Tissue-engineered skin is a novel therapeutic with which difficult-to-heal lower extremity wounds may be treated. Such skins are products of cutaneous tissue engineering that provide an alternative for autologous or allogeneic tissue transplantation, thereby avoiding problems associated with donor site availability, the risk of infection, and scarring. Recently developed tissue-engineered skin equivalents have shown tobe superior in certain ways to compression therapy for refractory venous ulcers and acute wounds. These biologic products behave similarly to autografts.
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References
1.
1. Carrel A, Burrows MT. Cultivation of adult tissues and organs outside the body. JAMA 1910;1379-1384.
2.
2. Hadda S. Die kultur lebender Zellen. Klin Wschr1912;49:11-19.
3.
3. Kreibich K. Kultur erwachsener Haut auf festem Nährboden. Arch Dermatol Syph1914;120:168-178.
4.
4. Andreassi L. History of keratinocyte cultivation. Burns1992;18:S2-S4.
5.
5. Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell1975;6:331-343.
6.
6. Barrandon Y, Li V, Green H. Newtechniques for the grafting of culturedhumanepidermal cells onto athymic animals. J Invest Dermatol1988;91:315-318.
7.
7. Barreca A, De Luca M, Del Monte P, et al. In vitro paracrine regulation of human keratinocyte growth by fibroblast-derived insulin-like growth factors. J Cell Physiol1992;151:262-268.
8.
8. Bettger WJ, Boyce ST, Walthall BJ, Ham RG. Rapid clonal growth and serial passage of human diploid fibroblasts in a lipid-enriched syntheticmediumsupplemented with epidermal growth factor, insulin, and dexamethasone. Proc Natl Acad Sci USA1981;78:5588-5592.
9.
9. Watt FM. Proliferation and terminal differentiation of human epidermal keratinocytes in culture. Biochem Soc Trans1988;16:666-668.
10.
10. Germain L, Rouabhia M, Guignard R, et al. Improvement of human keratinocyte isolation and culture using thermolysin. Burns1993;19:99-104.
11.
11. Hultman CS, Brinson GM, Siltharm S, et al. Allogeneic fibroblasts used to grow cultured epidermal autografts persist in vivo and sensitize the graft recipient for accelerated second-set rejection. J Trauma1996;41:51-60.
12.
12. Wu YJ, Parker LM, Binder NE, et al. The mesothelial keratins: a new family of cytoskeletal proteins identified in cultured mesothelial cells and nonkeratinizing epithelia. Cell1982;31:693-703.
13.
13. Green H. Cyclic AMP in relation to proliferation of the epidermal cell a new view. Cell1978;15:801-811.
14.
14. Rheinwald JG, Green H. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature1977;265:421-424.
15.
15. Leigh IM, Mc Kay I, Carver N, Navsaria H, Green C. Skin equivalents and cultured skin: from petri dish to the patient. Wounds1991;3:141-148.
16.
16. Boyce ST, Ham RG. Calcium-regulated differentiation of normal epidermal keratinocytes in chemically defined clonal and serum-free serial culture. J Invest Dermatol1983;81:33s-40s.
17.
17. Hennings H, Micheal D, Cheng C, et al. Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell1980;19:245-254.
18.
18. Green H, Kehinde O, Thomas J. Growth of cultured human epidermal cells into multiple epithelia suitable for grafting. Proc Natl Acad Sci U S A1979;76:5665-5668.
19.
19. O’Connor NE, Mulliken JB, Banks-Schlegel S, Kehinde O, Green H. Grafting of burns with cultured epithelium prepared from autologous epidermal cells. Lancet1981;i:75-78.
26. Gilchrest BA. In vitro assessment of keratinocyte aging. J Invest Dermatol1983;81:184s-189s.
27.
27. Munster AM, Weiner SH, Spence RJ. Cultured epidermis for the coverage of massive burn wounds. A single center experience. Ann Surg1990;211:679-680.
28.
28. Herzog SR, Meyer A, Woodley D, Peterson HD. Wound coverage with cultured autologous keratinocytes: use after burn wound excision, including biopsy follow-up. J Trauma1988;28:195-198.
29.
29. Rochat A, Kobayashi K, Barrandon Y. Location of stem cells of human hair follicles by clonal analysis. Cell1994;76:1063-1073.
30.
30. Gharzi A, Reynolds AJ, Jahoda CA. Plasticity of hair follicle dermal cells in wound healing and induction. Exp Dermatol2003;12:126-136.
31.
31. Limat A, French LE, Blal L, et al. Organotypic cultures of autologous hair follicle keratinocytes for the treatment of recurrent leg ulcers. J Am Acad Dermatol2003;48:207-214.
32.
32. Rennekampff HO, Kiessig V, Hansbrough JF. Current concepts in the development of cultured skin replacements. J Surg Res1996;62:288-295.
33.
33. Phillips TJ, Kehinde O, Green H, Gilchrest BA. Treatment of skin ulcers with cultured epidermal allografts. J Am Acad Dermatol1989;21:191-199.
34.
34. De Luca M, Albanese E, Cancedda R, et al. Treatment of leg ulcers with cryopreserved allogeneic cultured epithelium. A multicenter study. Arch Dermatol1992;128:633-638.
35.
35. Mol MAE, Nanninga PB, van Eendenburn JP, et al. Grafting of venous leg ulcers: an intraindividual comparison between cultured skin equivalents and full-thickness skin punch grafts. J Am Acad Dermatol1991;24:77-82.
36.
36. Teepe RGC, Koebrugge EJ, Ponec M, Vermeer BJ. Fresh versus cryopreserved cultured allografts for the treatment of chronic skin ulcers. Br J Dermatol1990;122:81-89.
37.
37. Teepe RGC, Roseeuw DI, Hermans J, et al. Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressing in healing chronic venous ulcers. J Am Acad Dermatol1993;29:982-988.
38.
38. Teepe RGC, Kreis RW, Koebrugge EJ, et al. The use of cultured autologous epidermis in the treatment of extensive burn wounds. J Trauma1990;30:269-275.
39.
39. Stark GB, Kaiser HW. Cologne Burn Centre experience with glycerol-preserved allogeneic skin: Part II: Combination with autologous cultured keratinocytes. Burns1994;20:s34-s38.
40.
40. Barlow Y, Burt A, Clarke JA, et al. The use of a polymeric film for the culture and transfer of subconfluent autologous keratinocytes to patients. J Tissue Viabil1992;2:33-36.
41.
41. Hunyadi J, Farkas B, Bertenyi C, Olah J, Dobozy A. Keratinocyte grafting: a new means of transplantation for full-thickness wounds. J Dermatol Surg Oncol1988;14:75-78.
42.
42. Hafemann B, Hettich R, Ensslen S, et al. Treatment of skin defects using suspensions of in vitro cultured keratinocytes. Burns1994;20:168-172.
43.
43. Horch RE, Bannasch H, Kopp J, Andree C, Stark GB. Single-cell suspensions of cultured human keratinocytes in fibrin-glue reconstitute the epidermis. Cell Transplant1998;7:309-317.
44.
44. Kaiser HW, Stark GB, Kopp J, et al. Cultured autologous keratinocytes in fibrin glue suspension, exclusively and combined with STS-allograft (preliminary clinical and histological report of a new technique). Burns1994;20:23-29.
45.
45. Currie LJ, Sharpe JR, Martin R. The use of fibrin glue in skin grafts and tissue-engineered skin replacements: a review. Plast Reconstr Surg2001;108:1713-1726.
46.
46. Donaldson DJ, Maham JT, Smith CN. Newt epidermal cell migration over collagen and fibronectin involves different mechanisms. J Cell Sci1988;90:325-333.
47.
47. Horch R, Stark GB, Kopp J, Spilker G. Cologne Burn Centre with glycerol-preserved allogeneic skin: Part I: Clinical experiences and histological findings (overgraft and sandwich technique). Burns1994;20:s23-s26.
48.
48. Rennekampff HO, Hansbrough JF. Current status of cultured epidermal skin substitutes. In Horch RE, Munster AM, Achauer BM, editors, with forewords from Vacanti CA, Yannas IV. Cultured human keratinocytes and tissue engineered skin substitutes. New York: Thieme; 2001. p. 139-146.
49.
49. Turley EA, Bowman P, Kytryik MA. Effects of hyaluronate and hyaluronate binding proteins on cell motile and contact behaviour. J Cell Sci1985;78:133-145.
50.
50. Palmieri B. Heterologous collagen in wound healing: a clinical study. Int J Tissue React1992;14(suppl):21-25.
51.
51. Mian E, Martini P, Beconcini D, Mian M. Healing of open skin with collagen foils. Int J Tissue React1992;14(suppl):27-34.
52.
52. Phillips TJ, Bhawan J, Leigh IM, Baum HJ, Gilchrest BA. Cultured epidermal autografts and allografts: a study of differentiation and allograft survival. J Am Acad Dermatol1990;23:189-198.
53.
53. Cuono CB, Langdon R, Birchall N, Barttelbort S, Mc Guire J. Composite autologous-allogeneic skin replacement: development and clinical application. Plast Reconstr Surg1987;80:626-637.
54.
54. Clark RAF. Cutaneous tissue repair: basic biological considerations I. J Am Acad Dermatol1985;13:701-725.
55.
55. Choucair MM, Phillips TJ. What is new in clinical research in wound healing. Dermatol Clin 1997;45-58.
56.
56. Woodley DT, Briggaman RA, Herzog SR, et al. Characterization of “neo-dermis” formation beneath cultured human epidermal autografts transplanted on muscle fascia. J Invest Dermatol1990;95:20-26.
57.
57. Prunieras M, Regnier M, Woodley D. Methods for cultivation of keratinocytes with an air-liquid interface. J Invest Dermatol1983;81:28s-33s.
58.
58. Prunieras M, Regnier M, Schlotter M. New procedure for culturing human epidermal cells on allogenic or xenogeneic skin: preparation of recombined grafts. Ann Chir Plast1979;24:357-362.
59.
59. Krejci NC, Cuono CB, Langdon RC, Mc Guire J. In vitro reconstitution of skin: fibroblasts facilitate keratinocyte growth and differentiation on acellular reticular dermis. J Invest Dermatol1991;97:843-848.
60.
60. Hansbrough JF, Boyce ST, Cooper ML, Foreman TJ. Burn wound closure with cultured autologous keratinocytes and fibroblasts attached to a collagen-glycosaminoglycan substrate. JAMA1989;262:2125-2130.
61.
61. Boyce ST, Glatter R, Kitzmiller WJ. Treatment of chronic wounds with cultured skin substitutes: a pilot study. Wounds1995;7:24-29.
62.
62. Echinard C, Damour O,David MF et al. In vitro and in vivo studies of a hybrid artificial skin. XXVI World Cong Int College Surgeons 1988;1480-1480.
63.
63. Shahabeddin L, Berthod F, Damour O, Collomel C. Characterization of skin reconstructed on a chitosan-cross-linked collagenglycosaminoglycan matrix. Skin Pharmacol1990;3:107-114.
64.
64. Braye FM, Stefani A, Venet E, et al. Grafting of large pieces of human reconstructed skin in a porcine model. Br J Plast Surg2001;54:523-538.
65.
65. Ferretti A, Boschi E, Stefani A, et al. Angiogenesis and nerve regeneration in a model of human skin equivalent transplant. Life Sci2003;73:1985-1994.
66.
66. Cooper ML, Hansbrough JF, Spielvogel RL, et al. In vivo optimization of a living dermal substitute employing cultured human fibroblasts on a biodegradable polyglycolic acid or polyglactin mesh. Biomaterials1991;12:243-248.
67.
67. Fleischmajer R, Mac Donald ED, Contard P, Perlish JS. Immunochemistry of a keratinocyte-fibroblast co-culture model for reconstruction of human skin. J Histochem Cytochem1993;41:1359-1366.
68.
68. Hansbrough JF, Morgan JL, Greenleaf GE, Bartel R. Composite grafts of human keratinocytes grown on a polyglactin mesh-cultured fibroblast dermal substitute function as a bilayer skin replacement in full-thickness wounds on athymic mice. J Burn Care Rehabil1993; 14:485-494.
