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`Smith & Nephew Ex. 1044
`IPR Petition - USP 9,295,482
`
`

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`5,370,692
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`Page 2
`
`' OTHER PUBLICATIONS
`
`the Fourth World Biomaterials Congress, Berlin, Fed-
`eral Republic of Germany, Apr. 1992, p. 564.
`
`M. Erbe et a1., “Geometrically Surface Structured
`Stereolithography Acrylic Resin and Titanium Im-
`plants”, Proceedings of the Fourth World Biomaterials
`Congress, Berlin, Federal Republic of Germany, Apr.
`1992, p. 165.
`
`S. J. Bresina, “The Treatment of Bone Defects”, Pro-
`ceedings of the Fourth World Biomaterials Congress,
`
`Berlin, Federal Republic of Germany, Apr. 1992, p.
`207.
`
`T. Truby, “Growing a Human Skull”, Med. Equip.
`Designer, Jul. 1992, pp. M8—l0.
`M. Burns, “Introduction to Desktop Manufacturing and
`Rapid Prototyping”, Rapid Prototyping: System Selec-
`tion and Implementation Guide, 1992, pp. 2-6.
`T. Ward et al., “The Evaluation of Component Prototy-
`ping and Reverse Engineering Systems”, Final Report
`to US. Army Chemical Research, Development and
`Engineering Center, Nov. 1990, pp. 1-39.
`
`-2-
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`

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`U.S. Patent
`
`Dec. 6, 1994
`
`Sheet 1 of 2
`
`5,370,692
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`CREATE CAD FILE
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`CREATE "SLICED" FILE
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`
` |lIII||n‘.““
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`DDDUDDUDUUDC3
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`DDDDDDDDDDDC3
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`DDDDDUDDDDDD
`UDDDDDDUDUD
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`EZDDDDUDDDUDD
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`
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`UDDUUDDUDDDC3
`DDUUDUDUUUDC3
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`DDDDDDDDDDDD
`DDDDDDDUDUD
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`EJDDDUDDDDDUD
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`SPREAD POWDER
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`PRINT LAYER
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`DROP PISTON
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`REPEAT CYCLE
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`FINISHED PART
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`L"§§1NLT“E‘$ER
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`FIG- 1
`PRIOR ART
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`-3-
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`

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`U.S. Patent
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`Dec. 6, 1994
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`Sheet 2 of 2
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`5,370,692
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`2
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`CT SCAN OF BONE
`
`A4
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`5
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`TRANSLATION OF CT .FILE
`TO STANDARD BINARY
`OR ASCI FORMAT
`
`IMPORT OF TRANSLATED
`FILE TO 3-D DATA
`MANIPULATION PACKAGE
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`7
`
`AREA PERIMETERS
`OPTIMIZED (MANIPULATED
`FOR SMOOTHNESS.
`SIZE, ETC.)
`
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` 6
`2-D RECOGNITION OF
`DATA BY CT LAYER TO
`FORM AREA
`PERIMETER(S)
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`8
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`AREA PERIMETERS
`
`STACKED AND SURFACE
`MODEL FORMED
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`11
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`REPRODUCTION MODEL
`'
`SLICED FOR
`FFM PROCESS
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`9
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`SURFACE MODEL
`OPTIMIZED (SMOOTHED,
`ALIGNED, ORIENTED,
`ECT.)
`FOR FFM
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`REPRODUCTION CREATION
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`10
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`STL FILE FORMAT
`EXPORTED FOR
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`1 2
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`BONE REPRODUCTION
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`MANUFACTURED
`
`BY VENDORS
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`FIG-2
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`5,370,692
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`RAPID, CUSTOMIZED BONE PROSTHESIS
`
`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 manufactur-
`ing techniques to replicate the hard tissue being re-
`placed by the prosthesis.
`BACKGROUND ART
`
`10
`
`Wounds of war have always horrified civilian popu-
`lations. Indeed, for all human history, the recognition of
`attendant physical mutilation has probably been the 15 1,
`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 practi-
`cal. However, the parallel revolutions in computer sci-
`ence and human-focused biotechnology now open an
`unprecedented opportunity to modern military medi-
`cine: to make a wounded soldier whole and functional
`to a degree that rivals mythology.
`CERAMIC IMPLANTS
`
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`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:
`
`30
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`1. glasses or glass-ceramic, primarily compositions
`from the SiO2——-P2O5—CaO—--Na2O system, or
`2. calcium phosphate compositions, primarily B-
`tricalcium phosphates (B-TCP), Ca3(P04)z and
`calcium hydroxylapatite (HA), Ca1o(PO4)5(OH)z,
`and combinations of the two.
`
`Generally, the calcium phosphate ceramics may be
`somewhat easier to produce and/or obtain commer-
`cially, and are receiving an increasing share of the re-
`search and clinical attention. B-TCP is normally ob-
`served 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 osteoprogeni-
`tor cells), as opposed to osteoinductive, which implies a
`more active process in which the matrix recruits osteo-
`progenitor 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;
`Chin
`
`Zygomatic;
`
`Reconstruction-—Periodontal; Mandibular; Orthog-
`nathy; Bone Grafting; Cranioplasty; Orbital floor;
`Anterior nasal spine
`Prosthetic Implants
`Subperiosteal
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`Endostea1—Endosseous implants; Endodontic pins:
`Orthodontic pins
`Transosseous——Transmandibu1ar
`Otological Applications
`Ossicular reconstruction
`Canal wall prostheses
`
`ORTHOPEDIC USES
`Bone Graft Substitutes
`
`Augmentation—Delayed or failed unions; Arthrode-
`sis (fusion of joint); Bone graft donor sites; Me-
`chanically stable cystic defects; Revision or pri-
`mary joint replacement
`Replacement—Vertebral body defects; Segmental
`one defects;
`Mechanically unstable subchondral defects (e.g., tib-
`ial 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 ther-
`3P)’;
`Local delivery of bone growth factors or osteoinduc-
`tive factors
`
`HA, the predominant ceramic in bone, and the com-
`position of the bond between bioactive ceramics and
`bone, has been assessed to provide the following advan-
`tages in dental
`irnplantations:
`l. 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 re-
`sults; and 9. no need for perfect oral hygiene on the part
`of the patient. Most of these advantages cart be antici-
`pated 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
`B-TCP to produce a range of rates.
`For use in these applications, calcium phosphate ma-
`terials are currently produced in a variety of formats,
`normally by sintering particulate solids:
`Particulates—range of particle sizes; variable poros-
`ity.
`Moldable Forms—pastes; self-setting slurries or pre-
`formed shapes.
`Block Forms—-designed geometries such as rods,
`cones, spheres, and discs; variable micro- and mac-
`roporosity.
`Coatings—applied to a preformed substrate by tech-
`niques such as plasma spraying, flame spraying,
`electrophoresis, ion beam—radio frequency sput-
`tering, 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 carmot be used where implant
`strength is required and 2) particle migration often oc-
`curs 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 implanta-
`tion.
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`In clinical applications in which strength of the ce-
`ramic implant is a significant factor (e.g., craniofacial
`augmentation or
`reconstruction; bone replacement;
`fracture fixation), block forms of the material are re-
`quired and shaping of the implant becomes more diffi-
`cult.
`
`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. Gener-
`ally, pores at least 200-300 micrometers in diameter
`(referred to as macroporosity) are believed to be neces-
`sary in osteoconductive materials to permit ingrowth of
`vasculature and osteogenic cells. Microporous ceram-
`ics, on the other hand, with pores only a few microme-
`ters 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 “re-
`plamineform” 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 ,u.m diameter. HA materials of this type are mar-
`keted by Interpore Orthopedics, Inc. of Irvine, Calif.
`An alternative approach to the fabrication of custom-
`ized ceramic implants, involving a CT-integrated com-
`puterized milling operation to produce molds or im-
`plants, has been clinically tested for facial reconstruc-
`tion. 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 anesthe-
`tized, and generally are much more accurate recon-
`structions of the desired bone than can be accom-
`plished 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 ce-
`ramic, or by preparing a “negative” mold of the im-
`plant, then molding the implant using a formable ce-
`ramic composition. Direct milling is difficult with mac-
`roporous bioceramics, including the coralline HA mate-
`rials. 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 signif-
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`icant constraint when using the composite molding
`technique.
`
`FREE-FORMING MANUFACTURING
`
`The terms free-forrning manufacturing (FFM), desk-
`top manufacturing, rapid prototyping, and several oth-
`ers, all describe the new manufacturing processes that
`enable the physical fabrication of three-dimensional
`computer models with a minimum of human interac-
`tion. 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 Sinter-
`ing” 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 commercial-
`ize 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 de-
`pends 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 mate-
`rial. Although DTM markets only polymer-based man-
`ufacturing at this time, it is currently in the research
`phase of developing ceramic capabilities. To date, fabri-
`cation of ceramics, including alumina/phosphate com-
`posites, have been demonstrated in the DTM process.
`The MIT process, which has not been commercial-
`ized 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 Com-
`puted 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 se-
`lection process can be based upon matching grey-scale
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`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 256x256 or 512x 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 rela-
`tively crude FFM models of complex anatomical struc-
`tures 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 re-
`quires integration of several independently developing
`technologies designed to: provide physical characteris-
`tics of the patient’s original hard tissue; permit custom-
`ized 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 pros-
`thetic 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 sec-
`ondary 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 mate-
`rial to produce the implant. The unique porosity charac-
`teristics (potentially adaptable to specific patients) of
`the missing hard tissue structures may then be repro-
`duced. 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 ap-
`propriate 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 ap-
`propriate 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.
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`In describing the preferred embodiment of the inven-
`tion which is illustrated in the drawings, specific termi-
`nology will be resorted to for the sake of clarity. How-
`ever, 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 simi-
`lar purpose.
`
`DETAILED DESCRIPTION
`
`2.
`
`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 com-
`pensate for anticipated healing responses or to pro-
`vide for surgical-assist structures);
`is composed of a ceramic material that exhibits
`properties similar to bone, and that presents physi-
`cal, chemical and surface properties that facilitate
`bone cell function and production of new bone;
`3. is designed to maximize the rate of cellular coloni-
`zation of the ceramic matrix and to direct the pro-
`duction of new bone—altematively, 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 cus-
`tomized prosthetic device by use of available com-
`puterized imaging techniques (for example, Com-
`puterized Tomography, CT, or Magnetic Reso-
`nance 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 compen-
`sate for, or optimize, anticipated healing processes;
`. 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 pro-
`duce 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 im-
`plantation 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 mate-
`rials described above in the Background Art may be
`used. Additionally, implant devices may also be con-
`structed from calcium carbonate, a resorbable ceramic,
`alumina or other biocompatible ceramics. Unique ce-
`ramic processing may be required for each specific
`approach. In the A1203/NI-I41-I2PO4 system, for exam-
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`ple, alumina has a melting point of 2045° C., while
`NH4H2PO4 has a melting point of 190° 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-melt-
`ing-point phosphate melts to form a glassy material and
`bonds the alumina particles. A secondary heat treat-
`ment is necessary to develop the full strength of the
`material. During heat treatment at 850° C., the follow-
`ing net reaction takes place.
`
`A123 + 2NH4H2P04(81RsSy)-2A1-
`PO4+ 2NH3(8) + 2}-[20 (g)
`
`The reaction results in an A1203/AIPO4 composite
`where aluminum phosphate forms a thin layer around
`the alumina particles. The AIPO4 volume fraction de-
`pends on the initial composition.
`FFM technology presents a unique capability to in-
`troduce 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 ce-
`ramic; 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 poly-
`meric FFM reproduction may also be done using photo-
`active polymer techniques. In such a technique a mono-
`mer is polymerized at selected regions by an incident
`laser beam to create a solid polymeric model. The ap-
`proach 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 recog-
`nized 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 poly-
`meric 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 mono-
`mer 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 composi-
`tion. For example, the replica may be formed of calcium
`carbonate or tricalcium phosphate and then converted
`
`to hydroxyapatite by conventional processing tech-
`niques.
`While certain preferred embodiments of the present
`invention have been disclosed in detail, it is to be under-
`stood that various modifications may be adopted with-
`out departing from the spirit of the invention or scope
`of the following claims.
`We claim:
`
`1. A method for fabricating an implantable device,
`the method comprising:
`fabricating an approximate replica of bone by sequen-
`tially solidifying adjoining, cross-sectional inter-
`vals of a fluid material along an axis.
`2. A method in accordance with claim 1 wherein a
`design data base is first generated by scanning at least a
`portion of an animal's body using imaging techniques to
`generate a design data base of measurement data repre-
`senting size and shape of the bone in a three dimensional
`coordinate system and then fabricating said replica in
`correspondence with the data in said design data base.
`3. A method in accordance with claim 2 wherein the
`step of solidifying a fluid material comprises bonding
`ceramic particles.
`4. A method in accordance with claim 2 wherein the
`scarming step comprises generating the data base by
`scaiming a body part of a healthy individual animal and
`archiving the data base for subsequent use.
`5. A method in accordance with claim 4 wherein the
`method further comprises modifying the data base to
`make selected changes in the size and shape of the bone
`represented by the data base.
`6. A method in accordance with claim 1 wherein the
`step of solidifying a fluid material comprises bonding a
`photo-active polymeric material.
`7. A method in accordance with claim 1 wherein the
`step of solidifying a fluid material comprises sintering
`ceramic particles.
`8. A method in accordance with claim 1 wherein the
`step of solidifying a fluid material comprises bonding
`particles a first ceramic material together with particles
`of a second ceramic material.
`9. A method in accordance with claim 1 wherein the
`step of solidifying fluid material comprises cementing
`particles together with a polymer.
`10. A method in accordance with claim 1 wherein the
`fluid material comprises ceramic particles suspended in
`a liquid monomer and wherein the monomer is poly-
`merized to form a solid polymer network and wherein
`at least a part of the polymer is then removed.
`11. A method in accordance with claim 1 wherein the
`fluid material comprises ceramic particles and wherein
`the solidified replica is then reacted with an agent to
`change its composition.
`12. A customized implantable device prepared by the
`method of claim 1.
`
`13. A customized implantable device prepared by the
`method of claim 2.
`*
`#
`t
`1
`t
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`65
`
`-8-