Aspects of bio-engineering of human skin : towards clinical application

Abstract

Skin is the largest organ of the human body and protects it from detrimental effects of the surrounding environment. As skin is directly exposed to the outer environment, it frequently occurs that it is destroyed by accidents. Large full- thickness skin defects may result from burns but also from the surgical excision of congenital giant nevi or scar tissue. The treatment of large (> 40% total body surface area) full-thickness wounds represents a major challenge, as donor sites for autologous skin transplantation often are very limited, and transplantation of autologous split-thickness skin (the present gold standard of treatment) can lead to severe scarring, especially in children. These problems could be significantly reduced applying a bio-engineered autologous dermo-epidermal skin substitute. The Tissue Biology Research Unit (TBRU) has shown that collagen type I hydrogels are a promising scaffold for skin tissue engineering in pre-clinical models. As collagen hydrogels show weak mechanical properties, the first part of my work aimed on engineering human dermo-epidermal skin substitutes based on collagen type I hydrogels which were stabilised by both, plastic compression (established by a postdoctoral fellow in our team) and incorporated biodegradable meshes (established by me). I applied two different meshes of synthetic polymers to mechanically stabilise the collagen hydrogel. I was able to generate skin substitutes which developed into a near normal skin with a dermal compartment and a stratified epidermis in vitro and in vivo using a rat mod. Another aspect of skin tissue engineering and the second part of my work concerns the youngest patients possible, the unborn human fetus. Fetal surgery to treat spina bifida has been convincingly demonstrated to markedly improve the perspectives of the patients. However, closure of skin defects of a fetus is a challenge, and in such cases engineered autologous fetal skin might help. In a first step towards engineering fetal skin, I could successfully apply human amniotic fluid derived cells in the dermal compartment of dermo-epidermal skin analogues, instead of the usually used human dermal fibroblasts, and succeeded in obtaining a well stratified, near normal epidermis. Bio-engineered dermo-epidermal skin substitutes could serve, additionally to their clinical application, for pre-clinical testing of newly designed medicinal products.