ObjectiveTo review the research progress regarding the effects of the local microenvironment after meniscal injury and immunomodulatory strategies for meniscal regeneration. MethodsRelevant literature on meniscal regeneration, macrophage polarization, and tissue engineering was retrieved. The mechanisms underlying immune microenvironment imbalance after injury were summarized, and immunomodulatory interventions were analyzed from four perspectives: drugs and bioactive molecules, stem cells and exosomes, biomaterials, and external physical stimuli. ResultsThe highly inflammatory microenvironment dominated by M1 macrophages after injury significantly hinders tissue repair. Current studies mainly promote functional meniscal regeneration through immunomodulatory interventions in four aspects: drugs and bioactive molecules inhibit inflammatory cascades by blocking inflammatory receptors and related signaling pathways; stem cells and exosomes modulate the local immune microenvironment through paracrine effects and enhance the functions of repair-related cells; functionalized biomaterials achieve synergy between immunomodulation and mechanical support through active component delivery, physicochemical property regulation, and structural design; and external physical stimuli, such as acoustic, electrical, and magnetic stimulation, serve as non-invasive auxiliary approaches for inflammation regulation and tissue repair. ConclusionRemodeling the immune microenvironment is critical for functional meniscal regeneration. Smart scaffolds with both mechanical support and immunomodulatory functions should be further developed.
