School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China.
National Engineering Research Centre for Tissue Restoration and Reconstruction, Guangzhou 510006, China.
ACS Appl Mater Interfaces. 2022 Aug 17;14(32):36395-36410. doi: 10.1021/acsami.2c08400. Epub 2022 Aug 4.
The periosteum plays an important role in the regeneration of critical-size bone defects, with functions of recruiting multiple cells, accelerating vascular network reconstruction, and guiding bone tissue regeneration. However, these functions cannot be easily implemented by simply simulating the periosteum via a material structure design or by loading exogenous cytokines. Herein, inspired by the periosteal function, we propose a biomimetic periosteum preparation strategy to enhance natural polymer hydrogel membranes using inorganic bioactive materials. The biomimetic periosteum having bone tissue self-adhesive functions and resembling an extracellular matrix was prepared using dopamine-modified gelatin and oxidized hyaluronan (GA/HA), and micro/nanobioactive glass (MNBG) was further incorporated into the hydrogel to fabricate an organic/inorganic co-crosslinked hydrogel membrane (GA/HA-BG). The addition of MNBG enhanced the stability of the natural polymer hydrogel membrane, resulting in a sustained degradation time, biomineralization, and long-term release of ions. The Ca and SiO ions released by bioactive glass were shown to recruit cells and promote the differentiation of bone marrow stromal cells into osteoblasts, initiating multicentric osteogenic behavior. Additionally, the bioactive ions were able to continuously stimulate the endogenous expression of vascular endothelial growth factor from human umbilical vein endothelial cells through the PI3K/Akt/HIF-1α pathway, which accelerated vascularization of the defect area and synergistically promoted the repair of bone defects. This organic-inorganic biomimetic periosteum has been proved to be effective and versatile in critical-size bone defect repair and is expected to provide a promising strategy for solving clinical issues.
骨膜在临界尺寸骨缺损的再生中起着重要作用，具有募集多种细胞、加速血管网络重建和指导骨组织再生的功能。然而，这些功能不能简单地通过模拟骨膜的材料结构设计或加载外源性细胞因子来实现。受骨膜功能的启发，我们提出了一种仿生骨膜制备策略，使用无机生物活性材料增强天然聚合物水凝胶膜。通过多巴胺修饰的明胶和氧化透明质酸（GA/HA）制备具有骨组织自粘功能且类似于细胞外基质的仿生骨膜，并进一步将微/纳米生物活性玻璃（MNBG）掺入水凝胶中以制备有机/无机共交联水凝胶膜（GA/HA-BG）。MNBG 的添加增强了天然聚合物水凝胶膜的稳定性，从而延长了降解时间、生物矿化和离子的长期释放。生物活性玻璃释放的 Ca 和 SiO 离子能够募集细胞并促进骨髓基质细胞向成骨细胞分化，从而引发多中心成骨行为。此外，生物活性离子能够通过 PI3K/Akt/HIF-1α 通路持续刺激人脐静脉内皮细胞中血管内皮生长因子的内源性表达，加速缺损区域的血管化，并协同促进骨缺损的修复。这种有机-无机仿生骨膜已被证明在临界尺寸骨缺损修复中是有效且多功能的，有望为解决临床问题提供一种有前途的策略。
