Zhuang Yu, Wu Dingwei, Zhou Lvyang, Liu Boyuan, Zhao Xingkai, Yang Jianmin, Liu Wenge, Wang Zhenyu, Zheng Yunquan, Shi Xianai
College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China.
Fujian Key Laboratory of Medical Instrument and Pharmaceutical Technology, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China.
ACS Biomater Sci Eng. 2025 Mar 10;11(3):1690-1704. doi: 10.1021/acsbiomaterials.4c02095. Epub 2025 Feb 5.
The inadequate vascularization and abnormal immune microenvironment in the diabetic bone defect region present a significant challenge to osteogenic regulation. Inspired by the distinctive characteristics of healing staged in diabetic bone defects and the structure-function relationship in the natural periosteum, we fabricated an electrospun bilayer biomimetic periosteum (Bilayer@E) to promote regeneration of diabetic bone defects. Here, the inner layer of biomimetic periosteum was fabricated using coaxial electrospinning fibers, with a shell incorporating zinc oxide nanoparticles (ZnO NPs) and a core containing silicon dioxide nanoparticles (SiO NPs) mimicking the cambium of periosteum; the outer layer consisted of randomly aligned electrospun fibers loaded with deferoxamine (DFO), simulating the fibrous layer of periosteum; finally, epigallocatechin-3-gallate (EGCG) was coated onto the bilayer membrane to obtain Bilayer@E. The presence of EGCG on the Bilayer@E surface efficiently triggers a phenotypic transition in macrophages, shifting them from an M1 proinflammatory state to an M2 anti-inflammatory state. Moreover, the sequential release of ZnO NPs, DFO, and SiO NPs exhibits antimicrobial characteristics while coordinating angiogenesis and promoting osteogenic mineralization in cells. Importantly, the biomimetic periosteum shows strong bone tissue and periosteal regeneration properties in diabetic rats. The integration of sequential drug release and immunomodulation, tailored to meet the specific healing requirements during bone regeneration, offers new insights for advancing the application of biomaterials in this field.
糖尿病骨缺损区域血管化不足和免疫微环境异常，对成骨调节构成了重大挑战。受糖尿病骨缺损愈合阶段的独特特征以及天然骨膜结构 - 功能关系的启发，我们制备了一种静电纺丝双层仿生骨膜（Bilayer@E），以促进糖尿病骨缺损的再生。在此，仿生骨膜的内层采用同轴静电纺丝纤维制成，外壳包含氧化锌纳米颗粒（ZnO NPs），核心含有二氧化硅纳米颗粒（SiO NPs），模拟骨膜的形成层；外层由负载去铁胺（DFO）的随机排列静电纺丝纤维组成，模拟骨膜的纤维层；最后，将表没食子儿茶素 - 3 - 没食子酸酯（EGCG）涂覆在双层膜上，得到Bilayer@E。Bilayer@E表面的EGCG能够有效触发巨噬细胞的表型转变，使其从M1促炎状态转变为M2抗炎状态。此外，ZnO NPs、DFO和SiO NPs的顺序释放具有抗菌特性，同时能协调血管生成并促进细胞中的成骨矿化。重要的是，这种仿生骨膜在糖尿病大鼠中表现出强大的骨组织和骨膜再生特性。顺序药物释放与免疫调节的结合，是为满足骨再生过程中的特定愈合需求而量身定制的，为推进生物材料在该领域的应用提供了新的见解。
