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TECHNICAL FIELD
This invention relates to the fabrication of prosthetic implants to replace
bone and more particularly relates to the use of computer based imaging
and manufacturing techniques to replicate the hard tissue being replaced
by the prosthesis.
BACKGROUND ART
Wounds of war have always horrified civilian populations. Indeed, for all
human history, the recognition of attendant physical mutilation has
probably been the single most effective limitation on the frequency and
scale of conflicts. It is only within the past century that even crude
forms of reconstructive surgery were practical. However, the parallel
revolutions in computer science and human-focused biotechnology now open
an unprecedented opportunity to modern military medicine: to make a
wounded soldier whole and functional to a degree that rivals mythology.
CERAMIC IMPLANTS
It has been only slightly more than two decades since the discovery by
Hench and his co-workers that a direct chemical bond can form between
certain "bioactive" glass-ceramic materials and bone, thereby potentially
stabilizing dental or orthopaedic implants made from these materials. In
the meantime, the investigation of other chemical formulations (including
many ceramics and composites), physical forms (e.g., dense or porous
particulates and solids, coatings, and composites), and clinical
applications have progressed rapidly.
Most research into the use of bioactive materials is now focused on either:
1. glasses or glass-ceramic, primarily compositions from the SiO.sub.2
--P.sub.2 O.sub.5 --CaO--Na.sub.2 O system, or
2. calcium phosphate compositions, primarily .beta.-tricalcium phosphates
(.beta.-TCP), Ca.sub.3 (PO.sub.4).sub.2 and calcium hydroxylapatite (HA),
Ca.sub.10 (PO.sub.4).sub.6 (OH).sub.2, and combinations of the two.
Generally, the calcium phosphate ceramics may be somewhat easier to produce
and/or obtain commercially, and are receiving an increasing share of the
research and clinical attention. .beta.-TCP is normally observed to
biodegrade much more rapidly than HA, which until recently was believed to
be non-resorbable. Such bioactive ceramics are generally considered to be
osteoconductive (i.e., providing an appropriate scaffold that permits
ingrowth of vasculature and osteoprogenitor cells), as opposed to
osteoinductive, which implies a more active process in which the matrix
recruits osteoprogenitor cells from the local tissue or circulation.
Current or potential applications for these materials include:
DENTAL AND OTHER HEAD AND NECK USES
Craniofacial Applications
Augmentation--Ridge; Mandibular; Zygomatic; Chin
Reconstruction--Periodontal; Mandibular; Orthognathy; Bone Grafting;
Cranioplasty; Orbital floor; Anterior nasal spine
Prosthetic Implants
Subperiosteal
Endosteal--Endosseous implants; Endodontic pins: Orthodontic pins
Transosseous--Transmandibular
Otological Applications
Ossicular reconstruction
Canal wall prostheses
ORTHOPEDIC USES
Bone Graft Substitutes
Augmentation--Delayed or failed unions; Arthrodesis (fusion of joint); Bone
graft donor sites; Mechanically stable cystic defects; Revision or primary
joint replacement
Replacement--Vertebral body defects; Segmental bone defects;
Mechanically unstable subchondral defects (e.g., tibial plateau fractures
and large traumatic defects; Grafting around prostheses used for
mechanical fixation
Fracture Fixation Materials
Fracture fixation devices such as plates, screws and rods;
Endoprosthese such as joint replacements
Coating for Fixation
Fixation of implant to bone in joint replacement;
Coated internal fixation devices
Drug Delivery Implants
Local adjuvant chemotherapy; Local antibiotic therapy;
Local delivery of bone growth factors or osteoinductive factors
HA, the predominant ceramic in bone, and the composition of the bond
between bioactive ceramics and bone, has been assessed to provide the
following advantages in dental implantations: 1. biocompatibility; 2.
absence of antigenic response; 3. availability; 4. ability to use local
anesthesia during implantation; 5. low risk of infection; 6. low risk of
permanent hyperesthesia; 7. lack of significant resorption; 8. high rate
of good results; and 9. no need for perfect oral hygiene on the part of
the patient. Most of these advantages cart be anticipated in orthopedic
applications as well, although the need for a more rapid rate of
resorption has been the incentive for investigation of mixtures of HA and
.beta.-TCP to produce a range of rates.
For use in these applications, calcium phosphate materials are currently
produced in a variety of formats, normally by sintering particulate
solids:
Particulates--range of particle sizes; variable porosity.
Moldable Forms--pastes; self-setting slurries or preformed shapes.
Block Forms--designed geometries such as rods, cones, spheres, and discs;
variable micro- and macroporosity.
Coatings--applied to a preformed substrate by techniques such as plasma
spraying, flame spraying, electrophoresis, ion beam--radio frequency
sputtering, dip coating, and frit-slurry enameling.
Particulate formats were among the first bioactive ceramics taken to the
clinic, but these materials have the disadvantages 1) they cannot be used
where implant strength is required and 2) particle migration often occurs
in the implant site, decreasing the effectiveness of the material. To
minimize the latter problem, many attempts have been made to use
biodegradable materials to agglomerate and mold the particles during
implantation.
In clinical applications in which strength of the ceramic implant is a
significant factor (e.g., craniofacial augmentation or reconstruction;
bone replacement; fracture fixation), block forms of the material are
required and shaping of the implant becomes more difficult.
Perhaps the most important physical properties of bioactive ceramics are
the volume and size of the pores within the material, which strongly
influences both the tensile and compressive strengths of the material and
the rate of resorption and cellular colonization. Generally, pores at
least 200-300 micrometers in diameter (referred to as macroporosity) are
believed to be necessary in osteoconductive materials to permit ingrowth
of vasculature and osteogenic cells. Microporous ceramics, on the other
hand, with pores only a few micrometers in diameter, do not permit
cellular invasion, and in most cases, are likely to be more difficult to
stabilize in the implant site. An example of an implant material selected
for its consistent macroporosity is the "replamineform" calcium phosphate
structures derived by chemically transforming a variety of corals
(initially calcium carbonate), which are composed of a network of
interconnecting pores in the range of approximately 200 .mu.m diameter. HA
materials of this type are marketed by Interpore Orthopedics, Inc. of
Irvine, Calif.
An alternative approach to the fabrication of customized ceramic implants,
involving a CT-integrated computerized milling operation to produce molds
or implants, has been clinically tested for facial reconstruction.
Advantages of this prefabricated implant approach were identified as:
1. Contour (of facial implants) is to the underlying bone base (as opposed
to the surface of the skin by standard facial moulage techniques);
2. Formamina are localized (implants are designed to avoid nerve foramina);
3. Covered areas are "visible" (no interference in the design from hair or
dressings);
4. Soft-tissue contours can be evaluated;
5. Pre-existing implants can be evaluated;
6. Volume measurements can be obtained;
7. Local anatomy can be better visualized;
8. Models are provided for "practice surgery";
9. Templates can be designed for bone graft surgery;
10. An archive can be maintained for clinical re-evaluation and academic
study;
11. Prefabricated grafts minimize the time for implant sculpting in
surgery, while the patient is anesthetized, and generally are much more
accurate reconstructions of the desired bone than can be accomplished by
hand;
12. There is no need for a second surgical site, as in autogenous graft
surgery.
In the CT-integrated milling operation described, implants can be made
directly by milling the solid ceramic, or by preparing a "negative" mold
of the implant, then molding the implant using a formable ceramic
composition. Direct milling is difficult with macroporous bioceramics,
including the coralline HA materials. A moldable HA-collagen composite
material has, therefore, been clinically tested with good results in
low-strength indications. However, the composite is relatively friable,
loses strength when moistened, and is not suitable where structural
strength is required, for example, for long bone or mandibular
reconstructions. In addition, control of implant macroporosity is a
significant constraint when using the composite molding technique.
FREE-FORMING MANUFACTURING
The terms free-forming manufacturing (FFM), desktop manufacturing, rapid
prototyping, and several others, all describe the new manufacturing
processes that enable the physical fabrication of three-dimensional
computer models with a minimum of human interaction. All of the systems
that are on the market or in development are based upon mathematically
"slicing" a three dimensional Computer Aided Design (CAD) model and then
sequentially reconstructing the cross sections (slices) of the model on
top of one another using the manufacturing system's solid medium. One
supplier of FFM systems, 3-D Systems (Valencia, Calif.), markets a
"stereolithography" system based upon laser-mediated polymerization of
photo-sensitive liquid monomer. Of the FFM processes, only two are able to
work with ceramics: the "Selective Laser Sintering" system marketed by DTM
Corporation (Austin, Tex.) and the "3 Dimensional Printing" system under
development at the Massachusetts Institute Technology (Cambridge, Mass.).
Both processes can accept the industry standard STL file format, and both
research organizations are working with industry to commercialize the
respective processes.
The DTM process is based upon localized sintering of ceramic powder
material by a scanning laser beam. When the laser beam impinges on the
surface powder, it melts, and localized bonding between particles take
place. By selectively sintering sequential layers, the shape is built in a
matter of hours. The build rate depends on the complexity and size of the
part, power output of the laser, the coupling between the laser and the
material and the rheological properties of the material. Although DTM
markets only polymer-based manufacturing at this time, it is currently in
the research phase of developing ceramic capabilities. To date,
fabrication of ceramics, including alumina/phosphate composites, have been
demonstrated in the DTM process.
The MIT process, which has not been commercialized yet, is based upon
selective binding of a powder, using ink-jet techniques to distribute the
binding agent, as illustrated schematically in FIG. 1. Typical devices are
built from alumina powder bonded with colloidal silica, to reproduce a
typical ceramic shell.
CT IMAGING
In 1979 Houndsfield and Cormack were awarded the Nobel Prize in Medicine
for their contributions to Computed Tomography (CT). Since then virtually
every major hospital in the world has acquired the ability to perform CT.
As opposed to classical x-ray imagining, where a shadow image of a patient
volume is created, CT is a two step process where 1) the patient is imaged
at multiple angles through the rotation of an x-ray source, and 2) the
image is manipulated in the computer to create a series of sliced images
of the patient. Through the use of sophisticated computer algorithms, the
sliced information can be reconstructed to form three dimensional images
of the patient's tissue.
A complexity of the manipulation process to create the FFM design file is
the isolation of the specific tissue of interest from the surrounding
tissue, a process (often relatively subjective) termed "segmentation".
This selection process can be based upon matching grey-scale intensities
directly from the CT file without operator interaction.
In the CT process each volume pixel (voxel) in a patient cross section is
assigned a CT number (in Houndsfield units) based upon the physical
density of the material with respect to water. These numbers are stored in
256.times.256 or 512.times.512 square array format. This information is
manipulated in the computer to show corresponding grey or color scales for
selected tissue on the computer display. This array-formatted information
can also be transferred from the CT scanner into graphic engineering
computers for subsequent data manipulation as demonstrated, for example,
by Kaplan in the development of the integrated ceramic milling system.
Preliminary investigations, at the Medical College of Ohio, for example,
have also demonstrated that relatively crude FFM models of complex
anatomical structures can be prepared from MRI image files by the
stereolithography system from 3-D Systems.
BRIEF DISCLOSURE OF INVENTION
The invention involves a therapeutic approach that will create customized
prosthetic devices for hard tissue reconstruction. Rapid manufacturing
technology can produce implants that reproduce original tissue size and
shape while simultaneously maximizing the rate and quality of
cell-mediated hard tissue healing. This requires integration of several
independently developing technologies designed to: provide physical
characteristics of the patient's original hard tissue; permit customized
manufacturing by modern techniques; and optimize the rate of healing by
incorporating the patient's own bone-producing cells into the implant.
Imaging technology is used first to define hard tissue characteristics
(size, shape, porosity, etc.) before the trauma occurs ("pre-trauma" file)
by archival use of available imaging techniques (CT, MRI, etc.). The loss
of hard tissue is determined by imaging in the locale of the affected
tissue after the injury ("post-trauma" file). Then the physical properties
of the customized prosthetic device is specified by comparison of the
pre-trauma and post-trauma files to produce a solid model "design" file.
This specification may also involve secondary manipulation of the files to
assist in surgical implantation and to compensate for anticipated healing
process. The design file is mathematically processed to produce a "sliced
file" that is then used to direct a "rapid manufacturing" system to
construct a precise replica of the design file in a resorbable ceramic
material to produce the implant. The unique porosity characteristics
(potentially adaptable to specific patients) of the missing hard tissue
structures may then be reproduced. Autologous cells, derived from the
patient's post-trauma tissue, are cultured and then used to "seed" the
cells onto the ceramic matrix under conditions appropriate to maximize
cell attachment and function. The implanted cells will rapidly begin
producing new bone while other natural process slowly degrade and remove
the specialized ceramic matrix. The cell-seeded prosthesis is then
implanted at the trauma site and appropriate rehabilitation therapy is
begun.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a diagram illustrating the MIT powder process.
FIG. 2 is a flow chart illustrating the method of the present invention.
In describing the preferred embodiment of the invention which is
illustrated in the drawings, specific terminology will be resorted to for
the sake of clarity. However, it is not intended that the invention be
limited to the specific terms so selected and it is to be understood that
each specific term includes all technical equivalents which operate in a
similar manner to accomplish a similar purpose.
DETAILED DESCRIPTION
The invention is a new manufacturing approach that will provide customized
prosthetic devices for hard tissue reconstruction. Free-Form Manufacturing
(FFM) technology is a valuable new tool for making implants that reproduce
original tissue size and shape, and that maximize the rate of
cell-mediated hard tissue healing. The concept requires integration of
several independently developing technologies into the FFM system.
This strategy for reconstruction of traumatic, disease-related or surgical
loss of hard tissue is based on the hypothesis that therapy will be
optimally treated by a prosthesis that:
1. is matched to the precise anatomical dimensions of the original tissue
(or that may be modified to compensate for anticipated healing responses
or to provide for surgical-assist structures);
2. is composed of a ceramic material that exhibits properties similar to
bone, and that presents physical, chemical and surface properties that
facilitate bone cell function and production of new bone;
3. is designed to maximize the rate of cellular colonization of the ceramic
matrix and to direct the production of new bone--alternatively, a more
active approach is to optimize the device for seeding by autologous cells
derived from the patient.
Manufacturing steps in the process will include:
1. specification of the physical properties of the customized prosthetic
device by use of available computerized imaging techniques (for example,
Computerized Tomography, CT, or Magnetic Resonance Imaging, MRI) to
produce a solid model "design file" or CAD file. This specification may
also involve secondary manipulation of the files to assist in surgical
implantation and/or to compensate for, or optimize, anticipated healing
processes;
2. development of a mathematically processed design file to produce a
"sliced file" suitable for directing an FFM process;
3. construction of a precise replica of the sliced file by FFM in an
appropriate ceramic material to produce the implant.
This is an integrated system for imaging hard tissue, manipulating the
image file to produce the design file, processing the design file to drive
the FFM system and produce the implant, and optimizing the surgical
implantation and performance of such devices. It provides a method for
fabricating customized medical implant devices. This technology will be
used by the general orthopedic and dental communities as a specialized
service.
The glass, glass-ceramic or calcium phosphate materials described above in
the Background Art may be used. Additionally, implant devices may also be
constructed from calcium carbonate, a resorbable ceramic, alumina or other
biocompatible ceramics. Unique ceramic processing may be required for each
specific approach. In the Al.sub.2 O.sub.3 /NH.sub.4 H.sub.2 PO.sub.4
system, for example, alumina has a melting point of 2045.degree. C., while
NH.sub.4 H.sub.2 PO.sub.4 has a melting point of 190.degree. C.
Crystalline materials like ammonium phosphate and boron oxide show a
definite melting point which the viscosity drops sharply. When the
alumina/ammonium phosphate blend is processed with the DTM laser, the
lower-melting-point phosphate melts to form a glassy material and bonds
the alumina particles. A secondary heat treatment is necessary to develop
the full strength of the material. During heat treatment at 850.degree.
C., the following net reaction takes place.
Al.sub.2 .sub.3 +2NH.sub.4 H.sub.2 PO.sub.4 (glassy).fwdarw.2AlPO.sub.4
+2NH.sub.3 (g)+2H.sub.2 O (g)
The reaction results in an Al.sub.2 O.sub.3 /AlPO.sub.4 composite where
aluminum phosphate forms a thin layer around the alumina particles. The
AlPO.sub.4 volume fraction depends on the initial composition.
FFM technology presents a unique capability to introduce a defined porosity
into ceramic devices formed by aggregation (sintering) of particulate
substrates. For example, the porosity might be introduced or modified: 1.
by direct reproduction of a "porous" CT file; 2. by varying the particle
size distribution of the base ceramic; or 3. by post-treatment of formed
devices to remove specific agents included in the original
mixed-particulate bed (e.g., by differential solubility). These processes
offer a range of porosities available to tailor FFM devices to specific
applications.
The transformation of a CT bone image to a polymeric FFM reproduction may
also be done using photo-active polymer techniques. In such a technique a
monomer is polymerized at selected regions by an incident laser beam to
create a solid polymeric model. The approach for the fabrication of
ceramic devices is outlined in FIG. 2. Thus, fluid materials, either
liquids or masses of particles, are used to fabricate the replica of the
bone.
One key aspect of this manufacturing technique is the segmentation process,
in which the "bone" is recognized and separated from the other tissues in
the image, and the reproduction of a smooth bone surface, which entails
the manipulation of the data after segmentation.
The fluid materials may be ceramic particles which are sintered to form the
solidified replica using a DTM process. Ceramic particles may be cemented
together with a second type of ceramic particles or with a polymeric
phase. The replica may be formed by a laser photo polymerization process
(e.g. 3 D systems) in which ceramic particles are suspended in a liquid
monomer and then became trapped in the liquid polymer after
polymerization. Thereafter, a part or all of the polymer may be removed.
In addition, with the above processes in which the precursors of the final
ceramic product are formed by FFM methods, the resulting solid replica may
be converted to a desired composition. For example, the replica may be
formed of calcium carbonate or tricalcium phosphate and then converted to
hydroxyapatite by conventional processing techniques.
While certain preferred embodiments of the present invention have been
disclosed in detail, it is to be understood that various modifications may
be adopted without departing from the spirit of the invention or scope of
the following claims.
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