Highly tunable bioactive fiber-reinforced hydrogel for guided bone regeneration
Highly tunable bioactive fiber-reinforced hydrogel for guided bone regeneration
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DOI：
10.1016/j.actbio.2020.06.011
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发表时间：
2020-09-01
影响因子：
9.7
通讯作者：
Bottino, Marco C.
中科院分区：
文献类型：
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作者：
Dubey, Nileshkumar;Ferreira, Jessica A.;Bottino, Marco C.
影响牙齿周围软硬组织健康的最具破坏性的病理之一是牙周炎。在临床上，牙周组织破坏已通过综合方法进行管理，包括消除受损组织，然后采用骨替代物和/或屏障膜进行再生策略。令人遗憾的是，尚未建立具有可预测的机械完整性和多功能治疗特征的屏障膜。在本文中，我们报告了一种纤维增强水凝胶，其在机械能力和治疗特征方面具有前所未有的可调性，其通过将具有良好控制的3D结构的高度多孔聚（e-己内酯）纤维网整合到生物活性无定形磷酸镁负载的明胶甲基丙烯酰水凝胶中。无定形磷酸镁和PCL网在水凝胶中的存在可以控制机械性能并提高成骨能力，为引导骨再生（GBR）打开了巨大的机会。结果表明，通过熔融电写入制造的PCL网片的存在可以延迟水凝胶降解，防止软组织侵入，并提供机械屏障，以允许较慢迁移的祖细胞有时间参与骨再生，因为它们能够分化成骨形成细胞。总之，我们的方法提供了一个平台技术的下一代GBR膜的发展与可调的机械和治疗性能，以扩大骨再生在compromisedsites. Statement的重要性在这项研究中，我们开发了一种纤维增强水凝胶平台，具有前所未有的可调性的机械能力和治疗功能的引导骨再生。我们成功地将高度多孔的聚（ε-己内酯）[PCL]网整合到无定形磷酸镁负载水凝胶中。工程化水凝胶的刚度显著增强，并且这种增强效果可以通过改变PCL网格的数量和定制AMP浓度来调节。此外，纤维增强水凝胶显示出良好的细胞反应，矿化率显著提高，成骨相关基因和骨形成上调。总之，这些纤维增强膜与包埋在水凝胶中的治疗剂组合提供了一个稳健的、高度可调的平台，以不仅在牙周缺损中，而且在其他颅颌面部位中放大骨再生。(C)2020 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
One of the most damaging pathologies that affects the health of both soft and hard tissues around the tooth is periodontitis. Clinically, periodontal tissue destruction has been managed by an integrated approach involving elimination of injured tissues followed by regenerative strategies with bone substitutes and/or barrier membranes. Regrettably, a barrier membrane with predictable mechanical integrity and multifunctional therapeutic features has yet to be established. Herein, we report a fiber-reinforced hydrogel with unprecedented tunability in terms of mechanical competence and therapeutic features by integration of highly porous poly(e-caprolactone) fibrous mesh(es) with well-controlled 3D architecture into bioactive amorphous magnesium phosphate-laden gelatin methacryloyl hydrogels. The presence of amorphous magnesium phosphate and PCL mesh in the hydrogel can control the mechanical properties and improve the osteogenic ability, opening a tremendous opportunity in guided bone regeneration (GBR). Results demonstrate that the presence of PCL meshes fabricated via melt electrowriting can delay hydrogel degradation preventing soft tissue invasion and providing the mechanical barrier to allow time for slower migrating progenitor cells to participate in bone regeneration due to their ability to differentiate into bone-forming cells. Altogether, our approach offers a platform technology for the development of the next-generation of GBR membranes with tunable mechanical and therapeutic properties to amplify bone regeneration in compromised sites.Statement of SignificanceIn this study, we developed a fiber-reinforced hydrogel platform with unprecedented tunability in terms of mechanical competence and therapeutic features for guided bone regeneration. We successfully integrated highly porous poly(epsilon-caprolactone) [PCL] mesh(es) into amorphous magnesium phosphate-laden hydrogels. The stiffness of the engineered hydrogel was significantly enhanced, and this reinforcing effect could be modulated by altering the number of PCL meshes and tailoring the AMP concentration. Furthermore, the fiber-reinforced hydrogel showed favorable cellular responses, significantly higher rates of mineralization, upregulation of osteogenic-related genes and bone formation. In sum, these fiber-reinforced membranes in combination with therapeutic agent(s) embedded in the hydrogel offer a robust, highly tunable platform to amplify bone regeneration not only in periodontal defects, but also in other craniomaxillofacial sites. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.