The roles of FIAF during skin homeostasis and wound repair in normal and diabetic conditions.
Tan, Nguan Soon.
Date of Issue2007
School of Biological Sciences
Biomedical science has made major advances in understanding how cells grow Into functioning tissue. The signalling mechanism used to achieve this are slowly being dissected. Tissue engineering is the application of that knowledge to the building or repairing or organs, Including skin. the largest organ in the body. It is remarkable that an organ with a surface area of -2m2, which performs a multitude of essential functions for everyday Survival, requires so little medical maintenance for it to last a lifetime. The human skin protects the body from environmental insults as such as chemicals and microorganisms. It Is also critical for preventing the transepidermal water loss from our bodies. However, when skin does fall, for example with third·degree bums or chronic ulcers, the result are far from ideal with slow wound healing and Increased risk of hypertrophic scarring. Furthermore, defects in skin barrier function have detrimental effects leading to entry of poisonous SUbstances, Infection and severe water loss. There is a SUbstantial marker for products for burn therapy and tor repair of appropriate wound and other skin closure uses. Within the bum-treatment community, there Is a much Interest in 'skin replacements· to cover, especially large wounds. Because of improvements in resuscitation, Infection contrOl, nutritional support, and surgical aspects of wound management, even 95% burns of the body surface area are now survivable by children 50% of the time. Many efforts had been made to produce artificial skin for wound coverage. These include human cadaver allograft and xenografts. keratinocyte cultures (also known as CEA, cultured epithelial aut09rafts). cultured fibroblast cultures (also known as dermal substitutes) and various acellular substitutes. However, it Is Obvious that replacement of both epidermal and dermal layers Is Important for achieving optimal take of the cultured grafts and for optimizing the quality of wound healing. Development of complete epidermal-dermal skin replacement (organotyplc skin culture, OTC) will undOUbtedly greatly simplify burn management. Clinical application of this modality has already been tested. OTCs have been used to cover successfully clean elective wounds and to correct childhood hand syndactyly and flexion contractures characteristics of dystrophic epidermolysis bullosa. OTCs generate human skin grafts that shortly after grafting normalize their tissue architecture. basement membrane structure and barrier functions. Other benefits of skin graft Include rapid heeling with cosmetically satisfactory results (i.e. lacking of scarring). Although all these skin replacements are useful, the culture media used often contain serum or tissue extracts (e.g. bovine pituitary extract), both complex and undefined mixtures of compounds from animal origins (see Annex 1). They risk contamination from prions and animal-derived pathogens/vlrus. In fact. such shortcomings in tissue-engineered skins were recently highlighted(MacNeil. 2007). Another important role of the human skin is to reduce transepidermal water loss, i,e, barrier function. Barrier function is localized in the outermost layer of the skin - stratum corneum of the epidermis. The stratum corneum has been described as an arrayof impermeable keratin-filled cells embedded in a matrix of lipids. All dermal and acellular substitutes do not possess a stratum comeum and thus no barrier functions. Monolayer keratinocyte culture models failed to faithfully reproduce epithelial architecture. Again, of considerable advantages are the OTCs which reproduce the normal keratinocytes physiology in vitro. However, a key difference between cultured skin substitutes and intact skin is the profile of extracellular lipids that are found in the stratum corneum, which are crucial for barrier functions. Human skin contains seven forms of ceramides but the culture produced primilarily ceramides 1-3 and very lillle ceramides 6 and 7. The lipid profile of the commercially available skin equivalent cultures, like Epiderm®, were all defiCient in ceramides 5, 6 and 7. The potential transdermal therapeutics has led to many studies to improve permeability properties of In vitro skin equivalent cultures, Sometime it is desirable to improve the berrier function of the skin for medical, infant care or cosmetic reasons, while at other times it would be advantageous to lower the permeability barrier, to adminster drugs transdermally, for example. Pharmaceutical and cosmetic companies all have product that may come in contact with the skin and thus there is a need for validated assays that would enable them with early stage compounds to test for barrier functions without resorting to expensive animal testing.
DRNTU::Science::Biological sciences::Human anatomy and physiology