Affiliation:
1. Department of Stomatology, Sichuan Provincial People's Hospital University of Electronic Science and Technology of China Chengdu China
2. General Dentistry Chongqing University Three Gorges Hospital Chongqing China
3. State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital Sichuan University Chengdu China
Abstract
AbstractObjectiveThis study investigates the DP7‐C/miR‐26a complex as a stable entity resulting from the combination of miR‐26a with the immunomodulatory peptide DP7‐C. Our focus is on utilizing DP7‐C loaded with miR‐26a to modulate the immune microenvironment in bone and facilitate osteogenesis.MethodsThe DP7‐C/miR‐26a complex was characterized through transmission electron microscopy, agarose electrophoresis, and nanoparticle size potentiometer analysis. Transfection efficiency and cytotoxicity of DP7‐C were assessed using flow cytometry and the CCK‐8 assay. We validated the effects of DP7‐C/miR‐26a on bone marrow mesenchymal stem cells (BMSCs) and macrophages RAW 264.7 through gene expression and protein synthesis assays. A comprehensive evaluation of appositional bone formation involved micro‐CT imaging, histologic analysis, and immunohistochemical staining.ResultsDP7‐C/miR‐26a, a nanoscale, and low‐toxic cationic complex, demonstrated the ability to enter BMSCs and RAW 264.7 via distinct pathways. The treatment with DP7‐C/miR‐26a significantly increased the synthesis of multiple osteogenesis‐related factors in BMSCs, facilitating calcium nodule formation in vitro. Furthermore, DP7‐C/miR‐26a promoted M1 macrophage polarization toward M2 while suppressing the release of inflammatory factors. Coculture studies corroborated these findings, indicating significant repair of rat skull defects following treatment with DP7‐C/miR‐26a.ConclusionThe DP7‐C/miR‐26a system offers a safer, more efficient, and feasible technical means for treating bone defects.
Funder
National Natural Science Foundation of China