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We found that (a) miR-146a levels inversely affect macrophage accumulation, foreign body giant cell (FBGC) formation, and fibrosis in a murine implant model; (b) macrophage-derived miR-146a is a crucial regulator of the FBR and FBGC formation, as confirmed by global and cell-specific knockout of miR-146a; (c) miR-146a modulates genes related to inflammation, fibrosis, and mechanosensing; (d) miR-146a modulates tissue stiffness near the implant during FBR; and (e) miR-146a is linked to F-actin production and cellular traction force induction, which are vital for FBGC formation. These novel findings suggest that targeting macrophage miR-146a could be a selective strategy to inhibit FBR, potentially improving the biocompatibility of biomaterials.<\/jats:p>","DOI":"10.1101\/2024.04.03.588018","type":"posted-content","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T19:10:21Z","timestamp":1712257821000},"source":"Crossref","is-referenced-by-count":0,"title":["Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial 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