Biocompatible scaffolds with tissue fragments

• US 20040078090A1
• Filed: 02/25/2003
• Published: 04/22/2004
• Est. Priority Date: 10/18/2002
• Status: Abandoned Application

• Current Assignee: Depuy Mitek LLC (Johnson & Johnson)
• Original Assignee: Depuy Mitek LLC (Johnson & Johnson)
• Inventors: Binette, Francois, Hwang, Julia, Gosiewska, Anna, Dhanaraj, Sridevi
• Application Number:
  US10/374,772
• Publication Number:
  US 20040078090A1
• Time in Patent Office: Days
• US Class Current: 623/23.76
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2/08 Muscles; Tendons; Ligaments sutures A61B17/04
• CPC Class Codes: A61F 2310/0097 Coating or prosthesis-covering structure made of pharmaceutical products, e.g. antibiotics
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 2430/10 for reconstruction of tendons or ligaments
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/36 containing ingredients of undetermined constitution or reaction products thereof , e.g. transplant tissue, natural bone, extracellular matrix isolated natural compounds, e.g. collagen A61L27/24
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3612 Cartilage, synovial fluid
• CPC Class Codes: A61L 27/3616 Blood, e.g. platelet-rich plasma
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage

Abstract

A biocompatible tissue repair implant or scaffold device is provided for use in repairing a variety of tissue injuries, particularly injuries to cartilage, ligaments, tendons, and nerves. The repair procedures may be conducted with implants that contain a biological component that assists in healing or tissue repair. The biocompatible tissue repair implants include a biocompatible scaffold and particles of living tissue, such that the tissue and the scaffold become associated. The particles of living tissue contain one or more viable cells that can migrate from the tissue and populate the scaffold.

Claims

1. A biocompatible implant, comprising:

a biocompatible scaffold; and

at least one tissue fragment that is associated with at least a portion of the scaffold, wherein the tissue fragment includes an effective amount of viable cells that can migrate out of the tissue fragment and populate the scaffold.

2. The implant of claim 1, wherein the scaffold comprises a synthetic polymer, a natural polymer, an injectable gel, a ceramic material, autogeneic tissue, allogeneic tissue, xenogeneic tissue and combinations thereof.

3. The implant of claim 1, wherein the at least one tissue fragment includes a plurality of cells and, upon implantation at a surgical site, at least a portion of the plurality of cells is able to migrate out of the tissue fragment associated with the scaffold to proliferate and integrate with surrounding tissue at a site of implantation.

4. The implant of claim 1, wherein the at least one tissue fragment includes a plurality of cells and, prior to implantation at a surgical site, at least a portion of the plurality of cells is able to migrate out of the tissue fragment associated with the scaffold to proliferate and populate the scaffold.

5. The implant of claim 1, wherein the biocompatible scaffold further comprises an adhesion agent for anchoring the suspension of tissue fragment to the biocompatible scaffold.

6. The implant of claim 5, wherein the adhesion agent comprises an anchoring agent selected from the group consisting of hyaluronic acid, fibrin glue, fibrin clot, collagen gel, gelatin-resorcin-formalin adhesive, mussel-based adhesive, dihydroxyphenylalanine (DOPA) based adhesive, chitosan, transglutaminase, poly(amino acid)-based adhesive, cellulose-based adhesive, synthetic acrylate-based adhesives, platelet rich plasma (PRP), Matrigel, Monostearoyl Glycerol co-Succinate (MGSA), Monostearoyl Glycerol co-Succinate/polyethylene glycol (MGSA/PEG) copolymers, laminin, elastin, proteoglycans and combinations thereof.

7. The implant of claim 5, wherein the adhesion agent comprises a chemical cross-linking agent selected from the group consisting of divinyl sulfone (DVS), polyethylene glycon divinyl sulfone (VS-PEG-VS), hydroxyethyl methacrylate divinyl sulfone (HEMA-DIS-HEMA), formaldehyde, glutaraldehyde, aldehydes, isocyanates, alkyl and aryl halides, imidoesters, N-substituted maleimides, acylating compounds, carbodiimide, hydroxychloride, N-hydroxysuccinimide, light, pH, temperature, and combinations thereof.

8. The implant of claim 1, wherein the at least one tissue fragment comprises tissue selected from the group consisting of cartilage tissue, meniscal tissue, ligament tissue, tendon tissue, skin tissue, muscle tissue, periosteal tissue, pericardial tissue, synovial tissue, nerve tissue, kidney tissue, bone marrow, liver tissue, bladder tissue, pancreas tissue, spleen tissue, intervertebral disc tissue, embryonic tissue, periodontal tissue, vascular tissue and combinations thereof.

9. The implant of claim 8, wherein the at least one tissue fragment comprises autogeneic tissue, allogeneic tissue, xenogeneic tissue, and combinations thereof.

10. The implant of claim 1, where in the at least one tissue fragment comprises a bone-free tissue type selected from the group consisting of cartilage, meniscus, tendon, ligament and combinations thereof.

11. The implant of claim 1, wherein the biocompatible scaffold comprises a bioabsorbable material.

12. The implant of claim 2, wherein the biocompatible scaffold comprises a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), poly(propylene fumarate), copoly(ether-esters), polyalkylene oxalates, polyamides, tyrosine-derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, polyurethanes, biosynthetic polymers and combinations thereof.

13. The implant of claim 12, wherein the biocompatible scaffold comprises an aliphatic polyester selected from the group consisting of homopolymers or copolymers of lactides;

glycolides;

ε

-caprolactone;

hydroxybuterate;

hydroxyvalerate;

1,4-dioxepan-2-one;

1,5,8,12-tetraoxyacyclotetradecane-7,14-dione;

1,5-dioxepan-2-one;

6,6-dimethyl-1,4-dioxan-2-one;

2,5-diketomorpholine;

p-dioxanone (1,4-dioxan-2-one);

trimethylene carbonate (1,3-dioxan-2-one);

alkyl derivatives of trimethylene carbonate;

δ

-valerolactone;

β

-butyrolactone;

γ

-butyrolactone, ε

-decalactone, pivalolactone, α

,α

-diethylpropiolactone, ethylene carbonate, ethylene oxalate;

3-methyl-1,4-dioxane-2,5-dione;

3,3-diethyl-1,4-dioxan-2,5-dione;

6,8-dioxabicycloctane-7-one; and

combinations thereof.

14. The implant of claim 2, wherein the biocompatible scaffold comprises a natural polymer selected from the group consisting of a fibrin-based material, a collagen-based material, a hyaluronic acid-based material, a cellulose-based material, silk and combinations thereof.

15. The implant of claim 2, wherein the biocompatible scaffold comprises a ceramic material selected from the group consisting of hydroxyapatite, α

-tricalcium phosphate, β

-tricalcium phosphate, bioglass, calcium phospate, calcium carbonate, calcium sulfate, allograft bone graft material, xenograft bone graft material and combinations thereof.

16. The implant of claim 1, wherein the biocompatible scaffold comprises a polymeric foam component having pores with an open cell pore structure.

17. The implant of claim 16, wherein the biocompatible scaffold further comprises a reinforcing component formed of a biocompatible mesh-containing material.

18. The implant of claim 17, wherein the foam component is integrated with the reinforcing component such that the pores of the foam component penetrate the mesh of the reinforcing component and interlock with the reinforcing component.

19. The implant of claim 1, wherein the biocompatible scaffold further comprises at least one additional biological component applied thereto.

20. The implant of claim 19, wherein the at least one additional biological component comprises growth factors, matrix proteins, peptides, antibodies, enzymes, cytokines, viruses, nucleic acids, peptides, isolated cells, platelets or combinations thereof.

21. The implant of claim 1, wherein the at least one tissue fragment has a particle size in the range of about 0.1 to 2 mm³.

22. The implant of claim 1, wherein the at least one tissue fragment is added to a physiological buffering solution to form a suspension having a concentration of tissue fragments in the range of about 1 to 100 mg/cm².

23. The implant of claim 1, wherein the biocompatible implant further comprises at least one additional biocompatible scaffold selected from the group consisting of a synthetic polymer, a natural polymer, a ceramic material, autogeneic tissue, allogeneic tissue, xenogeneic tissue and combinations thereof, the at least one additional biocompatible scaffold being placed in contact with the at least one tissue fragment, such that at least a portion of the at least one tissue fragment is disposed between at least two biocompatible scaffolds.

24. A biocompatible implant, comprising:

a biocompatible scaffold;

a suspension having at least one cartilage tissue fragment that is associated with at least a portion of the scaffold, wherein the at least one tissue fragment in the suspension includes an effective amount of viable cells that can migrate out of the tissue fragment and populate the scaffold; and

a retaining element,

wherein at least a portion of the at least one tissue fragment is disposed between the biocompatible scaffold and the retaining element.

25. The implant of claim 24, wherein the scaffold comprises a synthetic polymer, a natural polymer, an injectable gel, a ceramic material, autogeneic tissue, allogeneic tissue, xenogeneic tissue, and combinations thereof.

26. The implant of claim 24, wherein the retaining element comprises allograft tissue selected from the group consisting of periosteum, perichondrium, fascia lata, semitendinosis tendon, gracilis tendon, dura, mesenthera, small intestine submucosa, skin dermis and combinations thereof.

27. The implant of claim 24, wherein the retaining element is selected from the group consisting of autogeneic tissue, allogeneic tissue, xenogeneic tissue, a hemostatic material, at least one additional biocompatible scaffold and combinations thereof

28. A kit for repairing a tissue injury, comprising:

a sterile container having one or more biocompatible scaffolds; and

a harvesting tool for collecting at least one viable tissue sample from a subject.

29. The kit of claim 28, further comprising at least one reagent for sustaining the viability of the at least one tissue sample.

30. The kit of claim 28, wherein the scaffold is selected from the group consisting of a synthetic polymer, a natural polymer, an injectable gel, a ceramic material, autogeneic tissue, allogeneic tissue, xenogeneic tissue, and combinations thereof.

31. The kit of claim 28, wherein the harvesting tool further comprises a processing tool for dividing the tissue sample, under sterile conditions, into at least one tissue fragment.

32. The kit of claim 28, wherein the biocompatible scaffold comprises an adhesion agent for anchoring the tissue sample to the biocompatible scaffold.

33. The kit of claim 32, wherein the adhesion agent comprises an anchoring agent selected from the group consisting of hyaluronic acid, fibrin glue, fibrin clot, collagen gel, alginate gel, gelatin-resorcin-formalin adhesive, mussel-based adhesive, dihydroxyphenylalanine (DOPA) based adhesive, chitosan, transglutaminase, poly(amino acid)-based adhesive, cellulose-based adhesive, synthetic acrylate-based adhesives, platelet rich plasma (PRP), Matrigel, Monostearoyl Glycerol co-Succinate (MGSA), Monostearoyl Glycerol co-Succinate/polyethylene glycol (MGSA/PEG), copolymers, laminin, elastin, proteoglycans and combinations thereof.

34. The kit of claim 32, wherein the adhesion agent comprises a cross-linking agent selected from the group consisting of divinyl sulfone (DVS), polyethylene glycon divinyl sulfone (VS-PEG-VS), hydroxyethyl methacrylate divinyl sulfone (HEMA-DIS-HEMA), formaldehyde, glutaraldehyde, aldehydes, isocyanates, alkyl and aryl halides, imidoesters, N-substituted maleimides, acylating compounds, carbodiimide, hydroxychloride, N-hydroxysuccinimide, light, pH, temperature, and combinations thereof.

35. The kit of claim 28, wherein the at least one reagent comprises a physiological solution selected from the group consisting of saline, phosphate buffer solution, Hank'"'"'s balanced salts, tissue culture medium, tissue culture medium including serum and combinations thereof.

36. A method of treating living tissue, comprising:

providing a biocompatible scaffold;

providing a sample of tissue in the form of finely divided tissue fragments;

depositing the sample of tissue upon the biocompatible scaffold to form a tissue implant; and

implanting the tissue implant in a desired position relative to the tissue to be treated.

37. The method of claim 36, wherein the biocompatible scaffold comprises a synthetic polymer, a natural polymer, an injectable gel, a ceramic material, autogeneic tissue, allogeneic tissue, xenogeneic tissue, and combinations thereof.

38. The method of claim 36, further comprising the step of affixing the tissue implant in the desired position relative to the tissue to be treated.

39. The method of claim 38, wherein the tissue implant is affixed in the desired position by applying a fastener to the tissue implant.

40. The method of claim 39, wherein the fastener comprises one or more sutures, one or more staples, one or more suture anchors, one or more tissue tacks, one or more darts, one or more screws, one or more pins, one or more arrows, fibrin glue, one or more fibrin clots, one or more biocompatible adhesives or combinations thereof.

41. The method of claim 36, wherein prior to the step of placing the tissue implant in the desired position relative to the tissue to be treated, the method further includes the step of incubating the tissue implant for a duration and under conditions effective to allow cells within the sample of tissue to populate the scaffold prior to reimplantation.

42. The method of claim 41, wherein the scaffold and associated finely divided tissue fragments are incubated for a duration in the range of about 7 days to 6 weeks.

43. The method of claim 41, wherein the scaffold and associated finely divided tissue fragments are incubated at a temperature in the range of about 20 to 40°

C. and in an atmosphere having a high humidity.

44. The method of claim 36, wherein the finely divided tissue fragments comprise tissue selected from the group consisting of cartilage tissue, meniscal tissue, ligament tissue, tendon tissue, skin tissue, muscle tissue, periosteal tissue, pericardial tissue, synovial tissue, nerve tissue, kidney tissue, bone marrow, liver tissue, bladder tissue, pancreas tissue, spleen tissue, and combinations thereof.

45. The method of claim 44, wherein the finely divided tissue fragments comprise autogeneic tissue, allogeneic tissue, xenogeneic tissue, and combinations thereof.

46. The implant of claim 36, where in the finely divided tissue fragments comprise a bone-free tissue type selected from the group consisting of cartilage, meniscus, tendon, ligament and combinations thereof.

47. The method of claim 36, wherein the finely divided tissue fragments associated with the biocompatible scaffold comprise a type that is the same as the tissue to be treated.

48. The method of claim 36, wherein the finely divided tissue fragments associated with the biocompatible scaffold comprise a type that is different from the tissue to be treated.

49. The method of claim 36, wherein the finely divided tissue fragments include an effective amount of viable cells that can migrate out of the tissue particles.

50. The method of claim 49, wherein the effective amount of cells migrate out of the tissue particles and populate an outer surface of the biocompatible scaffold.

51. The method of claim 49, wherein the effective amount of cells migrate out of the tissue particles and populate at least a portion of an interior region of the scaffold, such that the cells are embedded within the scaffold.

52. The method of claim 36, wherein the method further comprises, prior to placing the tissue implant in the desired position relative to the tissue to be treated, the additional step of providing at least one additional biocompatible scaffold and placing the at least one additional biocompatible scaffold over the deposited finely divided tissue fragments, such that at least a portion of the finely divided tissue fragments is disposed between at least two biocompatible scaffolds.

53. The method of claim 36, wherein the biocompatible scaffold further comprises an adhesion agent for anchoring the sample of living tissue to the biocompatible scaffold.

54. The method of claim 53, wherein the adhesion agent comprises an anchoring agent selected from the group consisting of hyaluronic acid, fibrin glue, fibrin clot, collagen gel, alginate gel, gelatin-resorcin-formalin adhesive, mussel-based adhesive, dihydroxyphenylalanine (DOPA) based adhesive, chitosan, transglutaminase, poly(amino acid)-based adhesive, cellulose-based adhesive, synthetic acrylate-based adhesives, platelet rich plasma (PRP), Matrigel, Monostearoyl Glycerol co-Succinate (MGSA), Monostearoyl Glycerol co-Succinate/polyethylene glycol (MGSA/PEG) copolymers, laminin, elastin, proteoglycans and combinations thereof.

55. The method of claim 53, wherein the adhesion agent comprises a cross-linking agent selected from the group consisting of divinyl sulfone (DVS), polyethylene glycon divinyl sulfone (VS-PEG-VS), hydroxyethyl methacrylate divinyl sulfone (HEMA-DIS-HEMA), formaldehyde, glutaraldehyde, aldehydes, isocyanates, alkyl and aryl halides, imidoesters, N-substituted maleimides, acylating compounds, carbodiimide, hydroxychloride, N-hydroxysuccinimide, light, pH, temperature, and combinations thereof.

56. The method of claim 37, wherein the biocompatible scaffold comprises a bioabsorbable material.

57. The method of claim 37, wherein the biocompatible scaffold comprises a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, tyrosine-derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, polyurethanes, biosynthetic polymers and combinations thereof.

58. The method of claim 57, wherein the biocompatible scaffold comprises an aliphatic polyester selected from the group consisting of homopolymers or copolymers of lactides;

glycolides;

ε

-caprolactone;

hydroxybuterate;

hydroxyvalerate;

1,4-dioxepan-2-one;

1,5,8,12-tetraoxyacyclotetradecane-7,14-dione;

1,5-dioxepan-2-one;

6,6-dimethyl-1,4-dioxan-2-one;

2,5-diketomorpholine;

p-dioxanone (1,4-dioxan-2-one);

trimethylene carbonate (1,3-dioxan-2-one);

alkyl derivatives of trimethylene carbonate;

δ

-valerolactone;

β

-butyrolactone;

γ

-butyrolactone;

ε

-decalactone;

pivalolactone;

α

,α

-diethylpropiolactone;

ethylene carbonate;

ethylene oxalate;

3-methyl-1,4-dioxane-2,5-dione;

3,3-diethyl-1,4-dioxan-2,5-dione;

6,8-dioxabicycloctane-7-one; and

combinations thereof.

59. The method of claim 37, wherein the biocompatible scaffold comprises a natural polymer selected from the group consisting of a fibrin-based material, a collagen-based material, a hyaluronic acid-based material, a cellulose-based material, silk and combinations thereof.

60. The method of claim 37, wherein the biocompatible scaffold comprises a ceramic selected from the group consisting of hydroxyapatite, α

-tricalcium phosphate, β

-tricalcium phosphate, calcium phosphate, calcium carbonate, calcium sulfate, bioglass, allogeneic bone graft material, xenogeneic bone graft material and combinations thereof.

61. The method of claim 36, wherein the biocompatible scaffold comprises a polymeric foam component having pores with an open cell pore structure.

62. The method of claim 61, wherein the biocompatible scaffold further comprises a reinforcing component formed of a biocompatible mesh-containing material.

63. The method of claim 62, wherein the foam component is integrated with the reinforcing component such that the pores of the foam component penetrate the mesh of the reinforcing component and interlock with the reinforcing component.

64. The method of claim 36, wherein the biocompatible scaffold further comprises at least one additional biological component applied thereto.

65. The method of claim 64, wherein the at least one additional biological component comprises growth factors, matrix proteins, enzymes, cytokines, viruses, nucleic acids, peptides, isolated cells, platelets or combinations thereof.

66. The method of claim 36, wherein the finely divided, minced tissue particles further comprise a plurality of cells, and at least a portion of the plurality of cells are transfected or transduced using a vector including at least one gene.

67. The method of claim 65, wherein the vector comprises a viral vector or a non-viral vector.

68. The method of claim 66, wherein the at least one gene encodes a gene product of interest.

69. The method of claim 68, wherein the gene product of interest comprises proteins, polypeptides, interference ribonucleic acid (iRNA) or combinations thereof.

70. The method of claim 36, wherein the method of treating tissue is a tissue treatment technique selected from the group consisting of tissue repair, tissue bulking, cosmetic treatment, therapeutic treatment, tissue augmentation, and tissue sealing.

71. A method of preparing a tissue implant, comprising:

providing a bioimplantable scaffold;

obtaining a sample of tissue;

processing the sample of tissue under aseptic conditions to form at least one tissue fragment and a physiological buffering solution; and

depositing the tissue fragment on the bioimplantable scaffold to yield a tissue implant.

72. The method of claim 71, wherein the bioimplantable scaffold comprises a synthetic polymer, a natural polymer, an injectable gel, a ceramic material, autogeneic tissue, allogeneic tissue, xenogeneic tissue, and combinations thereof.

73. The method of claim 71, wherein the method further comprises the step of incubating the tissue implant for a duration and under conditions effective to allow cells within the at least one tissue fragment to populate the scaffold.

74. The method of claim 71, wherein the tissue implant is incubated for a duration in the range of about 7 days to 6 weeks.

75. The method of claim 74, wherein the tissue implant is incubated at a temperature in the range of about 20 to 40°

C. and in an atmosphere having high humidity.

76. The method of claim 71, wherein the at least one tissue fragment comprises tissue selected from the group consisting of cartilage tissue, meniscal tissue, ligament tissue, tendon tissue, skin tissue, muscle tissue, periosteal tissue, pericardial tissue, synovial tissue, nerve tissue, kidney tissue, bone marrow, liver tissue, bladder tissue, pancreas tissue, spleen tissue, and combinations thereof.

77. The method of claim 76, wherein the at least one tissue fragment comprises autologous tissue.

78. The implant of claim 71, where in the at least one tissue fragment comprises a bone-free tissue type selected from the group consisting of cartilage, meniscus, tendon, ligament and combinations thereof.

79. The method of claim 71, wherein the at least one tissue fragment comprises an effective amount of viable cells that can migrate out of the tissue fragment.

80. The method of claim 79, wherein the effective amount of cells migrate out of the tissue fragment and populate an outer surface of the bioimplantable scaffold.

81. The method of claim 79, wherein the effective amount of cells migrate out of the tissue fragment and populate at least a portion of an interior region of the scaffold, such that the cells are embedded within the scaffold.

82. The method of claim 71, further comprising the additional step of providing at least one additional bioimplantable scaffold and placing the at least one additional bioimplantable scaffold over the deposited at least one tissue fragment, such that at least a portion of the at least one tissue fragment is disposed between at least two bioimplantable scaffolds.

83. The method of claim 71, wherein the bioimplantable scaffold further comprises an adhesion agent for anchoring the at least one minced tissue fragment to the bioimplantable scaffold.

84. The method of claim 83, wherein the adhesion agent comprises an anchoring agent selected from the group consisting of hyaluronic acid, fibrin glue, fibrin clot, collagen gel, alginate gel, gelatin-resorcin-formalin adhesive, mussel-based adhesive, dihydroxyphenylalanine (DOPA) based adhesive, chitosan, transglutaminase, poly(amino acid)-based adhesive, cellulose-based adhesive, synthetic acrylate-based adhesives, platelet rich plasma (PRP), Matrigel, Monostearoyl Glycerol co-Succinate (MGSA), Monostearoyl Glycerol co-Succinate/polyethylene glycol (MGSA/PEG) copolymers, laminin, elastin, proteoglycans and combinations thereof.

85. The method of claim 83, wherein the adhesion agent comprises a cross-linking agent selected from the group consisting of divinyl sulfone (DVS), polyethylene glycon divinyl sulfone (VS-PEG-VS), hydroxyethyl methacrylate divinyl sulfone (HEMA-DIS-HEMA), formaldehyde, glutaraldehyde, aldehydes, isocyanates, alkyl and aryl halides, imidoesters, N-substituted maleimides, acylating compounds, carbodiimide, hydroxychloride, N-hydroxysuccinimide, light, pH, temperature, and combinations thereof.

86. The method of claim 71, wherein the bioimplantable scaffold comprises a bioabsorbable material.

87. The method of claim 72, wherein the bioimplantable scaffold comprises a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), poly(propylene fumarate), copoly(ether-esters), polyalkylene oxalates, polyamides, tyrosine-derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, polyurethanes, biosynthetic polymers and combinations thereof.

88. The method of claim 87, wherein the biocompatible scaffold comprises an aliphatic polyester selected from the group consisting of homopolymers or copolymers of lactides;

glycolides;

ε

-caprolactone;

hydroxybuterate;

hydroxyvalerate;

1,4-dioxepan-2-one;

1,5,8,12-tetraoxyacyclotetradecane-7,14-dione;

1,5-dioxepan-2-one;

6,6-dimethyl-1,4-dioxan-2-one;

2,5-diketomorpholine;

p-dioxanone (1,4-dioxan-2-one);

trimethylene carbonate (1,3-dioxan-2-one);

alkyl derivatives of trimethylene carbonate;

δ

-valerolactone;

β

-butyrolactone;

γ

-butyrolactone;

ε

-decalactone;

pivalolactone;

α

,α

-diethylpropiolactone;

ethylene carbonate;

ethylene oxalate;

3-methyl-1,4-dioxane-2,5-dione;

3,3-diethyl-1,4-dioxan-2,5-dione;

6,8-dioxabicycloctane-7-one; and

combinations thereof.

89. The method of claim 72, wherein the bioimplantable scaffold comprises a natural polymer selected from the group consisting of a fibrin-based material, a collagen-based material, a hyaluronic acid-based material, a cellulose-based material, silk and combinations thereof.

90. The method of claim 72, wherein the bioimplantable scaffold comprises a ceramic selected from the group consisting of hydroxyapatite, α

-tricalcium phosphate, β

-tricalcium phosphate, bioglass, allogeneic bone graft material, xenogeneic bone graft material and combinations thereof.

91. The method of claim 71, wherein the bioimplantable scaffold comprises a polymeric foam component having pores with an open cell pore structure.

92. The method of claim 91, wherein the bioimplantable scaffold further comprises a reinforcing component formed of a biocompatible mesh-containing material.

93. The method of claim 92, wherein the foam component is integrated with the reinforcing component such that the pores of the foam component penetrate the mesh of the reinforcing component and interlock with the reinforcing component.

94. The method of claim 71, wherein the bioimplantable scaffold further comprises at least one additional biological component applied thereto.

95. The method of claim 94, wherein the at least one additional biological component comprises growth factors, matrix proteins, enzymes, cytokines, viruses, nucleic acids, peptides, isolated cells, platelets or combinations thereof.

96. A method for measuring the effect of a substance on living tissue, comprising the steps of:

(a) creating a tissue construct by providing a biocompatible scaffold, obtaining a sample of tissue, processing the sample of tissue to form at least one tissue fragment, depositing the at least one tissue fragment on the biocompatible scaffold such that the at least one tissue fragment is associated with the biocompatible scaffold, thereby forming a tissue construct, and incubating the tissue construct for a duration and under conditions that are effective to allow cells within the tissue fragment to populate the scaffold;

(b) contacting the tissue construct with a substance; and

(c) determining the effects of the substance on the tissue construct.

97. The method of claim 96, wherein the substance comprises a drug, a pharmaceutical composition, a chemical, a microbe, an element, a cytokine, a growth factor, a hormone, an antibody, a peptide, a ligand, an antagonist of membrane-bound receptors, or combinations thereof.