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Material geometry is known to influence macrophage attachment and phenotype, providing opportunities for the rational design of \u201cimmune\u2010instructive\u201d topographies to modulate macrophage function. Here, we developed a biomaterial systems consisting of two different \u201cimmune\u2010instructives\u201d 3D geometries: sphere\u2010shaped microspheres (MSs) and rod\u2010shaped short microfibers (MFs) to modulate macrophage function for tissue regeneration. In the injectable biomaterials, we found that varying ratios of MSs to MFs in the composites significantly influence macrophage recruitment and M2 polarization, with high ratios of MFs potentially inducing scar formation. Through a systematic comparison of the\u00a0promotive effects on tissue regeneration between MSs and MFs, we discovered that MSs and MFs exhibited a spatiotemporal synergistic effect on immunomodulation for tissue regeneration. Specially, MS rapidly triggered the foreign body reaction after implantation and enhance macrophage infiltration. Subsequently, the recruited macrophages underwent morphological changes upon contact with MFs, activating autophagy and polarizing toward the M2 phenotype, thereby accelerating collagen deposition. The developed immunomodulatory composites provide a promising strategy for engineering injectable biomaterials with immunomodulatory function that demonstrates desirable stimulation for tissue regeneration.<\/jats:p>","DOI":"10.1002\/adhm.202505156","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T09:21:07Z","timestamp":1770369667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Spatiotemporal Synergistic Effects of Injectable Biomaterials With Two Typical 3D Geometries on Macrophage Modulation for Enhanced Tissue Regeneration"],"prefix":"10.1002","volume":"15","author":[{"given":"Liangwei","family":"Si","sequence":"first","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering Jiangsu Key Laboratory For Biomaterials and Devices School of Biological Science and Medical Engineering Southeast University  Nanjing 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