He Jian, Qiao Liang, Fu Qizhi, Zhang Xiangchun, Liu Jiayu, Li Sanqiang, Hu Xulin
College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, China.
Henan Univ Sci & Technol, Affiliated Hosp 1, Key Lab Neuromol Biol, Coll Clin Med, Luoyang 471003, China.
J Control Release. 2025 Aug 5;386:114097. doi: 10.1016/j.jconrel.2025.114097.
Conventional bone grafts face challenges in clinical applications, including donor shortages, immunological rejection, and mismatched degradation rates. This work introduces a porous microsphere scaffold loaded with self-assembled tea polyphenolic‑magnesium biomineralized nanoparticles to synergistically enhance antibacterial and osteogenic properties through a dual-factor spatiotemporal controlled release approach. Employing a biomimetic mineralization mechanism that mimics natural bone mineral formation, these nanoparticles integrate tea polyphenols with magnesium ions. This method achieves pH-responsive release kinetics: the antimicrobial component releases more effectively in mildly acidic infection microenvironments, while the mineral phase acts as a buffer against burst release, maintaining consistent local medication concentrations. Complementing this sustained-release behavior, polytrimethylene carbonate microspheres degrade via surface erosion, thereby extending therapeutic efficacy through dual "degradation-release" regulation. In vitro studies demonstrated effective eradication of methicillin-resistant Staphylococcus aureus biofilms, along with significant enhancement of osteoblast proliferation, differentiation, and mineralization activities by the scaffold. The scaffold's porous structure mimics cancellous bone, providing an appropriate compression modulus (∼195 MPa), supporting cell infiltration, and facilitating nutrient transport, thereby simulating the three-dimensional architecture of native bone tissue. Moreover, the scaffold modulates macrophage polarization toward the M2 phenotype and stimulates the secretion of anti-inflammatory cytokines (IL-37, IL-10), thereby fostering a favorable bone immune microenvironment. This work establishes a multifunctional bone tissue engineering platform by integrating spatiotemporal delivery (dual controlled release) with biomimetic mineral stabilization. By addressing infection control, promoting bone regeneration, and modulating immune responses simultaneously, this scaffold presents a promising solution for complicated infected bone defects.
传统骨移植在临床应用中面临诸多挑战，包括供体短缺、免疫排斥和降解速率不匹配等问题。本研究引入了一种负载自组装茶多酚 - 镁生物矿化纳米颗粒的多孔微球支架，通过双因素时空控释方法协同增强抗菌和成骨性能。这些纳米颗粒采用模拟天然骨矿物质形成的仿生矿化机制，将茶多酚与镁离子整合在一起。该方法实现了pH响应释放动力学：抗菌成分在轻度酸性感染微环境中更有效地释放，而矿相作为防止突发释放的缓冲剂，维持局部药物浓度的一致性。作为这种持续释放行为的补充，聚碳酸三亚甲基酯微球通过表面侵蚀降解，从而通过双重“降解 - 释放”调节延长治疗效果。体外研究表明，该支架能有效根除耐甲氧西林金黄色葡萄球菌生物膜，同时显著增强成骨细胞的增殖、分化和矿化活性。该支架的多孔结构模仿松质骨，提供了合适的压缩模量（约195MPa），支持细胞浸润并促进营养物质运输，从而模拟天然骨组织的三维结构。此外，该支架调节巨噬细胞向M2表型极化，并刺激抗炎细胞因子（IL - 37、IL - 10）的分泌，从而营造有利的骨免疫微环境。本研究通过将时空递送（双重控释）与仿生矿化稳定化相结合，建立了一个多功能骨组织工程平台。通过同时解决感染控制、促进骨再生和调节免疫反应，该支架为复杂的感染性骨缺损提供了一种有前景的解决方案。
