Parsing Inflammatory Cues in Angiogenesis using Bioactive Hydrogels

Abstract

Both angiogenesis and inflammation are inescapable in vivo responses to any type of biomaterials implanted for regeneration. Continuous progress has been made in biomaterial design to facilitate tissue interactions with an implant by reducing inflammation and/or by inducing angiogenesis. However, it becomes increasingly clear that the physiological processes of angiogenesis and inflammation are interconnected through various molecular mechanisms. The role of implant-induced inflammation in the formation of new blood vessels into tissue surrounding the implant remains unclear. Therefore, we used a polyethylene glycol (PEG) cross-linked tyrosine derived polycarbonate hydrogel system as a model of implantable biomaterials. As opposed to the degradation rate, modulus and protein adsorption decreased as the cross-linking degree increased, due to hydrophilic repellent properties of PEG, indicating the unique and tunable hydrogel properties. The hydrogels were hybridized with pro- or anti-angiogenic (or inflammatory) peptides using collagen or fibrin gel and used for in vitro and in vivo biological studies. The results show a clear interconnectivity between angiogenic and inflammatory activities, indicating an inflammatory mechanism regulating follow-up angiogenic processes in hydrogels. This study suggests a new concept of biomaterial design that utilizes flexible inflammatory parameters to control angiogenesis for the eventual success of biomaterial implants.