The development of bone regenerative substitutes capable of orchestrating osteogenesis within inflammatory immune microenvironments remains a critical challenge. This study investigates the dual-functional immunomodulatory peptide DP7-C as a microRNA (miRNA) co-delivery system to regulate osteogenic differentiation and macrophage polarization synchronously. Through systematic screening of DP7-C/miRNA nanocomplexes (miR-21, -26a, -29a, -34a, -124, -125a) in bone marrow mesenchymal stem cells (BMSCs) and RAW264.7 macrophages, we identified DP7-C/miR-124 as the optimal nanocomplex, demonstrating synergistic osteoimmunomodulatory effects. Results demonstrated that the DP7-C/miR-124 combination raised the expression of anti-inflammatory factors in inflammatory macrophages and decreased the expression of pro-inflammatory factors. It also stimulated the production of osteogenesis-related proteins BMP2 and Runx2 to promote BMSC osteogenesis. Mechanistic studies revealed bidirectional cellular crosstalk, where DP7-C/miR-124 enhanced IL-10-mediated anti-inflammatory macrophage polarization while reciprocally promoting BMSC differentiation through paracrine modulation. These findings establish DP7-C/miRNA nanocomplexes as next-generation osteoimmunomodulatory biomaterials that concurrently resolve inflammation and amplify bone regeneration through epigenetic-immune circuit regulation, offering a promising strategy for functionalized bone defect repair in inflammatory microenvironments.
Fu et al. (Sun,) studied this question.
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