The major applications of tissue-engineered
skin substitutes are in promoting the healing of acute and chronic
wounds. Several approaches have been taken by commercial companies to develop products to address these conditions.
Skin substitutes include both acellular and cellular devices. While acellular
skin substitutes act as a template for dermal formation, this discussion mainly covers cellular devices. In addressing therapeutic applications in tissue engineering generally, a valuable precursor is an understanding of the mechanism of the underlying pathology. While this is straightforward in many cases, it has not been available for wound healing. Investigation of the mode of action of the tissue-engineered
skin substitutes has led to considerable insight into the mechanism of formation, maintenance and treatment of chronic
wounds. Four aspects mediating healing are considered here for their mechanism of action: (i) colonization of the
wound bed by live fibroblasts in the implant, (ii) the secretion of
growth factors, (iii) provision of a suitable substrate for cell migration, particularly keratinocytes and immune cells, and (iv) modification of the immune system by secretion of neutrophil recruiting
chemokines. An early event in acute wound healing is an influx of neutrophils that destroy planktonic bacteria. However, if the bacteria are able to form biofilm, they become resistant to neutrophil action and prevent reepithelialization. In this situation the
wound becomes chronic. In chronic
wounds, fibroblasts show a senescence-like phenotype with decreased secretion of neutrophil
chemoattractants that make it more likely that biofilms become established. Treatment of the chronic
wounds involves
debridement to eliminate biofilm, and the use of antimicrobials. A role of
skin substitutes is to provide non-senescent fibroblasts that attract and activate neutrophils to prevent biofilm re-establishment. The emphasis of the conclusion is the importance of preventing contaminating bacteria becoming established and forming biofilms.