An injectable and thermosensitive hydrogel: Promoting periodontal regeneration by controlled-release of aspirin and erythropoietin
An injectable and thermosensitive hydrogel: Promoting periodontal regeneration by controlled-release of aspirin and erythropoietin
复制标题
可注射的热敏水凝胶：通过控制释放阿司匹林和促红细胞生成素促进牙周再生
DOI：
10.1016/j.actbio.2019.01.001
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发表时间：
2019-03-01
影响因子：
9.7
通讯作者：
Sun, Hongchen
中科院分区：
文献类型：
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作者：
Xu, Xiaowei;Gu, Zhongyi;Sun, Hongchen
牙周炎是由宿主免疫系统和菌斑微生物之间复杂的相互作用引起的炎症性疾病。牙周炎引起的牙槽骨吸收被认为是成年人牙齿缺失的主要原因之一。要终止牙槽骨吸收，需要同时抗炎和牙周组织再生，这在现有的方法中还没有出现。本研究以壳聚糖（CS）、β-甘油磷酸钠（beta-GP）和明胶为原料，制备了一种可注射的温敏性水凝胶，该水凝胶可持续释放阿司匹林和促红细胞生成素（EPO），分别发挥抗炎和组织再生的药理作用。结果表明，阿司匹林和EPO在该水凝胶中可持续释放21 d以上，且在体内外均无毒性。免疫组织化学染色和micro-CT分析表明，施用载有阿司匹林/EPO的CS/β-GP/明胶水凝胶可以终止炎症并恢复牙槽骨的高度，这通过组织学观察进一步证实。结果表明，CS/beta-GP/gelatin水凝胶具有良好的生物相容性，可作为载药载体制备，且载药后的CS/beta-GP/gelatin水凝胶具有良好的抗炎和牙周组织再生作用，为牙周炎的治疗提供了一种潜在的药物载体。需要同时抗炎和牙周组织再生，这在现有方法中还没有出现。在此，（1）负载阿司匹林/促红细胞生成素（EPO）的壳聚糖（CS）/β-甘油磷酸钠/明胶水凝胶可在体温下5 min内形成，具有良好的体内外生物相容性;（2）阿司匹林在早期比EPO更快的释放有利于抗炎，并为后续步骤中保证EPO的再生功能提供了微环境。体内实验表明，该水凝胶可有效控制牙周组织的炎症和再生。这些结果表明我们合成的水凝胶在未来的临床应用中具有很大的潜力。(C)2019 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Periodontitis is an inflammatory disease induced by complex interactions between host immune system and plaque microorganism. Alveolar bone resorption caused by periodontitis is considered to be one of the main reasons for tooth loss in adults. To terminate the alveolar bone resorption, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. In this study, chitosan (CS), beta-sodium glycerophosphate (beta-GP), and gelatin were used to prepare an injectable and thermosensitive hydrogel, which could continuously release aspirin and erythropoietin (EPO) to exert pharmacological effects of anti-inflammation and tissue regeneration, respectively. The releasing profile showed that aspirin and EPO could be continuously released from the hydrogels, which exhibited no toxicity both in vitro and in vivo, for at least 21 days. Immunohistochemistry staining and micro-CT analyses indicated that administration of CS/beta-GP/gelatin hydrogels loaded with aspirin/EPO could terminate the inflammation and recover the height of the alveolar bone, which is further confirmed by histological observations. Our results suggested that CS/beta-GP/gelatin hydrogels are easily prepared as drug-loading vectors with excellent biocompatibility, and the CS/beta-GP/gelatin hydrogels loaded with aspirin/EPO are quite effective in anti-inflammation and periodontium regeneration, which provides a great potential candidate for periodontitis treatment in the dental clinic.Statement of SignificanceTo terminate the alveolar bone resorption caused by periodontitis, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. Here, (1) the chitosan (CS)/beta-sodium glycerophosphate/gelatin hydrogels loaded with aspirin/erythropoietin (EPO) can form at body temperature in 5 min with excellent biocompatibility in vitro and in vivo; (2) The faster release of aspirin than EPO in the early stage is beneficial for anti-inflammation and provides a microenvironment for ensuring the regeneration function of EPO in the following step. In vivo experiments revealed that the hydrogels are effective in the control of inflammation and regeneration of the periodontium. These results indicate that our synthesized hydrogels have a great potential in the future clinical application. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.