Self Assembling Elastin-Growth Factor Chimeric Nanoparticles for the Treatment of Chronic Wounds

Chronic wounds are associated with poor epidermal and dermal remodeling. Previous work has shown the efficacy of keratinocyte growth factor (KGF) in re-epithelialization and elastin in dermal wound healing. Here we demonstrate the fabrication of a fusion protein comprising of elastin like peptides (ELPs) and KGF. This fusion protein retains the biological activity of KGF and elastin as evidenced by its enhancement of keratinocyte and fibroblast proliferation. It also preserved the characteristic ELP inverse phase transitioning allowing the recombinant protein to be expressed in E-Coli and purified rapidly and easily using inverse temperature cycling (ITC). The fusion protein self-assembled into nanoparticles at physiological temperatures. When applied to full thickness wounds in diabetic mice these particles enhanced reepithelialization and granulation, by 2- and 3-fold respectively. The data strongly suggests the efficacy of these self-assembled nanoparticles in the treatment of chronic wounds resulting from diabetes or other underlying circulatory conditions.