Gelatin-CaO2/SAP/PLGA composite scaffold enhances the reparation of critical-sized cranial defects by promoting seed cell survival
Gelatin-CaO2/SAP/PLGA composite scaffold enhances the reparation of critical-sized cranial defects by promoting seed cell survival
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DOI：
10.1016/j.apmt.2021.100960
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发表时间：
2021-03
影响因子：
8.3
通讯作者：
Zhiming Zhang;Zijie Rong;Guofeng Wu;Yihan Wang;Zhiwen Tan;Juan Zheng;Yanglei Jin;Zhihao Liang;Chun Liu;Jiasong Guo;Lixin Zhu
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文献类型：
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作者：
Zhiming Zhang;Zijie Rong;Guofeng Wu;Yihan Wang;Zhiwen Tan;Juan Zheng;Yanglei Jin;Zhihao Liang;Chun Liu;Jiasong Guo;Lixin Zhu
氧供应不足是骨组织工程修复骨缺损的最大障碍之一，特别是在移植初期，氧供应不足对种子细胞在支架中的存活有着极其不利的影响。在此，我们设计了一种可控产氧复合支架，消除了这一限制。这种产氧复合支架由过氧化钙（CaO 2）释放微粒，水凝胶和聚（乳酸-羟基乙酸共聚物（PLGA）膜组成。由明胶和CaO 2组成的微粒在与水接触时被水解活化以产生氧气。水凝胶，自组装肽（SAP），和PLGA膜的设计，以防止明胶-氧化钙微球直接暴露于大量的水，并提供一个三维环境的细胞生长。该产氧复合支架在体外和体内分别可持续控制约21天和28天的氧生成。使用外周血来源的间充质干细胞和临界尺寸的颅骨缺损测试这种产氧复合支架改善种子细胞存活和修复骨缺损的能力。与对照组相比，与生氧微球共培养或共移植的种子细胞在体外和体内的存活率均显著提高。明胶-CaO 2微球的存在显著改善了骨缺损的修复。这些结果表明，本研究中的产氧复合支架具有很大的潜力，以增加种子细胞的存活和促进骨缺损的重建。
One of the most hindrance for bone tissue engineering to reconstruct a bone defect is that the insufficient oxygen supply, which has an extremely negative influence upon the survival of seed cells in the scaffold, especially during the initial transplantation period. Herein, we devised a controlled-oxygen-generating composite scaffold that removes this limitation. This oxygen-generating composite scaffold consists of calcium peroxide (CaO2)-releasing microparticles, hydrogel, and a poly(lactic-co-glycolic acid (PLGA) membrane. The microparticles, which are composed of gelatin and CaO2, are hydrolytically activated to generate oxygen when they make contact with water. The hydrogel, self-assembling peptide(SAP), and PLGA membrane were designed to prevent direct exposure of the gelatin-CaO2microspheres to a large quantity of water and provide a three-dimensional environment for cell growth. The oxygen-generating composite scaffold has the capability of sustainably controlling oxygen generation for about 21 daysin vitroand 28 daysin vivo. The capacities of this oxygen-generating composite scaffold to improve seed cell survival and the reparation of bone defects were tested using peripheral blood-derived mesenchymal stem cells and a critical-sized cranial defect. Compared with the control groups, survival of seed cells bothin vitroandin vivowas significantly improved when the cells were co-cultured or co-transplanted with the oxygen-generating microspheres. Moreover, the presence of the gelatin-CaO2microspheres significantly improved the repair of bone defects. These results indicated that the oxygen-generating composite scaffold in this study has great potential to increase seed cell survival and enhance bone defect reconstruction.