Encapsulation of cell‐adhesive RGD peptides into a polymeric physical hydrogel to prevent postoperative tissue adhesion

Abstract

Peptides containing the sequence of arginine-glycine-aspartate (RGD), a famous adhesion moiety, can specifically conjugate integrins in cell membranes, and are usually applied to enhance cell adhesion after linking to solid substrates in tissue engineering or to nanoparticles in targeting delivery. This paper reveals, however, that free RGD peptides can assist in preventing tissue adhesion by blocking focal adhesion between cells and surfaces of barrier devices. In order to avoid a rapid peptide loss after straightforward injection of a peptide solution, we employed a thermosensitive injectable hydrogel composed of a biodegradable block copolymer poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) to encapsulate peptides cyclo(-RGDfK-). A sustainable release for one week was achieved in vitro. The rabbit model of sidewall defect and bowel abrasion was selected to examine the in vivo anti-adhesion efficacy. It reveals a significant reduction of postoperative peritoneal adhesion in the group of RGD-loaded PCLA-PEG-PCLA hydrogels. We interpret this excellent efficacy by the combination of two effects: first, our hydrogel affords a physical barrier to prevent adhesion between injured abdominal wall and cecum; second, the RGD molecules as integrin blockers released from the hydrogel assist the anti-adhesion.