Bioactivity of the recombinant human antimicrobial peptide LL37: a key role in wound healing through vascularization

Antimicrobial peptides (AMPs) are usually defined as small, cationic,amphipathic peptides making part of the innate immune system.Human cathelicidin AMP LL37 is overexpressed in different cells, tis-sues and body fluids and, in addition to its antimicrobial activity,induces chemotaxis of immune system’ cells, arteriogenesis, angiogene-sis and promotes wound healing. Our group developed a new, low-costmethod for the expression and purification of LL37, by fusing it withthe Carbohydrate Binding Module from family 3 (CBM3) from CipAfrom Clostridium thermocellum. The CBM3-LL37 protein is overexpres-sed in E. coli and retained both the antibacterial and immunophysio-logic properties. Additionally, it induced proliferation, migration andformation of tubule-like structures by endothelial cells. Topical applica-tion of rLL37 also increased vascularization and re-epithelialization,thus accelerating the wound healing process, in wounds of dexametha-sone-treated mice. This indicates a key role for LL37 in wound regener-ation, mainly mediated by its proangiogenic activity, which is currentlybeing studied with further detail in diabetic mice, a chronic woundmodel. Moreover, we are working on the development of natural poly-mer-based delivery systems for the topical sustained release of LL37that can be applied to wound sites, thus promoting faster and moreefficient wound regeneration.