Targeting delayed healing tissues: immune reprogramming of adaptive immune cells by biomaterials

The adaptive immune system plays a pivotal role in coordinating tissue regeneration. Effective tissue repair and functional recovery depend on precisely regulating adaptive immune cells, especially T and B lymphocytes, and their dynamic crosstalk with innate immune cells. The immunomodulatory effects of biomaterials on adaptive cells could be realized through their influence on innate immune cells. This presents a promising therapeutic strategy, in which biomaterials can be designed to modulate immune activity toward pro-regenerative pathways and enhance healing. This review summarizes current knowledge on the molecular mechanisms that distinguish efficient acute healing from pathological chronic or delayed repair processes. Special attention is given to how key physicochemical properties of biomaterials influence the behavior of immune cells, with a specific emphasis on modulating adaptive immune responses. Understanding these biomaterial-immune cell interactions would advance the fundamental understanding of immunomodulatory biomaterials and provide a rational framework for designing next-generation biomaterials with optimized properties. This approach would help harness the body's intrinsic immune mechanisms to improve the outcomes of tissue regeneration. Future studies will refine these design principles to accelerate clinical translation.