Dissecting Macrophage Mechanobiology to Engineer Immuno-Regenerative Biomaterials

There is an increasing clinical demand for sophisticated medical implants and the scientific field of implant technology is exponentially growing. The main challenge is to harness the immune response to such an implant. In this research we use the immune response to our advantage, by using bioresorbable synthetic biomaterials that are gradually replaced by living tissue inside the body. One of the key immune cells are macrophages, which are the gatekeepers for successful implant integration. Strategies to harness the macrophage response focus on isolated biomaterial design features, such as biochemical or microstructural modifications. One major neglected factor is how macrophages sense and respond to mechanical loads, such as cyclic stretch, or ‘macrophage mechanobiology’. Without an in-depth understanding of macrophage mechanobiology, rational engineering of biomaterials is not possible, leading to unpredictable outcomes and ineffective trial-and-error work. With MACxercise, I will leverage my unique multi-disciplinary expertise in bioengineering, biomaterial science and macrophage biology to address these scientific challenges from a new angle in which macrophage mechanobiology is placed center stage. The Main Aim of the MACxercise program is to systematically dissect how macrophages respond to dynamic mechanical cues and to establish how this affects biomaterial-driven tissue regeneration. The transformative strength of MACxercise lies in the concerted spatial and temporal manipulation of the macrophage microenvironment, using sophisticated engineering tools to decouple the mechanical and physical cues to systematically pinpoint how synergistic or conflicting cues dictate key macrophage functions in the biomaterial microenvironment. With MACxercise, my vision is to catalyze the establishment of an exciting new research field across the boundaries of biomaterial science, immunology, mechanobiology, and tissue engineering.