Biomimetic siRNA nanogels for regulating macrophage polarization and promoting osteogenesis.

BACKGROUND: Bone fracture regeneration poses significant clinical challenges due to complications such as delayed healing, nonunion, and the limitations of current treatments. OBJECTIVE: This study introduces a novel therapeutic approach utilizing biomimetic nanogels to silence the Ccl4 gene, aiming to promote bone repair by regulating macrophage polarization. METHODS: The nanogels, composed of tannic acid (TA) and small interfering RNA (siRNA), were designed for targeted gene delivery. RESULTS: In vitro findings indicate that siRNA-mediated Ccl4 reduction significantly improves M2 macrophage polarization, which, in turn, promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Increased expression of osteogenic markers and enhanced mineral deposition were observed. The nanogels demonstrated optimal particle size, stability, and cellular uptake, and biocompatibility assays confirmed their non-toxicity. CONCLUSION: This study underscores the potential of targeted siRNA delivery in modulating immune responses to enhance bone regeneration, offering promising treatment options for complex bone healing scenarios.