Tissue Engineering of Cultured Skin Substitutes
During the last two centuries, replacement of lost skin by means of skin grafting has evolved into an essential component of reconstructive surgery. Grafting may be used to accelerate healing and reduce insensible fluid loss from burns and other wounds, r
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25
R. E. Horch
Contents 25.1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . 329
25.2
Currently Available Skin Substitutes According to Their Fundamental Features
25.3
Problems of Skin Substitution in Major Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330
25.4
Cultured Skin Developments . . . . . . . . . . . 332
25.5
Cultured “Sheet Grafts” (Cultured Epithelial Autografts) . . . . . . . . . . . . . . . . . . . . . . . . . 333
25.6
Cultured Human Cell Suspension Grafting 334
330
25.6.1 Membrane Cell Delivery Systems . . . . . . . 335 25.6.2 Alloplastic or Mixed Synthetic-Biological Cell Carriers . . . . . . . . . . . . . . . . . . . . . . . . 335 25.6.3 Cultured Cells and Biological Carriers . . . 336 25.7
Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 References . . . . . . . . . . . . . . . . . . . . . . . . . 338
25.1
Introduction
Wound closure and repair of skin defects belong to the elementary processes maintaining structural integrity of the human body, which relies on an intact skin barrier to protect against environmental influences. Skin, also known as the integument, not only is the body’s largest laminar organ, but also fulfils many complex duties, such as being part of the immune response. Within this process, the primary aim
of restitution is immediate re-epithelialization of any wounded surface [152]. Following Barronio’s sheep-skin transplant experiments (1804), it was the ground-breaking report of human skin grafting by Reverdin in 1871 that ever since has set the gold standard for skin replacement by means of transplantation of the patient’s own skin. Inspired by Theodor Billroth’s observation that small islands of epithelium sometimes appeared in the granulation tissue in cases of severe burns, then extended rapidly, thus contributing to the epithelialization of a wound, Reverdin investigated what would happen if small pieces of skin were placed directly on the granulating tissue. His successful experiments in a 53-year-old patient convinced the surgeons of his time and set the pace for further developments. This procedure may be performed either as a fullthickness or as any form of split-thickness skin grafting. Hence, any tissue-engineered skin substitute will have to compare to the performance of standard autologous skin grafts over time. Cultured human skin substitutes and living skin equivalents were initially developed to overcome the shortage of skin donor sites in those with extensive skin wounds, such as major burns. The intention was to prevent infection and desiccation and deliver cell guidance by dermal elements [82]. With such extensive burns, the wounded surfaces and loss of skin demanded the invention of various temporary or permanent skin substitutes. One simple reason is that there are too few skin resources on the patient’s own body that would allow for recovery. However, to achieve a long-term recovery, properties of both the dermal and the epidermal layers of
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