Customized implants for bone replacement

Abstract

The present invention relates to customized implants for bone replacement that are prepared from poly(ether ketone ketone) or PEKK, and to a computer-based imaging and rapid prototyping (RP)-based manufacturing method for the design and manufacture of these customized implants. The PEKK customized implants made using rapid prototyping demonstrate biomechanical properties similar (if not identical) to that of natural bone even when prepared without the use of processing aids such as carbon black and aluminum powder.

Claims

1. An implant or scaffold for bone replacement composed exclusively of pure selectively laser sintered poly(ether ketone ketone) (PEKK), the implant or scaffold being capable of ongrowth/ingrowth of tissues, the implant or scaffold not comprising calcium phosphate.

2. An implant or scaffold for bone replacement, comprising laser sintered poly(ether ketone ketone) (PEKK), the implant or scaffold being capable of ongrowth/ingrowth of tissues, the implant or scaffold not comprising calcium phosphate.

3. The implant or scaffold of claim 2, further at least one feature selected from the group consisting of a) openings configured to encourage bone, vascular and nerve in-growth, b) surface pores configured to hold therapeutic agents, and c) surface anchors and/or threaded holes.

4. The implant or scaffold of claim 3, wherein said surface pores hold one or more therapeutic agents selected from the group consisting of antibiotics, anti-coagulants, anti-inflammatory, anti-metabolites, antivirals, bone morphogenic proteins, cell adhesion molecules, growth factors, healing promoters, immunosuppressants, vascularizing agents, and topical anesthetics/analgesics; said therapeutic agents optionally being present in or on a carrier for controlled release.

5. The implant or scaffold of claim 4, wherein said carrier is encapsulated in a biocompatible or biodegradable polymer, or in a bioadhesive gel.

6. The implant or scaffold of claim 1, comprising a rigid implant having an inner core with a low porosity of 10 percent or less pores and an outer layer, said implant having a compressive strength ASTM #D695 of from 100 to 200 megapascals (Mpa) and a flexural modulus ASTM #D570 of greater than 3.5 gigapascals (GPa).

7. The implant or scaffold of claim 6, wherein said implant replaces a load-bearing bone.

8. The implant or scaffold of claim 7, wherein said load-bearing bone is selected from a spine, a long bone of an arm or a leg, and a hip bone.

9. The implant or scaffold of claim 8, wherein at least 95 percent of pores have a diameter of 1-500 microns.

10. The implant or scaffold of claim 1, comprising a substantially uniform cross-sectional morphology having a porosity of greater than about 35 percent, wherein the pores are interconnected and have an average diameter of 50-250 microns, and wherein said implant or scaffold has a compressive strength ASTM #D695 of from 10 to 200 megapascals (Mpa) and a flexural modulus ASTM #D570 of from 0.5 to 4.5 gigapascals (GPa).

11. The implant or scaffold of claim 10, comprising a bone replacement scaffolding for ongrowth/ingrowth of tissues, or as a support for stem cells.

12. An implant or scaffold comprising a laser sintered composition comprising pure poly(ether ketone ketone) (PEKK) the implant or scaffold not comprising calcium phosphate, wherein said powder has an average particle size of from 10-150 microns, and is either a) semi-crystalline, having at least 10% crystallinity by weight as measured by DSC, or said powder is b) quasi-amorphous, at most 2% crystallinity as measured by DSC.

13. The implant or scaffold of claim 10, comprising a three-dimensional lattice structure having a plurality of bars crossing each other in a plurality of zones, the bars being fused in each of the zones, wherein the interstitial spaces between adjacent bars define a plurality of interconnected pores or channels in the lattice structure.

14. An implant or scaffold comprising a laser sintered composition composed exclusively of pure poly(ether ketone ketone) (PEKK) powder, the implant or scaffold not comprising calcium phosphate, wherein said powder has an average particle size of from 10-150 microns, and is either a) semi-crystalline, having at least 10% crystallinity by weight as measured by DSC, or said powder is b) quasi-amorphous, at most 2% crystallinity as measured by DSC.

15. The laser sinterable composition of claim 12, wherein said composition further comprises one or more fillers selected from the group consisting of glass, carbon, mineral fillers, surface-bioactive ceramics, solids that will render the implant or scaffold radioopaque, and barium sulfate (BaSO.sub.4).

16. The laser sinterable composition of claim 14, wherein said powder has an average particle size of from 20-100 microns.

17. The laser sinterable composition of claim 14 wherein said semi-crystalline powder has 15-90% crystallinity as measured by DSC.

18. The laser sinterable composition of claim 14, wherein said powder has an average particle size of from 50-70 microns.

19. The laser sinterable composition of claim 14 wherein said semi-crystalline powder has 15-35% crystallinity as measured by DSC.

20. A process for producing a customized implant or scaffold for bone replacement comprising the steps of: (a) scanning a patient in an area requiring bone repair or replacement to obtain tomographic information; (b) designing a bone implant model using computer aided design from the tomographic information obtained from the patient; (c) optionally, modifying the bone implant model by one or more of the following steps: adding suture anchors, threaded holes, mating surfaces and textures, open cell regions for scaffolding, surface pores to carry antibiotics, and/or varying density or porosity levels so as to vary stiffness or rigidity; and (d) forming a bone implant or scaffold using a solid free-form fabrication method from the bone implant model, the bone implant being composed of sequential layers of biocompatible pure laser sintered poly(ether ketone ketone) (PEKK) powder, said implant or scaffold being capable of ongrowth/ingrowth of tissues said implant or scaffold not comprising calcium phosphate.

21. The process of claim 20, wherein said fabrication method in step (d) is by selective laser sintering (SLS).

22. The process of claim 20, wherein the PEKK powder has an average particle size of from 10 to 150 microns.

23. The process of claim 20, wherein said PEKK powder further comprises from 5 to 40 weight percent of additives, based on the weight of PEKK.

24. The process of claim 23, wherein said additives are selected from the group consisting of solids to render the implant or scaffold radioopaque.

25. The implant or scaffold of claim 1, wherein the implant or scaffold has openings to encourage bone, vascular, and nerve growth.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) Image based modeling involves three basic steps, namely, mage acquisition, image processing, and three dimensional reconstruction (3DR) to form voxels (basic unit of computed tomography reconstruction) that describe the 3D shape of the model for use in further and more advanced modeling, and subsequent manufacture.

(2) As noted above, raw patient data in the form of noninvasive images of the area encompassing the diseased or damaged bone(s) may be acquired from any number of medical diagnostic imaging systems such as CT, MRI, PET, and x-ray scans.

(3) Image processing and 3DR may be achieved using any suitable medical reconstructive and reverse engineering software such as MIMICS software programs for processing and editing images for medical and surgical applications, which are available from Materialise N.V. Technologielaan 15, B-3001, Leuven, Belgium, and GEOMAGIC STUDIO computer software for creating digitized models, which is available from Geomagic U.S., 3200 East Hwy 54, Cape Fear Building, Suite 300, Research Triangle Park, N.C., 27709.

(4) Once loaded into the software, the raw patient data in the form of noninvasive images (which are typically in the form of slice images) are properly registered and aligned. Next, the region of interest (i.e., the diseased or damaged bone(s)) is identified and a 3D rendering or model is made. In a first contemplated embodiment, the 3D model, which is in the form of segmented information, is further customized and then exported to an RP machine using, for example, an RP Slice Module, which interfaces with MIMICS software programs or GEOMAGIC STUDIO computer software and reportedly any kind of RP system. The RP Slice Module is available from Materialise N.V. In a second contemplated embodiment, the segmentation is transferred directly to an RP machine.

(5) The 3D rendering or model may be enhanced and further customized by, for example, converting the 3D voxel dataset that describes the 3D shape of the model to point data form, cleaning the points (i.e., eliminating noise points), triangulating the points to form a faceted model, varying density or porosity levels, adding open cell regions for scaffolding, modeling the bone surface using freeform surfaces or NURBS patches, further refining and enhancing the surface (e.g., adding surface pores to carry antibiotics, adding suture anchors and/or threaded holes, mating surfaces and textures), etc. Design software suitable for enhancing and further customizing the 3D rendering or model includes software available from SolidWorks Corporation, 300 Baker Avenue, Concord, Mass. 01742, under the trade designation SOLIDWORKS computer software.

(6) The thus generated CAD models are saved in an IGES or STEP/STL format, which are neutral data formats that allow for transfer of the 3D rendering or CAD model between dissimilar systems, and then exported to an RP machine.

(7) In a preferred embodiment, the RP machine is a powder-based SLS system. The system, which typically comprises two side powder cartridges, a platform with variable height, heaters and a laser source, produces 3D objects from sliced 3D CAD models using powdered materials with heat generated by the laser.

(8) Although the CAD-based RP process for the design and manufacture of these customized implants will be described herein mainly in connection with SLS, the invention is not so limited. Other RP-based manufacturing methods such as fused deposition modeling (FDM) and Selective Mask Sintering (SMS) may be used to manufacture the inventive implant.

(9) An SLS system suitable for use in the present invention comprises: (a) a powder delivery system, for applying successive layers of PEKK power onto a target surface on a variable height part bed or platform; (b) a laser for generating a laser beam; (c) a scanning system for controllably directing the laser beam to a target plane at an uppermost surface of the powder layer; and (d) a computer, coupled to the powder delivery system and scanning system, and programmed to perform a plurality of operations comprising: reading data from a CAD model, directing the powder delivery system to lay down successive layers of PEKK powder, and directing the scanning system to laser scan each such successive PEKK layer.

(10) Preferably, the laser for generating a laser beam in the SLS system is a carbon dioxide (CO.sub.2) laser source. Such SLS systems are available from EOS of North America Inc., 28970 Cabot Drive, Novi, Mich., 48377-2978, and from 3D Systems, 333 Three D Systems Circle, Rock Hill, S.C. 29730.

(11) PEKK is used in either its pure form or with fillers or additives selected from the group including, but not limited to, surface-bioactive ceramics (e.g., hydroxyapatite (HAp), BIOGLASS biologically active glass), resorbable bioactive ceramics (e.g., -tricalcium phosphate (-TCP), -TCP), and solids that will render the implant or scaffold radioopaque (e.g., barium sulfate (BaSO.sub.4)). Processing aids such as carbon black and aluminum powder are not employed in the subject invention.

(12) In a first preferred embodiment, PEKK powder with an average particle size ranging from about 10 to about 150 microns is used in its pure form. Such powders are available from Oxford Performance Materials, Inc., 120 Post Rd., Enfield, Conn. 06082 (Oxford Performance Materials), under the product designation OXPEKK-IG PEKK powder.

(13) In a second preferred embodiment, PEKK powder in the form of a compound resin powder with an average particle size ranging from about 10 to about 150 microns is used, the compound resin powder being prepared by melt blending a mixture of PEKK resin with from about 10 to about 40% by wt. of one or more fillers or additives (e.g., HAp, BIOGLASS biologically active glass, -TCP, -TCP, BaSO.sub.4) using conventional melt-blending techniques and then grinding the blended product to form a powder.

(14) In operation, the platform used in the SLS system is heated to a temperature ranging from about 280 C. to about 350 C. (preferably, from about 280 C. to about 295 C. (for quasi-amorphous PEKK) or from about 335 C. to about 350 C. (for semi-crystalline PEKK)), and a thin layer of PEKK powder having an average particle size ranging from about 10 to about 150 microns (preferably, from about 20 to about 100 microns) is spread evenly onto the heated platform with a roller mechanism. Then, the powder is raster-scanned with the CO.sub.2 laser beam (power density (energy per unit area and time)) ranging from about 0.015 to about 1.5 Wattsec/mm.sup.2 (preferably, from about 0.1 to about 0.25 Wattsec/mm.sup.2), with only the powder that is struck becoming fused. Successive layers of PEKK powder are then deposited and raster-scanned one on top of another until the implant or scaffold is complete. Each layer is sintered deeply enough to bond it to the underlying or preceding layer.

(15) The customized implants of the present invention demonstrate biomechanical properties similar (if not identical) to that of natural bone. More specifically, the inventive implants have a compressive strength (ASTM #D695) or load bearing capability ranging from about 10 to greater than about 200 megapascals (MPa). This compressive strength provides load-bearing capability greater than typical cancellous bone and up to that of typical cortical bone. The inventive implants also have a flexural modulus (ASTM #D570) ranging from about 0.5 to greater than about 4.5 gigapascals (GPa).

(16) For implants used to replace bone in load bearing applications such as the spine, long bone and hip, low porosity (i.e., less than about 10%) implants would be formed. These implants demonstrate compressive strength (ASTM #D695) or load bearing capability ranging from about 100 to greater than about 200 MPa and flexural modulus (ASTM #D570) ranging from about 3.5 to greater than about 4.5 GPa.

(17) In one contemplated embodiment, the surface topography of the low porosity implant is altered and/or one or more through openings are added to encourage bone, vascular and nerve in-growth. As will be readily appreciated by one skilled in the art, such alterations or additions may be designed into the CAD model, or formed post-manufacture by drilling, cutting, punching, or other suitable means.

(18) For implants used to replace bone in partially load bearing applications such as scaffolding for ongrowth/ingrowth of tissues, support for stem cell media and the like, a higher porosity implant (i.e., open cell-3D interconnected pores) would be formed. These implants demonstrate compressive strength (ASTM #D695) or load bearing capability ranging from about 10 to about 200 MPa and a flexural modulus (ASTM #D570) ranging from about 0.5 to about 4.5 GPa.

(19) In one contemplated embodiment, the higher porosity implant is in the form of a three-dimensional lattice structure. The lattice structure, which is optimized for bone, vascular and nerve in-growth, has a plurality of bars crossing each other in a plurality of zones, the bars being fused in each of these zones. Interstitial spaces provided between adjacent bars define a plurality of interconnected pores or channels in the lattice structure.

(20) The implant of the present invention may contain one or more porous reservoirs, which hold one or more therapeutic agents including, but not limited to, antibiotics, anti-coagulants, anti-inflammatory, anti-metabolites, antivirals, bone morphogenic proteins, cell adhesion molecules, growth factors, healing promotors, immunosuppressants, vascularizing agents, topical anesthetics/analgesics, and the like. These therapeutic agents may be prepared with carriers that will protect against rapid release (e.g., a controlled release vehicle such as a polymer, microencapsulated delivery system or bioadhesive gel). In one contemplated embodiment, the therapeutic agent is encapsulated by biocompatible, degradable polymers including, but not limited to, polyhydroxy adds such as polylactic add (PLA), polyglycolic add (PGA), and their copolymers (ALGA). These polymers are degraded by hydrolysis to products that can be metabolized and excreted.

(21) The inventive implant may also be modified to include means for securing the implant to adjacent bony structures. For example, interfacial fastening mechanisms such as custom mating screws and fasteners may be designed into the CAD model, or formed/affixed post-manufacture.

(22) While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not limitation. Thus, the breadth and scope of the present invention should not be limited by any of the exemplary embodiments.