AbstractThe immune system plays a crucial role during tissue repair and wound healing processes. Biomaterials have been leveraged to assist in this in situ tissue regeneration process to dampen the foreign body response by evading or suppressing the immune system. An emerging paradigm within regenerative medicine is to use biomaterials to influence the immune system and create a pro-reparative microenvironment to instigate endogenously driven tissue repair. In this review, we discuss recent studies that focus on immunomodulation of innate and adaptive immune cells for tissue engineering applications through four biomaterial-based mechanisms of action: biophysical cues, chemical modifications, drug delivery, and sequestration. These materials enable augmented regeneration in various contexts, including vascularization, bone repair, wound healing, and autoimmune regulation. While further understanding of immune-material interactions is needed to design the next generation of immunomodulatory biomaterials, these materials have already demonstrated great promise for regenerative medicine.Lay SummaryThe immune system plays an important role in tissue repair. Many biomaterial strategies have been used to promote tissue repair, and recent work in this area has looked into the possibility of doing repair by tuning. Thus, we examined the literature for recent works showcasing the efficacy of these approaches in animal models of injuries. In these studies, we found that biomaterials successfully tuned the immune response and improved the repair of various tissues. This highlights the promise of immune-modulating material strategies to improve tissue repair.