Biosynthetic materials for pro-regenerative immune modulation

Abstract

Monocyte and macrophage recruitment underlies the host response to myriad tissue injuries and thus represents a powerful therapeutic target to potentially augment healing in numerous clinical indications with unmet need. Our overarching objective is to effectively control the trafficking and function of non-classical monocytes to enhance tissue repair. To accomplish the objective, we develop and evaluate novel, implantable, biosynthetic materials. This research shows that (i) local manipulation of chemokines using biosynthetic materials enhances the recruitment of non-classical monocytes and stimulates angiogenesis and arteriogenesis, processes critical to regeneration of vascularized tissues; (ii) biosynthetic materials can harness functional synergy between chemokine and sphingolipid signals to enhance pro-regenerative monocyte and macrophage recruitment and arteriogenesis; and (iii) immune cell infiltration exerts anti-degenerative effects on rotator cuff muscle after severe rotator cuff injury. The work helps elucidate the role of specific molecular signals in immune cell recruitment and tissue vascularization, and presents biomaterial platforms that may aid tissue regeneration by harnessing these signals. By demonstrating the role of immune cell infiltration in rotator cuff muscle degeneration, the work may inform the design therapeutic interventions for rotator cuff injury.