen matrix, 5
to 10% water, and <3% lipids. The organic collagen, water,
lipids and blood vessels are typically contained within the voids.
The inorganic mineral content of bone is mostly hydroxyapatite
[Ca.sub.10(PO.sub.4).sub.6(OH).sub.2]. The inorganic mineral
provides the mechanical strength and rigidity, whereas the organic
collagen matrix provides elasticity and flexibility.
[0053] FIG. 3 shows a magnified section of a demineralized
allograft bone matrix (DMB). The demineralized allograft bone
matrix (DMB) 145 may be made up of collagen 130, typically formed
into a matrix structure, and bone morphogenetic proteins (BMP) 135.
Bone morphogenetic proteins (BMPs) are a group of growth factors
also known as cytokines and as metabolomes. They were originally
discovered through their ability to induce the formation of bone
and cartilage, and are now considered to constitute a pivotal group
of morphogenetic signals that may orchestrate tissue architecture
throughout the body. Although bone morphogenetic proteins (BMP) 135
may be manufactured by genetic engineering, demineralized allograft
bone matrix (DMB) 145 is a favored source, and may be used in a
paste or putty to facilitate bone regeneration. Demineralized
allograft bone matrix (DMB) 145, i.e., allograft bone that has had
inorganic minerals removed, may expose more bone morphogenetic
proteins (BMP) 135 and therefore facilitate faster growth of
natural bone into the paste or putty. Demineralized allograft bone
matrix (DMB) 145 does not, however, have the strength of natural
bone. Allograft bone is human bone, typically taken from cadavers
and bone banks.
[0054] Demineralized allograft bone (DMB) 145 may be obtained from,
for instance, MAXXEUS Inc., of Kettering, Ohio who sells it under
the brand name MAXXEUS.TM. DBM PUTTY.
[0055] FIG. 4 shows a magnified section of a porous, biocompatible
material suitable for use as a bone graft. The porous,
biocompatible material 125 may, for instance, be made up of a
biocompatible, porous structural support 250 made conducive to
osteoinduction by the presence of bone morphogenetic proteins (BMP)
135.
[0056] In a preferred embodiment, the biocompatible, porous
structural support 250 may, for instance, be porous Poly Methyl
Methacrylate (PMMA) 140 and the bone morphogenetic proteins (BMP)
135 may, for instance, be demineralized allograft bone matrix (DBM)
145. The bone morphogenetic proteins (BMP) 135 may also, or
instead, be a synthetically produced compound such as, but not
limited to, recombinant human Bone Morphogenetic Protein-2
(rhBMP-2) as provided by, for instance, Medtronic Inc. of
Minneapolis, Minn. in their INFUSE Bone Graft material.
[0057] Poly Methyl Methacrylate (PMMA) 140 is a synthetic polymer
of methyl methacrylate, whose biocompatibility was, apparently,
discovered by accident during WWII when RAF pilots suffered eye
injuries from the destruction of their side widows. Hawker
Hurricane pilots, whose windows were made of glass, suffered severe
rejection/infection in the vicinity of the glass splinters in their
eyes, while Spitfire pilots, whose side windows were made of PMMA
suffered no rejection/infection in the vicinity of the PMMA
splinters. This good degree of compatibility with human tissue has
been exploited by using PMMA for intraocular eye lenses that
replace cataract damaged lenses, and in orthopedic surgery. In
orthopedic surgery it is used as a grout, or bone cement, to
stabilize join implants. PMMA bone cement such as, but not limited
to, SIMPLEX P.TM. BONE CEMENT sold by the Stryker Corporation of
Kalamazoo, Mich. is typically supplied as a powder and a liquid.
The ingredients of Stryker's SIMPLEX P.TM. BONECEMENT are reported
to be 75% methyl methacrylate; 15% polymethylmethacrylate (PMMA);
10% Barium Sulfate for radio-opaqueness, and an undisclosed
quantity of benzoyl peroxide to initiate the radical induced
polymerization of the MMA to PMMA. The amount of the radical
polymerization initiator, benzoyl peroxide, may be crucial for
determining the mixing, handling, and setting characteristics of
the bone cement.
[0058] In orthopedic use, the powder and liquid precursors are
mixed about 10 minutes before being used. Mixing the powder and
liquid initiates the polymerization, which may take up to several
hours to complete. They are either applied as putty, or delivered
to the required site by means of needles that range in size from 10
to 14 gauges, i.e., in the vicinity of 2 mm internal bore
needles.
[0059] FIG. 5 shows a magnified section of an intermediate stage in
producing porous poly methyl methacrylate (PMMA).
[0060] The porous Poly Methyl Methacrylate (PMMA) 140 may be
produced by including sucrose crystals 170 of the appropriate size
in the MMA being polymerized. After the MMA is fully polymerized
from its liquid form to solid form, the sucrose crystals 170 may be
dissolved out, leaving behind a porous PMMA structure.
[0061] This method of producing a porous PMMA structure was
developed in order to overcome some shortcomings of existing PMMA
bone cement, as reported by A. Rijke et al in an article entitled
"Porous Acrylic Cement" published in J Biomed Mater Res. 1977 May;
11(3):373-94, the contents of which are hereby incorporated by
reference.
[0062] Shortcomings of PMMA bone cement include that it heats up to
82.5.degree. C. (160.5.degree. F.) while setting. This is high
enough to cause thermal necrosis of neighboring tissue, or any
biomaterial such as, but not limited to, collagen and bone
morphogenetic proteins (BMP) that may be found in demineralized
allograft bone matrix (DMB).
[0063] By modifying the cement composition through the addition of
soluble, nontoxic filler such as sucrose or tri-calcium phosphate
which does not impair the workability of the material during
surgery, a significant improvement in the performance of the cement
can be achieved. Because the filler replaces part of the acrylic
components, less heat is generated during curing while the filler
itself acts as a heat sink.
[0064] Porous cement may be obtained provided that a critical
minimum percentage loading of the filler is exceeded so that the
filler crystals will make physical contact with each other. The
value of this percentage depends on both crystal modification and
size. With crystals in the 125-175 micron range, the critical
minimum percentage may be in the range of 20-28 wt. % loading.
Above 30%, the interconnecting pore size increases and may allow
good tissue ingrowth into the pores. The introduction of filler and
pores may cause a drop in strength, but the tensile strength of
modified cement containing up to 40% pores and sucrose lies between
0.7 and 1.5 kg/mm.sup.2', which is in the same range as that of
bone.
[0065] Poly methyl methacrylate (PMMA) may be made biodegradable by
the addition of cellulose acetate (CA) 255 or cellulose acetate
phthalate (CAP) 260, as described in, for instance, an article by
D. Batt et al. entitled "Biodegradability of PMMA Blends with Some
Cellulose Derivatives", published in Journal of Polymers and the
Environment, October 2006, Volume 14, Issue 4, pp. 385-392, the
contents of which are hereby incorporated by reference.
[0066] The rate of biodegradation may be controlled by the relative
amount of the compound use to increase the biodegradability of the
ink, or the product produced by the polymerized ink.
[0067] FIG. 6 shows a sematic layout of an ink mixing and print
nozzle of a preferred embodiment of the present invention.
[0068] In a preferred embodiment, the ink may contain structural
material ingredients; ingredients to form a porous, resorbable,
matrix; and additives such as, but not limited to, synthetic BMPs,
antibiotic chemicals, anti-inflammatory chemicals and radiopaque
chemicals, or some combination thereof.
[0069] The structural material ingredients may, for instance,
include a substance such as, but not limited to, Hydroxyapatite,
allograft particulate bone, xenograft particulate bone or some
combination thereof.
[0070] The ingredients to form a porous, resorbable matrix may
include substances such as, but not limited to, methyl
methacrylate, cellulose, resorbable cements, or precursors to
resorbable cements or some combination thereof.
[0071] Antibiotic additives may include any suitable antibiotic, or
antibiotic combinations, such as, but not limited to,
demeclocycline, doxycycline, minocycline, oxytetracycline,
tetracycline, thiamphenicol, ciprofloxacin, enoxacin, gatifloxacin,
levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid,
norfloxacin, ofloxacin, bacitracin, colistin,
amoxicillin/clavulanate, ampicillin/sulbactam,
piperacillin/tazobactam, ticarcillin/clavulanate, or some
combination thereof.
[0072] In a preferred embodiment, the ink may, for instance, be
supplied in the form of a precursor powder 190 and a precursor
liquid 195. These may be feed to separate containers in the 3-D
printer. Prior to printing, a quantity of the precursor powder 190
and the precursor liquid 195 may be mixed to form the ink 150 to be
used for printing the custom bone graft 120. The printing may be
accomplished by delivering quantities of the ink 150 via a suitably
sized print nozzle 235 that may be moved in a raster scan 230 with
respect to the custom bone graft 120 being printed.
[0073] The precursor powder 190 of the ink 150 may, for instance,
contain a variety of ingredients such as, but not limited to,
demineralized allograft bone matrix (DMB) 145, sucrose crystals
170, radical polymerization initiator 175 or some combination
thereof.
[0074] The radical polymerization initiator 175 may, for instance,
be a compound such as, but not limited to, di-benzoyl peroxide
(BPO).
[0075] The precursor liquid 195 may for, instance, contain a
variety of ingredients such as, but not limited to, methyl
methacrylate (MMA) 165, a radio-pacifier 185, an antibiotic 180,
and a compound to increase the biodegradability 265, or some
combination thereof.
[0076] The radio-pacifier 185 may, for instance, be a compound such
as, but not limited to, zirconium dioxide (ZrO.sub.2) or barium
sulphate (BaSO.sub.4) or some combination thereof.
[0077] The antibiotic 180 may, for instance, be a compound such as,
but not limited to, amoxicillin, doxycycline, gentamicin or
clindamycin or some combination thereof.
[0078] The compound to increase the biodegradability 265 may, for
instance, be a compound such as, but not limited to, cellulose
acetate (CA), or cellulose acetate phthalate (CAP) or some
combination thereof.
[0079] FIG. 7 shows a sematic flow diagram of representative steps
of a preferred embodiment of the present invention.
[0080] In Step 701 "Obtain 3-D Image of Graft Location", the
patient may be imaged using one of a number of well-known
techniques for obtaining a 3-D image such as, but not limited to, a
cone beam 3-D camera, computer aided tomography, 3-D laser cameras
or a combination thereof.
[0081] In Step 702 "Create 3-D Model of Custom Bone Graft", the
images obtained in step 701 may be used by a suitably constructed
computer program operable on a suitable digital data processor, to
generate a 3-D model of a custom bone graft for the patient. In
this step, the computer program may also use a database of standard
models of human body parts to provide guidance on areas that may
not be adequately described or detailed by the 3-D images. The
custom bone graft may also include provision for locating fixation
screws that might be added using guidance from a qualified
professional.
[0082] Fixation screws, including their size, location and
orientation may be designed on the computer model by a competent
expert. Holes for drill sleeves may then be designed into the
custom bone graft. Sleeves may then be inserted into the bone
graft. The surgeon may then be supplied with directions and the
drill size and depth required for each fixation screws. The drill
may, for instance, incorporate a stop to prevent it penetrating too
deeply into the bone of the graft recipient, or into vital
structures within the bone such as, but not limited to, arteries,
veins or nerves. Once the holes are drilled, the sleeves may be
removed and the fixation screws inserted by the surgeon to hold the
graft in place. The fixation screws may for instance be made of
stainless steel, titanium or resorbable screws, and may be supplied
with the graft.
[0083] In Step 703 "Mix Precursor Powder & Liquid to Form Ink",
precursors of the ink may be mixed in relatively small batches. The
size of the batches mixed into ink may depend on the print speed of
the 3-D printer, the print nozzle size of the printer, and the
constituents of the precursors, as once mixed, the ink will begin
to polymerize with the viscosity of the ink increasing with time.
Only as much ink as may be used by the 3-D printer in the time the
ink is deliverable by the print nozzle may be mixed at any one
time.
[0084] In Step 704 "Final Layer Printed?" the 3-D printer may first
check to see if it has printed all the layers required to produce
the custom bone graft. These layers may have been provided by a
programmed module operative on a digital data processing device,
and may be the 3-D model of the custom bone graft reduced to
consecutive slices that printed in the correct order may result in
the required custom bone graft.
[0085] In Step 705 "Print Next Layer", the 3-D printer may, if the
final layer has not yet been printed, print the next layer. This
may be done by, for instance, moving the print nozzle in a raster
fashion, depositing ink where required. The printing is preferably
performed in a sterilized environment.
[0086] In Step 707 "Post Print Processing of Graft", once the 3-D
printer has printed all the required layers that constitute the
custom bone graft, the bone graft may undergo post print
processing. This post processing step may, for instance, include
actions such as, but not limited to, dissolving out the sucrose
crystals to provide a porous structure and sterilization of the
custom bone graft.
[0087] In Step 708 "Insert Custom Bone Graft at Intended Graft
Location" the printed and processed custom bone graft may now be
inserted into the patient at the intended graft location.
[0088] In alternate embodiments, the ink may include demineralized
xenograft bone, synthetic bone substitutes, and other slow
reabsorbing biocompatible, bioactive adhesives.
[0089] Alternate formulations of the printing ink may, for
instance, include artificial bone substitutes such as, but not
limited to, hydroxyapatite, synthetic calcium phosphate ceramic.
These may be used instead of, or with natural bone particulates
such as, but not limited to, allograft particulate bone, or
xenograft particulate bone, or some combination thereof. These may,
for instance, be used with synthetically produced bone
morphogenetic agents such as, but not limited to, recombinant human
Bone Morphogenetic Protein-2 (rhBMP-2).
[0090] Alternate inks may also, or instead, use other
biocompatible, bio-active adhesives such as, but not limited to
glass polyalkenoate cements, oleic methyl ester based adhesives, or
some combination thereof.
[0091] Although producing the custom bone grafts has been discussed
with respect to 3-D printing, some or all of the machining of the
custom bone grafts may be done using more conventional machining
such as computer numerical control (CNC) milling, drilling or
routing machines. The holes for the fixation screws may, for
instance, be drilled by CNC machine after the custom graft is
produced, or support structure necessary during the printing of a
complex shape may be removed by CNC machining, or a starting
template may be CNC machined from natural or synthetic bone
material to reduce the printing time of the entire custom
graft.
[0092] In order to do such machining the digital processor 240 may
generate a 3-D model in a suitable computer language such as, but
not limited to, G-code that may enable a CNC machine to machine a
block of bone substitute material. The block of bone material may,
for instance, be a material such as, but not limited to,
REPROBONE.RTM. material as supplied by Ceraymisys, Ltd. of
Sheffield, England. The material used to create the custom bone
graft may also, or instead, be a calcium phosphate material such
as, but not limited to, hydroxyapatite.
[0093] In a preferred embodiment, the machining may, for instance,
be accomplished using a multi-axis CNC milling machine such as, but
not limited to, a LAVA.TM. CNC 500 milling system manufactured by
3M of Minneapolis, Minn.
[0094] In a further preferred embodiment of the invention, a
semipermeable, resorbable membrane may be printed on top of the
bone graft using a second ink. Such a membrane may, for instance,
be made of a co-polymeric blend of poly-vinyl alcohol (PVA) and
poly-vinyl pyrrolidone (PVP), as discussed in, for instance, U.S.
Pat. No. 7,476,250 issued to Mansmann on Jan. 13, 2009 entitled
"Semi-permeable membranes to assist in cartilage repair", the
contents of which are hereby incorporated by reference. The
semipermeable, resorbable membrane may, for instance, be extend
beyond the perimeter of the bone graft in some or all portions of
the perimeter, by an amount that may be as much as 1 cm, but is
more preferably 0.5 cm.
[0095] In yet a further preferred embodiment of the invention, a
custom bone graft 120 may be produced using a graft negative mold
305. The graft negative mold 305 may, for instance, be generated
using a 3-D digital graft model 310 produced from a 3-D image 105
obtained using a X-ray imaging machine 155 such as, but not limited
to, a cone-beam X-ray imaging machine 315.
[0096] FIG. 8 shows a cone-beam X-ray imaging machine 315 to
perform a scan of a patient 320. A cone-beam X-ray imaging machine
315 typically contains an X-ray generator 325 and a digital X-ray
sensor 330. The X-ray generator 325 and the digital X-ray sensor
330 may, for instance, be housed at opposite extremities of a
C-shaped housing 335. The X-ray generator 325 may emit a conical
beam of X-rays 340 as the C-shaped housing 335 is rotated 345
around the patient 320. The data captured by the digital X-ray
sensor 330 may then be sent to a digital computer 350 that may be
running suitable software to convert that data into a 3-D image 360
of a bone defect 355 aka an intended graft location 370. The 3-D
image 360 of a bone defect may, for instance, be displayed on a
digital display 365.
[0097] FIG. 9 shows a sectional view of a 3-D image 360 of a bone
defect such as, but not limited to, bone and/or cartilage tissue
lost to trauma, surgery, infection, normal aging or anatomic
abnormalities due to any pathology. This method may, for instance,
be useful in oral maxillofacial surgery, dental implants,
orthopedic surgery or any type of reconstructive hard tissue
surgery.
[0098] FIG. 10 shows a sectional view of a computer generated 3-D
positive image 375 of a required custom bone graft 120 to be
located at a bone site 395.
[0099] In a preferred embodiment, the 3-D positive image 375 of a
required custom bone graft may also include additional requirements
such as, but not limited to, any required locating screws 380, or
guide paths for screws or tacks to fix the graft in place, space
for adhesive 385 and any required structural reinforcement 390, or
guide holes to accommodate reinforcement pins, or some combination
thereof.
[0100] FIG. 11 shows a sectional view of a computer generated model
of a negative mold 405 of a required graft. The negative mold 405
may, for instance, include a top of a negative mold 410, a left
bottom of a negative mold 415, and a right bottom of a negative
mold 420, or some combination thereof. The negative mold 405 of a
required graft may, for instance, include suitable relief vent
holes 425, locating cones 430, or some combination thereof. The top
of a negative mold 410 may, for instance, be also include suitable
locating keys 435 or guide paths for additions such as, but not
limited to, locating screws or tacks 380, structural reinforcement
pins 390 or some combination thereof.
[0101] In a preferred embodiment, the negative mold 405 of a
required graft may be made using a 3-D printer and suitable
polymers or photopolymers. The negative mold 405 of a required
graft may also be made, wholly or in part, using a CNC machine such
as, but not limited to, a CNC router, or a combination of 3-D
printing and CNC machining.
[0102] FIG. 12 shows a sectional view of a negative mold being used
to produce a required graft. The negative mold 405 of a required
graft may, for instance, be first coated with a suitable release
agent 440 and any necessary place holders 450 for any structural
reinforcement 390 or locating screws 380 or a combination thereof.
An FDA approved, porous, biodegradable, biocompatible material 445
that is conducive to osteoinduction and has a load bearing strength
comparable to bone, to produce said custom bone graft may then be
poured, placed or inserted into the negative mold 405 of a required
graft.
[0103] The materials used in producing the customized bone graft
from the negative mold may include any of the appropriate
materials, and combinations of materials, described above such as,
but not limited to, demineralized allograft bone matrix (DMB), or
porous Poly Methyl Methacrylate (PMMA) 140 and recombinant human
Bone Morphogenetic Protein-2 (rhBMP-2), or some combination
thereof.
[0104] In a preferred embodiment of the present invention, the
material may be a mixture such as, but not limited to, Calcium
Sulfate hemihydrate, aka Plaster of Paris, demineralized freeze
dried bone (DFDB), or freeze dried bone (FDB), Bone Morphogenetic
Proteins (BMP) and an antibiotic such as, but not limited to,
Odxucicline.
[0105] Further materials including, but not limited to, solidifying
resorbable or non resorbable possibly osteoconductive,
osteoinductive medium that may be placed inside the negative mold.
Such a medium may, for instance, be a medium such as, but not
limited to, polymethylmethacrylate (PMMA), Fibrin Glue,
Hydroxyapatite cements or Bio-glass or some combination thereof.
Other biomaterials such as, but not limited to, coral, bone-derived
materials, bioactive glass ceramics, and synthetic calcium
phosphate that may have been mixed with fibrin sealant bone
grafting material that may be added by an operator (any particulate
material available may function) as well as BMPs, antibiotics or
other additives deemed necessary. Material that may be in excess of
the required amount may be placed so as to accommodate any
resorption of the graft. The negative lid may be placed by, for
instance, guiding cones that may engage negative mold cone holes.
Excess material may be squeezed out of the negative lid through
suitably place relieve vents and be removed while the bone graft is
still in a gelatinous, or liquid state.
[0106] The porous, biodegradable, biocompatible material 445 may be
allowed to, or induced to, set, thereby creating a required custom
bone graft 120.
[0107] FIG. 13 shows a sectional view of a graft being placed
during surgery. The intended graft location 370 may first be coated
with a bone adhesive 455. The custom bone graft 120, including any
necessary structural reinforcement 390 that may be incorporated
into it, may then be placed in the intended graft location 370. The
custom bone graft 120 may then be secured in the intended graft
location 370 by a suitable means such as, but not limited to, one
or more locating screws 380 or tacks, that may be bio-inert and may
be bio-absorbable. The structural reinforcement 390 and locating
screws 380 are preferably biocompatible and may be biodegradable.
Suitable biocompatible materials include compositions such as, but
not limited to, plastics such as PMMA and stainless steel,
polygluconate co-polymer (PGACP) or self-reinforced poly-L-lactic
acid polymer (PLLA) or some combination thereof.
[0108] FIGS. 14 A-D are illustrative of steps that may be used in
the process of fabricating a required complex long bone graft
460.
[0109] FIG. 14 A shows a required complex long bone graft that may
be required 460.
[0110] FIG. 14 B shows a negative mold for a portion 465 of the
required complex long bone graft 460. In the instance shown in FIG.
14 B, the negative mold is designed to produce one half of the bone
graft. The negative mold may include a top of a negative mold 410,
a left bottom of a negative mold 415 and a right bottom of a
negative mold 420 as well as locating cones 430 and corresponding
locating indents 470, and vent holes 425.
[0111] FIG. 14 C shows a negative mold being used to produce a
portion of the required complex long bone graft. The negative mold
405 of a portion of the required graft, containing any required
structural reinforcement 390, may have been coated with a suitable
release agent and then filled with an appropriate porous,
biocompatible material 125.
[0112] FIG. 14 D shows a complex long bone graft 460 composed of
two portions 465 of the bone graft that may contain structural
reinforcements 390 and held together by one or more locating screws
380.
[0113] Although this invention has been described with a certain
degree of particularity, it is to be understood that the present
disclosure has been made only by way of illustration and that
numerous changes in the details of construction and arrangement of
parts may be resorted to without departing from the spirit and the
scope of the invention. cm What is claimed:
* * * * *