Self-Adhesive Hydrogel Biomimetic Periosteum to Promote Critical-Size Bone Defect Repair via Synergistic Osteogenesis and Angiogenesis.
Self-Adhesive Hydrogel Biomimetic Periosteum to Promote Critical-Size Bone Defect Repair via Synergistic Osteogenesis and Angiogenesis.
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DOI：
10.1021/acsami.2c08400
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发表时间：
2022-08
影响因子：
9.5
通讯作者：
Zhen Yang;Zhengyu Yang;L. Ding;Peng Zhang;Cong Liu;Dafu Chen;Fujian Zhao;Gang Wang;Xiaofeng Chen
中科院分区：
文献类型：
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作者：
Zhen Yang;Zhengyu Yang;L. Ding;Peng Zhang;Cong Liu;Dafu Chen;Fujian Zhao;Gang Wang;Xiaofeng Chen
骨膜具有募集多种细胞、促进血管网重建、引导骨组织再生等功能，在临界尺寸骨缺损的再生中起着重要作用。然而，这些功能不能通过简单地经由材料结构设计模拟骨膜或通过加载外源性细胞因子来容易地实现。在此，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来增强天然聚合物水凝胶膜。采用多巴胺改性明胶和氧化透明质酸（GA/HA）制备具有骨组织自粘附功能的仿生骨膜，并将微/纳米生物活性玻璃（MNBG）进一步掺入水凝胶中，制备有机/无机共交联水凝胶膜（GA/HA-BG）。MNBG的加入增强了天然聚合物水凝胶膜的稳定性，导致持续的降解时间、生物矿化和离子的长期释放。生物活性玻璃释放的Ca 2+和SiO 44-离子被证明可以募集细胞并促进骨髓基质细胞向成骨细胞分化，启动多中心成骨行为。此外，生物活性离子能够通过PI 3 K/Akt/HIF-1α途径持续刺激人脐静脉内皮细胞内源性表达血管内皮生长因子，加速缺损区血管化，协同促进骨缺损修复。这种有机-无机仿生骨膜已被证明是有效的和通用的临界尺寸的骨缺损修复，并有望为解决临床问题提供一个有前途的策略。
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 Ca2+ and SiO44- 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.