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Experimental Reconstruction And Transplantation Of Endothelialized Living Dermal Substitute

Posted on:2003-04-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z G LiuFull Text:PDF
GTID:1104360092465027Subject:Surgery
Abstract/Summary:PDF Full Text Request
Experimental Reconstruction and Transplantation ofEndothelialized Living Dermal SubstituteBackround With the development of tissue engineering, it is possibie to replace the defect or injured organs with tissue-engineered organs. The clinical application of artificial skin, for instance, is a typically successful example, which is important to the treatment of patients with burn, traumatic injury, chronic skin ulcer or hyperthopic scar. The traditional approach is grafting autologous skin, which often results in heavy pigmentation and scarring in donor sites, and the amount of skin obtained by this method is limited for patients with large area skin injuries. The technique of skin tissue engineering has been a promising method to provide adequate skin grafts and improve wound healing quality. Various dermal analogs such as Integra, Alloderm, Dermagraft et al have been developed and used as dermal template to cover full-thickness wounds successfully. The dermal replacement grafted with thin autologous skin could shorten healing time of donor sites. The recipient sites have improved cosmesis and function with less pigmentation, wound contraction and better durability. However, these dermal substitutes derived from allogeneic skin have limited sources as well as slow vascularization or poor survival grafted simutaneously with autografts. The clinical application of these skin tissue-engineered productions usually needs two-step transplantation. The time between two operations depends on the time of dermis equivalents vascularization on the wound. Therefore, vascularization of dermal substitutes is one of the important aspects in skin tissue engineering study. Reconstruction of composite skin is the ultimate aim of skin tissue engineering. Artificial skin comprised complete cutaneous replacement-dermal and epidermal components. Even though it offers the ultimate possibility of a one-step burn wound closure, there seem to be a few drawbacks, such as the long culture time, lowantibacterial capacity and poor taking rate that restricts the use of skin equivalent. The prominent drawback is the poor survival and unpredictable viability after engraftment. Clinical use of composite skin in the extent of the burn wound, the take rete is only 50%. The proposed key reasons include poor diffusion of nutrients, lack of ready-formed capillary network and slow neovascularization. The datum have shown that the most likely mechanism for skin graft survival is diffusion of nutrients, followed by inosculation of the recipient bed capillaries to the severed ends of the graft vessels and neovascularization. It is difficult for the nutrients in plasma to pass through the Alloderm, an acellular allo-dermal matrix, because it is lack of effective microholes responsible for the diffusion of liquid. On the other hand, the composite skin does not contain capillaries. So epidermis could not take enough nutrition until the establishment of capillary vascular flow during weeks 1 to 2 postgraft, all these lead to the graft slough and dead. Therefore it is essential for the composite skin survival to nurture the keratinocytes seeded on the surface of dermal substitute. In recent years, the study on skin tissue engineering at home has been made and is still in progress. The acellular dermal matrix (ADM) has been prepared, but the same problem is low taking rate and poor vascularization. As for the living composite skin, it has a long way to be used in wound coverage although there were some successful reports. This demonstrates that the composite skin itself has some defects. Hence, living composite skin is not the simple reconstruction of scaffold and seed cells. There are many complicated problems to be solved in simulating the structure and function of human skin and making organ type skin substitute. The application of endothelial cells in tissue engineering is mainly in researching of endothelialized artificial vessels. There are a few reports of its application in skin tissue engineeing. The adhesive ability i...
Keywords/Search Tags:tissue engineering, dermal substitute, biomaterials, vascular endothelium, transplantation
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