Complex three-dimensional composite scaffold resistant to delimination

• US 20030114936A1
• Filed: 07/29/2002
• Published: 06/19/2003
• Est. Priority Date: 10/12/1998
• Status: Abandoned Application

• Current Assignee: Therics Inc.
• Original Assignee: Therics Inc.
• Inventors: Sherwood, Jill K., Gaylo, Christopher M., Monkhouse, Donald
• Application Number:
  US10/207,531
• Publication Number:
  US 20030114936A1
• Time in Patent Office: Days
• US Class Current: 623/23.58
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2/30942 for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
• CPC Class Codes: A61F 2/468 Testing instruments for artificial joints for testing non-implantable prostheses A61F2/76
• CPC Class Codes: A61F 2002/0086 for preferentially controlling or promoting the growth of specific types of cells or tissues of bone tissue onto implantable joints A61F2002/3093
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/2835 Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
• CPC Class Codes: A61F 2002/30004 the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
• CPC Class Codes: A61F 2002/30011 differing in porosity
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30199 Three-dimensional shapes
• CPC Class Codes: A61F 2002/30301 saddle-shaped
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/30762 Means for culturing cartilage
• CPC Class Codes: A61F 2002/30766 Scaffolds for cartilage ingrowth and regeneration
• CPC Class Codes: A61F 2002/3093 for promoting ingrowth of bone tissue
• CPC Class Codes: A61F 2002/30952 using CAD-CAM techniques or NC-techniques
• CPC Class Codes: A61F 2002/30962 using stereolithography
• CPC Class Codes: A61F 2002/30968 Sintering
• CPC Class Codes: A61F 2002/3097 : using laser
• CPC Class Codes: A61F 2002/30971 : Laminates, i.e. layered products
• CPC Class Codes: A61F 2002/4648 : Means for culturing bone graft
• CPC Class Codes: A61F 2210/0004 : bioabsorbable
• CPC Class Codes: A61F 2230/0063 : Three-dimensional shapes
• CPC Class Codes: A61F 2230/0095 : Saddle-shaped
• CPC Class Codes: A61F 2240/001 : Designing or manufacturing processes
• CPC Class Codes: A61F 2250/0014 : having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
• CPC Class Codes: A61F 2250/0023 : differing in porosity
• CPC Class Codes: A61F 2310/00179 : Ceramics or ceramic-like structures
• CPC Class Codes: A61F 2310/00203 : containing alumina or aluminium oxide
• CPC Class Codes: A61F 2310/00293 : containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61F 2310/00365 : Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 27/46 : with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: B29C 64/165 : using a combination of solid and fluid materials, e.g. a powder selectively bound by a liquid binder, catalyst, inhibitor or energy absorber
• CPC Class Codes: B29L 2031/7532 : Artificial members, protheses

Abstract

The devices disclosed herein are composite implantable devices having a gradient of one or more of the following: materials, macroarchitecture, microarchitecture, or mechanical properties, which can be used to select or promote attachment of specific cell types on and in the devices prior to and/or after implantation. In preferred embodiments, the implants include complex three-dimensional structure, including curved regions and saddle-shaped areas. In various embodiments, the gradient forms a transition zone in the device from a region composed of materials or having properties best suited for one type of tissue to a region composed of materials or having properties suited for a different type of tissue. Methods to improve these devices for use in repair or replacement of cartilage and/or bone have been developed, which specifically address 1) the selection of the appropriate polymeric material for the cartilage region, 2) mechanical testing of the bone region including the effect of porosity and polymer/calcium phosphate ratio, and 3) prevention of delamination in the transition region.

Claims

1. A composite medical implant comprising

multiple regions having a different composition, the regions comprising a combination of structure and chemical composition varying from one region to another region to prevent delamination and to promote cell seeding, cell attachment, cell ingrowth or differentiation of cells when implanted into a patient.

2. The implant of claim 1 wherein the implant comprises a curved surface.

3. The implant of claim 2 wherein the implant comprises a curved surface which is curved in more than one orthogonal direction.

4. The implant of claim 2 wherein at least one of the regions comprises a curved boundary with another region.

5. The implant of claim 4 wherein the curved boundary is curved in more than one orthogonal direction.

6. The implant of claim 1 comprising one or more gradients from one region to another region.

7. The implant of claim 6 wherein the gradient is of structure.

8. The implant of claim 6 wherein the gradient is of composition.

9. The implant of claim 7 wherein the structure is porosity.

10. The implant of claim 7 wherein the gradient is of pore size.

11. The implant of claim 1 wherein the implant is a bone-cartilage implant including bone forming and cartilage forming regions comprising

a gradient of materials and porosity between the bone forming and the cartilage forming regions.

12. The implant of claim 11 comprising

a bone forming region having a porosity of approximately 45-65% and

a cartilage forming region having a porosity of approximately 90%.

13. The implant of claim 11 comprising an interconnected region having a minimum of 32% porosity.

14. The implant of claim 11 having a pore size of greater than 100 microns in the bone forming region.

15. The implant of claim 11 wherein the bone forming region comprises a cloverleaf shape.

16. The implant of claim 11 comprising osteoconductive and/or osteoinductive agents.

17. The implant of claim 16 wherein the osteoconductive material is selected from the group consisting of hydroxyapatite, calcium-phosphorus compounds, bone and demineralized bone matrix.

18. The implant of claim 1 formed by solid free form fabrication.

19. The implant of claim 18 formed by three dimensional printing.

20. The implant of claim 1 further comprising one or more agents selected from the group consisting of growth stimulating or differentiating factors and imaging agents.

21. A method to reduce delamination between regions of an implant comprising one or more of the following steps selected from the group consisting of

selecting a polymer optimized to degrade at a controlled rate;

forming a scaffold containing leachable particulate;

forming the scaffold with macroscopic channels;

removing residual solvent; and

leaching at room temperature;

wherein the implant contains regions having a composition and porosity selected to avoid delamination due to shrinkage.

22. The method of claim 21 comprising removing residual solvent using liquid or supercritical carbon dioxide.

23. A method of repairing or replacing tissue comprising implanting into a patient a composite medical implant comprising multiple regions having a different composition, the regions comprising a combination of structure and chemical composition varying from one region to another region to prevent delamination and to promote cell seeding, cell attachment, cell ingrowth or differentiation of cells when implanted into a patient.

24. The method of claim 23 wherein the tissue is bone.

25. The method of claim 23 wherein the tissue is bone and cartilage.

26. The method of claim 23 wherein the implant is seeded by placing the implant in a suspension of cells wherein the cells attach to sites on the implant based on the porosity at the sites.

27. The method of claim 23 wherein the porosity is at least 85%.

28. The method of claim 23 wherein the pores are 125 microns or greater for seeding of cells for forming bone.

29. A method of making a composite implant, comprising:

depositing a layer of powder comprising non-leaching solid particles and porogen particles, wherein the composition of the non-leaching solid particles or the proportion between non-leaching solid particles and the porogen particles can vary from place to place within the layer;

depositing onto the layer of powder in selected places a binder liquid suitable to bind the particles together;

allowing or causing the binder liquid to at least partially dry;

repeating the above steps as many times as desired to form a three-dimensional object;

separating the three-dimensional object from unbound powder particles; and

leaching the porogen from the resulting object by dissolving the porogen in a solvent which dissolves the porogen but not the non-leaching solid particles.

30. The method of claim 29 wherein the non-leaching solid particles comprise one or more substances selected from the group consisting of:

resorbable polymers, nonresorbable polymers, hydroxyapatite, tricalcium phosphate, other calcium-phosphorus compounds, other ceramics, bone particles, and demineralized bone matrix.

31. The method of claim 29 wherein the porogen is soluble in water.

32. The method of claim 31 wherein the porogen comprises a water soluble salt or sugar.

33. The method of claim 29 wherein the layer of powder is deposited by dispensing a slurry or suspension comprising the non-leaching solid particles and the porogen particles in a carrier liquid, the proportion between the solid non-leaching particles and the porogen particles in the suspension being variable from one place to another in the layer of powder.

34. The method of claim 29 wherein the depositing is performed by a single dispenser.

35. The method of claim 29 wherein the depositing is performed by more than one dispenser.

36. The method of claim 29 wherein the dispensing is performed by one or more piezoelectric dispensers.

37. The method of claim 29 wherein the dispensing is performed by one or more microvalve dispensers.

38. The method of claim 29 wherein the layer of powder comprises at least two regions, each region having its own composition of powder.

39. The method of claim 29 comprising spreading a non-uniform composition powder within a layer using a roller to deposit the powder.

40. The method of claim 29 wherein the powder is deposited as a slurry or suspension.

41. The method of claim 40 comprising depositing one or more slurries or suspensions at least one of which comprises non-leaching solid particles and the porogen particles.