3D‐Printed StrontiumSilicate Hydrogel Scaffold Promotes Sensory Innervation and Tissue Regeneration Through Modulating Macrophage Senescence

ABSTRACT The development of effective therapies for tissue regeneration remains challenging due to the persistence of senescent cells and chronic inflammation within damaged tissues. Here, we present a 3D‐printed strontium silicate–based hydrogel scaffold (GG‐5SS) that enables sustained Sr 2 + release to reprogram the local regenerative microenvironment. GG‐5SS effectively alleviates macrophage senescence and remodels the senescence‐associated secretory phenotype (SASP) toward a pro‐regenerative state. Mechanistically, GG‐5SS suppresses the senescence‐derived axon repelling factor SEMA3A, thereby restoring the phosphorylation of LKB1 and GSK‐3β and facilitating sensory innervation, which is essential for tissue repair. The regenerative effect of GG‐5SS was abolished following sensory nerve depletion, confirming that neuro‐immune crosstalk is indispensable for Sr ions‐mediated regeneration. In both murine and rhesus macaque models, GG‐5SS markedly promoted granulation tissue innervation, collagen deposition, and accelerated wound closure. Collectively, this work highlights GG‐5SS as a bioengineered platform that integrates senescence modulation and neural regulation, offering a promising and translational strategy for advanced wound management.