Recent advances in immunoregulatory biomaterials for tendon healing: From immune remodeling to functional...

Tendon injury is a prevalent musculoskeletal disorder characterized by delayed healing, functional impairment, and diminished quality of life. Tendon repair is a dynamic process driven by immune regulation of tissue remodeling.This review summarizes the immunological mechanisms underlying tendon healing. In the early inflammatory phase, neutrophils and M1 macrophages trigger tissue degradation through TNF-α and IL-1β mediated NF-κB and MAPK pathways.As healing progresses, M2 macrophages and regulatory T cells promote inflammation resolution and extracellular matrix reconstruction via IL-10 and TGF-β signaling, thereby driving the transition from inflammation to regeneration. Moreover, this review highlights biomaterial-based immunomodulatory strategies for tendon repair, focusing on how material composition, surface topography, and physical cues regulate immune responses, and how bioactive molecules modulate macrophage polarization and T-cell homeostasis to promote inflammation resolution and regeneration. Furthermore, emerging strategies including chemical modification, physical stimulation (electrical, mechanical, magnetic), and intelligent responsive systems (pH, ROS, inflammatory cues) highlight the potential of integrating multiple immunomodulatory mechanisms into biomaterial design to synergistically regulate inflammation resolution, matrix remodeling, and collagen organization for functional tendon regeneration.