Synthetic Biodegradable Polymer Scaffolds

  • Gail K. Naughton
  • Ronnda Bartel
  • Jonathan Mansbridge
Chapter

Abstract

Over the last several decades, new technologies have enabled the in vitro cultivation of many different human cell types. At the same time, the art and science of medicine has been expanded to include new biopharmaceutical and recombinant genetic therapies. Organ transplantation has become commonplace, limited not by surgical technique but by donor availability. Tissue engineered organs can obviate the torturous waiting and the human tragedy caused by the scarcity of donor organs. Furthermore, tissue engineered organs can be used in testing procedures, reducing or eliminating the need for animal and human subject tests. The first tissue engineered organ, which has progressed from the lab bench to the first accepted patient care, has been skin, the body’s largest organ (Rheinwald, 1989). Tissue engineering offers many benefits to the patient and has the potential of redefining transplantation. Researchers can use standard, well-recognized cell-banking procedures to characterize the human cell source for these tissue products and to safety-test this source for possible contaminants (US FDA; 1993a). Normal human tissues may be more efficacious than animal or synthetic tissues because normal human tissues supply a balanced natural mixture of growth factors and both structural and interactive functional proteins. These tissues can communicate with the body’s own repair mechanisms to stimulate angiogenesis, remodeling, and other steps to restore complete function.

Keywords

Surfactant Migration Hepatitis Tyrosine Transportation 

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References

  1. Aaronson SA, Bottaro DP, Miki T, et al (1991): Keratinocyte growth factor. A fibroblast growth factor family member with unusual target cell specificity. Ann NY Acad Sci 638:62–77PubMedCrossRefGoogle Scholar
  2. Allen LA, Landeen LK, Pieters R, et al (1994): Development of a porcine full-thickness burn model for the evaluation of human cadaveric skin and Dermagraft Transitional Covering, a biosynthetic skin substrate. In: Proceedings of the 9th Congress of the International Society for Burns. Paris, FranceGoogle Scholar
  3. Bale JF, Kealey GP, Ebelhack CL, et al (1992): Cytomegalovirus infection in a cyclosporine-treated burn patient: A case report. J Trauma 32:263–267PubMedCrossRefGoogle Scholar
  4. Beck LS, Chen TL, Hirabayashi SE, et al (1989): Accelerated healing of ulcer wounds in the rabbit ear by recombinant human transforming growth factor-ßl. Growth Factors 2:273–282Google Scholar
  5. Bell E, Ivarsson B, Merril C (1979): Production of a tissue-like structure by construction of collagen lattices by human fibroblasts of different proliferative potential in vitro.Proc Natl Acad Sci USA 76:1274–1278PubMedCrossRefGoogle Scholar
  6. Bild DE, Selby JV, Sinnock P, et al (1989): Lower-extremity amputation in people with diabetes: Epidemiology and prevention.Diabetes Care 12:24PubMedCrossRefGoogle Scholar
  7. Black K, Gentzkow G, Purchio T, et al (1994): The future for temporary and permanent wound coverage. In: Proceedings of the 3rd International Congress on the Immune Consequences of Trauma, Shock and Sepsis. Munich, GermanyGoogle Scholar
  8. Blood S, Heck E, Baxter CR (1979): The importance of the bacterial flora in cadaver homograft burn donor skin. In: Proceedings of the 11th Meeting of the American Burn Association. New Orleans, LAGoogle Scholar
  9. Casterton PL, Potts LF, Klein BD (1994): Use of in vitro methods to rank surfactants for irritation potential in support of new product development. Toxicol In Vitro 8:835–836PubMedCrossRefGoogle Scholar
  10. Centers for Disease Control (1991): The Prevention and Treatment of Complications of Diabetes: A Guide for Primary Care Practitioners, NIH Publication No. 93–3464. Atlanta, GA: Centers for Disease ControlGoogle Scholar
  11. Committee for Proprietary Medicinal Products: Ad Hoc Working Party on Biotechnology/Pharmacy (1989): Notes to applicants for marketing authorizations on the production and quality control of monoclonal antibodies of murine origin intended for use in man. J Biol Stand 17:213CrossRefGoogle Scholar
  12. Contard P, Bartel RL, Jacobs L, et al (1993): Culturing keratinocytes and fibroblasts in a three-dimensional mesh results in epidermal differentiation and formation of a basal lamina-anchoring zone. J Invest Dermatol 100:35–39PubMedCrossRefGoogle Scholar
  13. Cuono C, Langdon R, McGuire J (1986): Use of cultured epidermal autografts and dermal allografts as skin replacement after burn injury. Lancet 1(8490):1123–1124PubMedCrossRefGoogle Scholar
  14. Cuono CB, Langdon R, Birchall N (1987): Composite autologous-allogenic skin replacement: Development and clinical application.Plast Reconstr Surg 80:626PubMedCrossRefGoogle Scholar
  15. Davis MM, Hansbrough JF, Mozingo DW, et al (1995): Conference Center, Harrogate Dermagraft-TC in the treatment of burns requiring temporary coverings. In: Proceedings of the Symposium on Advanced Wound Care and Medical Research Forum on Wound Repair. Google Scholar
  16. Demarchez M, Hartmann DJ, Regnier M, et al (1992): The role of fibroblasts in dermal vascularization and remodeling of reconstructed human skin after transplantation onto the nude mouse. Transplantation 54:317–356PubMedCrossRefGoogle Scholar
  17. DeWever B, Rheins LA (1994): Skin2™: An in vitro human skin analog. In: Alternative Methods in Toxicology, Vol. 10, Rougier A, Goldberg AM, Maibach HI, eds. New York: Mary Ann Leibert, IncGoogle Scholar
  18. Donnelly TA, Allen R, Edwards S, Rheins LA (1995): Dermal Matrix Deposition in an in vitro skin model following topical administration of alpha hydroxy acid (AHA) formulations.J Invest Derm 104:669Google Scholar
  19. Economou TP, Rosenquist MD, Lewis II RW, et al (1995): An experimental study to determine the effects of Dermagraft on skin graft viability in the presence of bacterial wound contamination. J Burn Care Rehab 16:27–30CrossRefGoogle Scholar
  20. Edwards SM, Donnelly TA, Sayre RM, et al (1994): Quantitative in vitro assessment of phototoxicity using a human skin model, Skin2™. Photodermatol Photoimmunol Photomed 10:111–117PubMedGoogle Scholar
  21. Falanga V, Grinnell F, Gilchrest B, et al (1994): Workshop on the pathogenesis of chronic wounds. J Invest Dermatol 102:125–27CrossRefGoogle Scholar
  22. Fleischmajer R, Contard P, Schwarz E, et al (1991): Elastin-associated microfibrils (10 nm) in a three-dimensional fibroblast culture. J Invest Dermatol 97:638–643PubMedCrossRefGoogle Scholar
  23. Fleischmajer R, MacDonald ED, Contard P, et al (1993): Immunochemistry of a keratinocyte-fibroblast co-culture model for reconstruction of human skin. J Histochem Cytochem 41:1359–1366PubMedCrossRefGoogle Scholar
  24. French CC, Van de Waters L, Dvorak H, et al (1989): Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat. J Cell Biol 109:903–914CrossRefGoogle Scholar
  25. Gentzkow G, Iwasaki S, Gupta S, et al (1994): Cultured Human Dermal Replacement Tissue for the Treatment of Diabetic Foot Ulcers Oxford, England: European Tissue Repair SocietyGoogle Scholar
  26. Hansbrough JF (1987): Biological dressings. In: The Art and Science of Burn Care, Boswick J, ed. Rockville, MD: Aspen PublishersGoogle Scholar
  27. Hansbrough JF (1990): Current status of skin replacements for coverage of extensive burn wounds. J Trauma 30:S155–162PubMedCrossRefGoogle Scholar
  28. Hansbrough JF (1995): Status of cultured skin replacements. Wounds 7:130–136Google Scholar
  29. Hansbrough JF, Cooper ML, Cohen R, et al (1992a): Evaluation of a biodegradable matrix containing cultured human fibroblasts as a dermal replacement beneath meshed skin grafts on athymic mice. Surgery 4:438–446Google Scholar
  30. Hansbrough JF, Dore C, Hansbrough WC (1992b): Clinical trials of a living dermal tissue replacement placed beneath meshed, split-thickness skin graft on excised burn wounds. J Burn Care Rehab 13:519–529CrossRefGoogle Scholar
  31. Hansbrough JF, Morgan J, Greenleaf G (1993): Advances in wound coverage using cultured cell technology. Wounds 5:174–194Google Scholar
  32. Hansbrough JF, Morgan J, Greenleaf B, et al (1994): Development of a temporary living skin replacement composed of human neonatal fibroblasts cultured in Bio- brane, a synthetic dressing material. Surgery 115:633–644PubMedGoogle Scholar
  33. Houck KA (1992): Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 267:26031–26037PubMedGoogle Scholar
  34. Ilten-Kirby B, Pinney E, Pavalec R, et al (1995): Human allograft vs. Dermagraft Transitional Covering, a tissue engineered skin substitute for use as a full-thickness burn covering. Proceedings of the 2nd Annual Conference on Cellular Engineering. San Diego, CA: International Federation for Medical and Biological EngineeringGoogle Scholar
  35. Jakoby WB, Pastan IB, eds. (1979): Cell Culture. In: Methods in Enzymology. 58 New York: Academic PressGoogle Scholar
  36. Kelly JL (1993): Accumulation of PDGF B and cell-binding forms of PDGF A in the extracellular matrix. J Cell Biol 121:1153–1163PubMedCrossRefGoogle Scholar
  37. Koschier FJ, Roth RN, Stephens TJ (1994): In vitro skin irritation testing of petroleum-based compounds in reconstituted human skin models. J Toxicol-Cut Ocular Toxicol 13:23–37CrossRefGoogle Scholar
  38. Kruse Jr PF, Patterson Jr MK, eds. (1973): Tissue Culture Methods and Applications. New York: Academic PressGoogle Scholar
  39. Landeen LK, Zeigler FC, Halberstadt C, et al (1992): Characterization of a human dermal replacement. Wounds 5:167–175Google Scholar
  40. Lane TF, Sage EH (1994): The biology of SPARC, a protein that modulates cell-matrix interactions. FASEB J 8:163–173PubMedGoogle Scholar
  41. Lane TF, Iruela-Arispe ML, Johnson RS, et al (1994): SPARC is a source of copper- binding peptides that stimulate angiogenesis. J Cell Biol 125:929–943PubMedCrossRefGoogle Scholar
  42. Langer R, Vacanti JP (1993): Tissue engineering. Science 260:920–926PubMedCrossRefGoogle Scholar
  43. Leary T, Jones PL, Appleby M, et al (1992): Epidermal keratinocyte self-renewal is dependent upon dermal integrity. J Invest Dermatol 99:422–430PubMedCrossRefGoogle Scholar
  44. Lucas-Clerc C, Massart C, Campion JP, et al (1993): Long-term culture of human pancreatic islets in an extracellular matrix: Morphological and metabolic effects. Mol Cell Endocrinol 94:9–20PubMedCrossRefGoogle Scholar
  45. Mansbridge M, Gould T, Pinney E, et al (1995): Control of growth and matrix deposition in three-dimensional culture of human fibroblasts. In: Proceedings of the 2nd Annual Conference on Cellular Engineering. San Diego, CA: International Federation for Medical and Biological EngineeringGoogle Scholar
  46. Masur SK, Idris A, Michelson K, et al (1995): Integrin-dependent tyrosine phosphorylation in corneal fibroblasts. Invest Ophthalmol Vis Sci 36:1837–1846PubMedGoogle Scholar
  47. Mayer FL, Whalen EA, Rheins LA (1994): A regulatory overview of alternatives to animal testing: United States, Europe, and Japan. J Toxicol-Cut Ocular Toxicol 13:3–22CrossRefGoogle Scholar
  48. Med PRO Monthly (1992): Wound healing: Focus on growth factors, skin substitutes. MedPRO Month 2:91Google Scholar
  49. Mulder GD, Patt LM, Sanders L, et al (1994): Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-L-histidyl-L-lysyl copper. Wound Rep Reg 2:259–269CrossRefGoogle Scholar
  50. Nunes I, Shapiro RL, Rifkin DB (1995): Characterization of latent TGF-beta activation by murine peritoneal macrophages. J Immunol 155:1450–1459PubMedGoogle Scholar
  51. Perkins MA, Osborne R (1993): Development of an in vitro method for skin corrosion testing. J Invest Dermatol 100:535Google Scholar
  52. Petricciani JC, Hennessen W, eds. (1987): Cells, products, safety: Background papers for the WHO study group on biologicals. In: Developments in Biological Standardization. 68 Karger S, ed. Basel SwitzerlandGoogle Scholar
  53. Petricciani JC, Hopps HE, Chappie PJ, eds. (1979): Cell Substrates. New York: PlenumGoogle Scholar
  54. Peus D, Jungtaubl H, Knaub S, et al (1995): Localization of platelet-derived growth factor receptor subunit expression in chronic venous leg ulcers. Wound Rep Reg 3:273–283CrossRefGoogle Scholar
  55. Pollock RA, Richardson WD (1992): The alternative-splice isoforms of the PDGF A-chain differ in their ability to associate with the extracellular matrix and to bind heparin in vitro. Growth Factors 7:267–277PubMedCrossRefGoogle Scholar
  56. Rheins LA, Edwards SM, Miao O, et al (1994): Skin2™: An in vitro model to assess cutaneous immunotoxicity. Toxicol In Vitro 8:1007–1014PubMedCrossRefGoogle Scholar
  57. Rheinwald JG (1989): Methods for clonal growth and serial cultivation of normal human epidermal keratinocytes and mesothelial cells. In: Cell Growth and Division: A Practical Approach, Baserga R, ed. New York: Oxford University PressGoogle Scholar
  58. Schwarzbauer JE (1991): Alternative splicing of fibronectin: Three variants, three functions. Bioessays 13:527–533PubMedCrossRefGoogle Scholar
  59. Slivka SR (1992): Testosterone metabolism in an in vitro skin model.Cell Biol Tox 8:267–277CrossRefGoogle Scholar
  60. Slivka SR, Landeen LK, Zeigler F, Zimher MP, Bartel RL (1992): Characterization, barrier function and drug metabolism of an in vitro skin model. J Invest Dermatol 93:40–46Google Scholar
  61. Takeda N, Abe S, Tsukiyama H, et al (1995): The Clinical Experience of Artificial Skin Contained Allogenic Fibroblasts. Nagoya, Japan: Japanese Society of Burn InjuryGoogle Scholar
  62. U.S. Food and Drug Administration (1993a): Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals. Bethesda, MD: U.S. Department of Health and Human ServicesGoogle Scholar
  63. U.S. Food and Drug Administration (1993b): Inspectional Guidance: Banked Human Tissue. Bethesda, MD: U.S. Department of Health and Human ServicesGoogle Scholar
  64. Werner S, Peters KG, Longaker MT, et al (1992): Large induction of keratinocyte growth factor in the dermis during wound healing. Proc Natl Acad Sci USA 89:6896–6900PubMedCrossRefGoogle Scholar
  65. White MJ, Whalen JD, Gould JA, et al (1991): Procurement and transplantation of colonized cadaver skin. Am Surg 57:402–407PubMedGoogle Scholar
  66. Wysocki AB, Staiano-Coico L, Grinnell F (1993): Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9.7 Invest Dermatol 101:64–68CrossRefGoogle Scholar
  67. Yamaguchi Y, Mann D, Ruoslahti E (1990): Negative regulation of transforming growth factor-p by the proteoglycan decorin.Nature 346:281–284PubMedCrossRefGoogle Scholar
  68. Yannas IV, Burke JF, Orgill DP, Skrabut EM (1982): Wound tissue can utilize a polymeric template to synthesize a functional extension of skin. Science 215:174–176PubMedCrossRefGoogle Scholar
  69. Zeigler FC, Landeen L, Naughton GK, et al (1993): Tissue-engineered, three-dimensional human dermis to study extracellular matrix formation in wound healing. J Toxicol-Cut Ocular Toxicol 12:303–312.CrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 1997

Authors and Affiliations

  • Gail K. Naughton
    • 1
  • Ronnda Bartel
    • 1
  • Jonathan Mansbridge
    • 1
  1. 1.Advanced Tissue Sciences Inc.La JollaUSA

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