Approximately 1–2% of people in developed countries—particularly the elderly and sufferers of diabetes or obesity—will experience in their lifetime a chronic skin wound characterised by tissue loss without spontaneous healing. This represents a major public health concern and a burden of several billions of dollars to not only the European, but also the global economy. Unfortunately, this burden is likely to grow as the world’s population ages and as diabetes and obesity become increasingly prevalent. Considering the growing need for more effective wound treatment options, the objective of this MSCA Fellowship has been to develop a dynamic hydrogel system containing stimuli-degradable self-immolative polymers (SIPs) to act as ‘sense-and-deliver’ modules for releasing drugs into chronic wound environments. SIPs are ideally suited to this application because they undergo complete depolymerisation in response to biochemical cues, making them useful stimuli-responsive materials. This project has made significant progress toward a multi-responsive hydrogel for accelerating chronic wound healing. I have developed a modular platform for preparing synthetic block copolymers featuring self-immolative side-chains. In water, these polymers self-assemble into nanoparticles (‘SIPsomes’), which can be loaded with drugs for treating chronic skin wounds. Importantly, these SIPsomes can be degraded by biochemical signals present within the wound environment, thereby triggering the release of specific drugs at different stages of the wound healing process. As proof-of-concept, successful payload delivery in vitro from a peroxide-responsive SIPsome has been demonstrated. This SIPsome will be used to interrupt the chronic inflammatory cycle of chronic wounds by delivering an inhibitory drug in response to reactive oxygen species. Ongoing work seeks to expand the suite of SIPsomes to target other stages of wound healing (proliferation, remodelling) toward a multifunctional SIPsome hydrogel that dynamically addresses several wound healing stages.
This highly ambitious project involved collaborations between the Karolinska Institute and Imperial College London to synthesise and study this complex new biomaterial. The cross-disciplinary expertise from these collaborations, and my placement within the world-renowned Stevens Group, facilitated the promising outcomes of this project. Ongoing international collaborations established during this project will further develop this system for future clinical applications.
