Ma Xianwen, Zhou Qi, Liu Zhaofeng, Wang Yibei, Hu Yong
Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China.
Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Heliyon. 2024 Sep 24;10(19):e38385. doi: 10.1016/j.heliyon.2024.e38385. eCollection 2024 Oct 15.
Bone fracture regeneration poses significant clinical challenges due to complications such as delayed healing, nonunion, and the limitations of current treatments.
This study introduces a novel therapeutic approach utilizing biomimetic nanogels to silence the Ccl4 gene, aiming to promote bone repair by regulating macrophage polarization.
The nanogels, composed of tannic acid (TA) and small interfering RNA (siRNA), were designed for targeted gene delivery.
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.
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.
由于延迟愈合、骨不连等并发症以及当前治疗方法的局限性，骨折再生带来了重大的临床挑战。
本研究引入一种利用仿生纳米凝胶沉默Ccl4基因的新型治疗方法，旨在通过调节巨噬细胞极化来促进骨修复。
由单宁酸（TA）和小干扰RNA（siRNA）组成的纳米凝胶被设计用于靶向基因递送。
体外研究结果表明，siRNA介导的Ccl4减少显著改善了M2巨噬细胞极化，进而促进了骨髓间充质干细胞的成骨分化。观察到成骨标志物表达增加和矿物质沉积增强。纳米凝胶表现出最佳的粒径、稳定性和细胞摄取，生物相容性测定证实了它们的无毒性。
本研究强调了靶向siRNA递送在调节免疫反应以增强骨再生方面的潜力，为复杂的骨愈合情况提供了有前景的治疗选择。
