hypergranulation in excision wounds – differential roles for wound bed derived IL-1α and TNF-α

In this study it was determined i) whether an autologous skin substitute (SS) which heals chronic wounds could heal excision wounds, and ii) whether soluble proteins present in chronic and excision wound exudates might influence the potency of the SS and in turn the final outcome of wound healing. For clinical applications, SS were applied to tumor excision wounds. For mechanistic studies, SS culture medium was supplemented with exudates from excision or chronic wounds, with or without anti-IL-1α or anti-TNF-α. To determine SS potency, granulation-stimulation-mediators (CCL2/MCP-1, IL-6, CXCL1/Gro-α, CXCL8/IL-8) in culture supernatants were analysed by ELISA. The SS caused hypergranulation within 1 week after application to excision wounds resulting in delayed wound healing. Wound exudates isolated from chronic wounds or excision wounds resulted in a huge increase in secretion of granulation-stimulatory-mediators from SS. Antibodies against IL-1 α decreased this secretion in the case of chronic wound exudates whereas antibodies against TNF-α decreased this secretion in the case of excision wounds. In its current form the SS is not suitable for healing excision wounds. However, a potential combined therapy of anti-TNF-α and SS may provide a novel means to heal acute wounds since it might be expected to inhibit granulation tissue formation.