Device and methods for in vivo culturing of diverse tissue cells

• US 5,981,825 A
• Filed: 05/13/1994
• Issued: 11/09/1999
• Est. Priority Date: 05/13/1994
• Status: Expired due to Term

• Current Assignee: Kensey Nash Corporation (DSM-Firmenich AG)
• Original Assignee: THM Biomedical, Inc. (DSM-Firmenich AG)
• Inventors: Brekke, John H.
• Primary Examiner(s): Clarke, Robert A.
• Application Number:
  US08/242,557
• Time in Patent Office: 2,006 Days
• Field of Search: 623/11, 623/16, 623/20, 435/240, 435/243, 435/240.2, 422/426
• US Class Current: 623/11.11
• 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 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: C08L 5/04 Alginic acid; Derivatives thereof

Abstract

An anatomically specific, bioresorbable, implant device for facilitating the healing of voids in bone, cartilage and soft tissue is disclosed. A preferred embodiment of using the implant device for facilitating the healing of a human joint lesion includes a cartilage region invested with an alginate microstructure joined with a subchondral bone region invested with a hyaluronan microstructure. The alginate selectively dispersed in the cartilage region enhances the environment for chondrocytes to grow articular cartilage. The hyaluronan selectively dispersed in the subchondral bone region enhances the environment for mesenchymal cells which migrate into that region'"'"'s macrostructure and which differentiate into osteoblasts. The microstructures can be invested at varying concentrations in the regions. A hydrophobic barrier, strategically positioned within the subchondral bone region macrostructure, shields the chondrocytes from the oxygenated blood in subchondral cancellous bone. In the preferred form, the cartilage region includes a tangential zone including a network of intercommunicating void spaces having a horizontal orientation and in communication with synovial fluid and includes a radial zone including multiple void spaces oriented in both horizontal and vertical planes and providing intercommunication between the tangential zone and the subchondral bone region.

Claims

1. An anatomically specific device for regenerating at least first and second, juxtaposed tissues having different histologic patterns, prior to implantation, comprising, in combination:

a first region having an internal three-dimensional architecture to approximate the histologic pattern of the first tissue; and

a second region having an internal three-dimensional architecture to approximate the histologic pattern of the second tissue, with the first and second regions being integrally connected together at an interface without the use of solvents or chemical reactions between the first and second regions, with the regions being formed of a bioresorbable polymer.

2. The anatomically specific device of claim 1 wherein each of the first and second regions include a macrostructure defining void spaces, with the device further comprising, in combination:

at least a first material for enhancing the attachment of cells to the three-dimensional architecture in the void spaces of at least one of the first and second regions.

3. The anatomically specific device of claim 2 wherein the cell attachment enhancing material is present at varying concentrations in the regions.

4. The anatomically specific device of claim 2 further comprising, in combination:

a second material for enhancing the attachment of cells to the three-dimensional architecture in the void spaces of the second region with the first region being substantially free of the second cell attachment enhancing material, with the first cell attachment enhancing material located in the void spaces of the first region and the second region being substantially free of the first cell attachment enhancing material.

5. The anatomically specific device of claim 1 wherein the first region is divided into first and second zones having differing three-dimensional patterns, with the second zone located between the first zone and the second region.

6. The anatomically specific device of claim 5 wherein the three-dimensional pattern of the first zone includes a network of intercommunicating voids which have an orientation parallel to the interface surface, and the three-dimensional pattern of the second zone includes a network of inter-communicating voids extending between the first zone and the second region.

7. The anatomically specific device of claim 6 further comprising, in combination:

a porous microstructure formed from a material for enhancing the attachment of cells to the three-dimensional architecture and located in the intercommunication voids of the first region and carried by and separate from the bioresorbable polymer forming the first region.

8. The anatomically specific device of claim 7 wherein the cell attachment enhancing material is alginate.

9. The anatomically specific device of claim 8 wherein the first tissue is cartilage and the second tissue is subchondral cancellous bone;

and wherein the device further comprises, in combination;

RGD attachment moiety of fibronectin carried by the cell attachment enhancing material and within the intercommunicating voids of the first region.

10. The anatomically specific device of claim 9 wherein the second region includes a porous macrostructure including interconnecting voids;

and wherein the device includes a material for enhancing the attachment of cells to the three-dimensional architecture located in the interconnecting voids of the porous macrostructure and carried by and separate from the bioresorbable polymer forming the porous macrostructure.

11. The anatomically specific device of claim 10 wherein the cell attachment enhancing material of the porous macrostructure is a chemotactic ground substance in the form of hyaluronic acid.

12. The anatomically specific device of claim 1 wherein the first and second regions include intercommunicating voids;

and wherein the device further comprises, in combination;

at least one hydrophobic barrier within the three-dimensional architecture of at least one of the first and second regions, with the second region outside of the hydrophobic barrier being hydrophilic.

13. The anatomically specific device of claim 12 wherein the first and second regions are formed by a single bioresorbable polymer, with the single bioresorbable polymer of the first region being hydrophobic and the second region being hydrophilic by treatment with a surfactant.

14. The anatomically specific device of claim 12 wherein the hydrophobic barrier is spaced from the interface surface.

15. The anatomically specific device of claim 14 wherein the hydrophobic barrier begins in the second region about 500 to 800 micrometers from the interface surface.

16. The anatomically specific device of claim 15 wherein the first tissue is cartilage and the second tissue is subchondral cancellous bone.

17. A bioresorbable polymer device for regenerating cartilage tissue interfacing at an interface with subchondral cancellous bone and located between the subchondral cancellous bone and synovial fluid, prior to implantation, comprising, in combination:

a tangential zone including a network of intercommunicating void spaces having an orientation parallel to the interface and in communication with the synovial fluid; and

a radial zone located between the tangential zone and the interface, with the radial zone including void spaces extending between and providing communication between the interface and the tangential zone.

18. The bioresorbable device of claim 17 wherein the tangential zone includes channels extending parallel to the interface and formed by major polymer strands running parallel to each other, with the channels separated by a network of minor polymer strands extending parallel to the interface and generally perpendicular to the major polymer strands.

19. The bioresorbable device of claim 18 wherein the radial zone includes thin sheets of the bioresorbable polymer arranged perpendicular to the interface.

20. The bioresorbable device of claim 17 further comprising, in combination:

a porous microstructure formed from a material for enhancing the attachment of cells to the three-dimensional architecture and located in the void spaces of at least one of the tangential and radial zones and carried by and separate from the bioresorbable polymer defining the void spaces.

21. The bioresorbable device of claim 20 wherein the cell attachment enhancing material is alginate.

22. The bioresorbable device of claim 21 further comprising, in combination:

RGD attachment moiety of fibronectin carried by the cell attachment enhancing material and within the void spaces.

23. The bioresorbable device of claim 20 wherein the cell attachment enhancing material is present at varying concentrations in the zones.

24. The bioresorbable device of claim 17 further comprising, in combination:

means for protecting the tangential and radial zones from intimate contact with collateral circulation from the subchondral cancellous bone.

25. The bioresorbable device of claim 24 wherein the protecting means comprises a hydrophobic barrier at the interface with the radial zone.

26. A bioresorbable device for facilitating healing of voids in tissue comprising, in combination:

a macrostructure made from a polymer providing an internal three-dimensional architecture defining a network of void spaces; and

a material for enhancing the attachment of cells to the three-dimensional architecture carried by the macrostructure at varying concentrations in the void spaces of the three-dimensional architecture.

27. The bioresorbable device of claim 26 wherein the macrostructure includes first and second, spaced surfaces, with the concentration of the cell attachment enhancing material carried by the macrostructure decreasing from the first surface to the second surface.

28. The bioresorbable device of claim 27 wherein the cell attachment enhancing material forms a porous microstructure located in the intercornecting voids and carried by and separate from the polymer forming the macrostructure.

29. A bioresorbable device for facilitating healing of voids in tissue, prior to implantation, comprising, in combination:

a structure made from a polymer providing an internal three-dimensional architecture including at least first and second locations; and

a first material for enhancing the attachment of cells to the three-dimensional architecture carried by the structure in the first location, with the second location being substantially free of the first cell attachment enhancing material.

30. The bioresorbable device of claim 29 further comprising, in combination:

a second material for enhancing the attachment of cells to the three-dimensional architecture carried by the structure in the second location, with the first location being substantially free of the second cell attachment enhancing material.

31. The bioresorbable device of claim 30 wherein the first cell attachment enhancing material facilitates osteoneogenesis and the second cell attachment enhancing material facilitates chondroneogenesis.

32. The bioresorbable device of claim 31 wherein the first cell attachment enhancing material comprises a chemotactic ground substance in the form of hyaluronic acid and the second cell attachment enhancing material comprises alginate.

33. The bioresorbable device of claim 31 further comprising, in combination:

RGD attachment moiety of fibronectin carried by the second cell attachment enhancing material.

34. The bioresorbable device of claim 33 wherein the structure is in the form of a porous macrostructure including interconnecting voids;

and wherein the cell attachment enhancing materials form porous microstructures located in the interconnecting voids of the respective locations and carried by and separate from the polymer forming the porous macrostructure.

35. A bioresorbable device for facilitating healing of voids in tissue, prior to implantation, comprising, in combination:

a structure made from a polymer providing an internal three-dimensional architecture approximating a first tissue; and

a barrier positioned within the three-dimensional architecture of the structure for prohibiting water-based fluid from passing therethrough;

wherein the barrier is hydrophobic and the three-dimensional architecture outside of the barrier is hydrophilic on at least one surface.

36. The bioresorbable device of claim 35 wherein the polymer is hydrophobic and is treated with a surfactant to become hydrophilic.

37. The bioresorbable device of claim 35 wherein the internal three-dimensional architecture approximates a histologic pattern of the first tissue.

38. A method comprising the steps of:

providing a structure made from a bioresorbable polymer and having an internal three-dimensional architecture including at least first and second locations;

providing a first material for enhancing the attachment of cells to the three-dimensional architecture; and

investing the first location with the first cell attachment enhancing material while the second location is substantially free of the first cell attachment enhancing material.

39. The method of claim 38 wherein the providing step comprises the steps of:

providing the first location;

providing the second location separate from the first location; and

joining the first and second locations to form the structure; and

wherein the investing step comprises the step of investing the first location with the first cell attachment enhancing material prior to the joining step.

40. The method of claim 39 wherein the structure includes first and second, spaced surfaces, with the first surface located on the first location and the second surface located on the second location;

and wherein the investing step comprises investing the first location through the first surface with a volume of the cell attachment enhancing material less than or equal to the volume of cell attachment enhancing material which could be carried by the first location.

41. The method of claim 38 further comprising the steps of:

providing a second material for enhancing the attachment of cells to the three-dimensional architecture; and

investing the second location with the second cell attachment enhancing material while the first location is substantially free of the second cell attachment enhancing material.

42. A bioresorbable polymer device for regenerating cartilage tissue interfacing at an interface with subchondral cancellous bone and located between the subchondral cancellous bone and synovial fluid, prior to implantation, comprising, in combination:

a cartilage region having an internal three-dimensional architecture to approximate the histologic pattern of the cartilage tissue;

a subchondral bone region having an internal three-dimensional architecture to approximate the histologic pattern of the subchondral cancellous bone, with the cartilage and subchondral bone regions being integrally connected together at an interface surface, with the regions being formed of a bioresorbable polymer, with the cartilage region being divided into a tangential zone including a network of intercommunicating void spaces having an orientation parallel to the interface surface and in communication with the synovial fluid and a radial zone located between the tangential zone and the interface surface, with the radial zone including void spaces extending between and providing communication between the interface surface and the tangential zone;

a material for enhancing the attachment of cells to the three-dimensional architecture at varying concentrations in the cartilage region, with the subchondral bone region being substantially free of the cell attachment enhancing material; and

a barrier formed between the cartilage and subchondral bone regions for prohibiting water-based fluid from passing therethrough.