Following skin injury, damaged tissue undergoes highly coordinated biological events to restore barrier function involving cross-talk between dermal fibroblasts and epidermal keratinocytes as well as their interaction with the extracellular matrix. A full-thickness in vitro human skin model (EpiDerm-FTTM) was used to evaluate the role of serum growth factors in cutaneous wound healing. This model is constructed from primary keratinocytes and fibroblasts and contains a functional barrier and fully developed basement membrane. Small epidermal-only wounds (3mm biopsy punch) or full-thickness wounds (cauterizer burns) were induced in the tissue model and monitored histologically from day 0 to day 6. Addition of 2% human serum demonstrated an increased rate of epithelial healing and fibroblast accumulation which could be abrogated in the presence of an EGFR tyrosine kinase inhibitor or a TGF-alpha neutralizing antibody. Gene expression analysis of the wounded area showed temporally regulated changes in mRNA expression of basement membrane components, collagens and genes involved in extracellular matrix remodeling on days 2, 4 and 6 post wounding. These results demonstrate that EpiDerm-FTTM is a useful in vitro skin model for investigating dermal-epidermal interactions during wound healing as well as for the evaluation of new therapeutics in the dermal wound healing process.
Puskar M.1, Armento A.2, Stolper G.2, Klausner M.2, Letasiova S.1, Hayden P.J.2
1MatTek IVLSL, Bratislava, Slovakia, 2MatTek Corporation, Ashland, MA, USA;