Zhu Yan, Yu Xin, Hao Mingxuan, Wang Yushan, Fan Gentao, Qian Hongbo, Jiang Peng, Cai Zhengdong, He Zhiwei, Zhou Guangxin
Department of Orthopaedics, Jinling Hospital, Affiliated Hospital of Medical School, Southeast University, 210000 Nanjing, China.
Department of Orthopaedics, Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, China.
ACS Appl Bio Mater. 2025 Mar 17;8(3):2078-2089. doi: 10.1021/acsabm.4c01633. Epub 2025 Feb 13.
The repair and reconstruction of bone defects remain a challenge in orthopedics. Inadequate mechanical qualities, poor biocompatibility, and insufficient osteoconductivity are some of the issues facing current bone healing materials. Better materials that can replicate the composition and functionality of natural bone, promote quick and full healing, and reduce the likelihood of rejection and infection are desperately needed. Bone tissue engineering, combining biomaterial scaffolds and pro-osteogenic drugs, provides support in the repair and regeneration of bone defects. The development of an effective scaffold for bone defect repair is an urgent clinical need. The present study investigates the feasibility of using microspheres based on α-tricalcium phosphate and fibroin as an osteoconductive matrix and a carrier for controlled local delivery of the E7BMP-2 peptide, in which the E7 domain confers a calcium chelation property, while the BMP-2 mimicking peptide induces bone formation. We prepared α-tricalcium phosphate/silk fibroin (α-TCP/SF) microspheres through a high voltage electric field based on the protocol of α-TCP/SF bone cement slurry. This α-TCP/SF microspheres-based system was designed for delivery vehicles of the modified BMP-2 peptide by the E7 domain to realize sustainable and steady release of the peptide. In vitro cell tests and the experimental model of cranial bone defects in rats were used to investigate the pro-osteogenic benefits. The results demonstrated that the E7BMP-2 peptide-bound microspheres functioned as a sustained release system for the peptide and enhanced osteogenic differentiation of bone marrow mesenchymal stem cells in rat calvarial defects. Additionally, toxicity studies showed that microspheres have good biocompatibility and safety. Thus, these E7BMP-2 peptide-bound α-TCP/SF microspheres provide a promising therapeutic strategy for the treatment of bone defects.
骨缺损的修复与重建仍是骨科领域的一项挑战。目前的骨愈合材料面临着机械性能不足、生物相容性差和骨传导性不足等问题。迫切需要能复制天然骨的组成和功能、促进快速完全愈合并降低排斥和感染可能性的更好材料。骨组织工程结合生物材料支架和促骨生成药物，为骨缺损的修复与再生提供支持。开发一种有效的骨缺损修复支架是临床的迫切需求。本研究探讨了使用基于α-磷酸三钙和丝素蛋白的微球作为骨传导基质以及E7BMP-2肽可控局部递送载体的可行性，其中E7结构域具有钙螯合特性，而BMP-2模拟肽可诱导骨形成。我们基于α-TCP/SF骨水泥浆的方案，通过高压电场制备了α-磷酸三钙/丝素蛋白（α-TCP/SF）微球。这种基于α-TCP/SF微球的系统被设计为通过E7结构域修饰的BMP-2肽的递送载体，以实现该肽的可持续稳定释放。利用体外细胞试验和大鼠颅骨缺损实验模型来研究其促骨生成益处。结果表明，结合E7BMP-2肽的微球可作为该肽的缓释系统，并增强大鼠颅骨缺损处骨髓间充质干细胞的成骨分化。此外，毒性研究表明微球具有良好的生物相容性和安全性。因此，这些结合E7BMP-2肽的α-TCP/SF微球为骨缺损治疗提供了一种有前景的治疗策略。
