Design of a novel cell-permeable chimeric peptide to promote wound healing

Biological membranes are impermeable to almost all compounds having a molecular weight greater than 500 Da. Recently, cell penetrating peptides (CPPs) as delivery vehicles have attracted great interest in the medical sector for the development of novel therapeutic agents or cosmetic products. Herein, a wound healing promoting sequence, namely Tylotoin, was covalently coupled with a cell penetrating peptide to improve the delivery of Tylotoin across cellular membranes. Indeed, internalization studies indicated that the cellular uptake of these novel peptide conjugates into keratinocytes was significantly improved accompanied by good tolerability. In a scratch wound closure assay used to investigate the wound healing capability, the most promising novel peptide chimera (Tylotoin-sC18*) was found to promote the migration of keratinocytes indicating that the fusion to Tylotoin did not cause any loss in its activity. Even more, proliferative effects on keratinocytes were observed, an important step during the wound healing process. Still more encouraging is the capability of Tylotoin-sC18* to exhibit strong antimicrobial activities since the process of wound healing is often affected by bacterial infections. Owing to their multiple functions, the novel peptide chimera may have potential as future agents for the treatment of infected wounds.