Engineering Efferocytosis for Bone Regeneration

Bone is an incredibly robust tissue thanks to its high blood supply, rapid cell turnover, and continuous remodeling. A significant body of research investigates strategies to improve osteogenesis, angiogenesis, and immunomodulation for bone regeneration, facilitated by numerous various therapeutic approaches (e.g. pharmacologics, biomaterials, stem cell therapy, and more). However, a critically understudied but recently emerging area of research lies in the inflammatory cascade and the cleanup of apoptotic cells during repair, aging, and disease. Termed "efferocytosis," this natural and efficient cleaning up of cells at the end of their lifespan is a crucial step in resolving injury, controlling disease, maintaining homeostasis, and tissue repair. Currently, the primary mechanism(s) driving efferocytosis in most tissue but especially bone, is unknown. Despite this knowledge gap, mounting evidence suggests that impaired efferocytosis plays a significant role in many chronic illnesses and impairs tissue regeneration. Biomaterials-based interventions are well-positioned to interrogate mechanisms of efferocytosis due to their ability to provide local support and guide cellular activity not only in combination with but also without additional pharmaceutical aid. This review will highlight the current understanding of efferocytosis in bone and discuss cutting-edge biomaterials-based strategies to engineer efferocytosis for improved outcomes in bone regeneration.