ArticleiScience2026
IL-4 and arginine synergy accelerates early bone regeneration via enhanced efferocytosis and ameliorated microenvironment.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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10 authors.
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Abstract
Host bone microenvironment is a critical factor for successful bone regeneration during implantation. In this work, we identified a spatiotemporal mismatch at drilling-induced injury sites where initial apoptosis outpaces macrophage recruitment, leading to apoptotic cell accumulation and oxidative stress that impairs osteogenic differentiation. To mitigate this phenomenon, we developed a synergistic strategy co-delivering interleukin 4 (IL-4) and arginine (Arg) to reprogram the microenvironment. Mechanistically, IL-4 recruits and polarizes macrophages toward a pro-reparative M2 phenotype, while Arg fuels the arginase-1 metabolic pathway to sustain continual efferocytosis and secretion of pro-regenerative cytokines. In a mouse bone injury model, transcriptomic and histological analyses confirmed that this strategy accelerates apoptotic clearance and establishes an M2-dominant environment, significantly enhancing early bone regeneration. Altogether, this work proposes a novel therapeutic paradigm targeting macrophage efferocytosis to resolve early microenvironmental imbalances, providing a promising therapeutic approach to promote bone defect healing and offering novel insights into optimizing host microenvironments for osseointegration following implantation.
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