Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
J Mater Chem B. 2019 Mar 14;7(10):1716-1725. doi: 10.1039/c8tb01664j. Epub 2018 Oct 8.
Gelatin methacryloyl (GelMA) hydrogels are widely used for tissue regeneration. Nonetheless, a pure GelMA hydrogel cannot efficiently serve for cartilage regeneration because of weak mechanical properties and brittleness. In this study, we established a mussel-inspired strategy for tuning the mechanical properties of GelMA hydrogels by intercalating oligomers of dopamine methacrylate (ODMA) into the chain of GelMA. After the ODMA intercalated, the hydrogel became tough and resilient. This is because ODMA intercalation reduces the high density of entangled GelMA chains and introduces additional sacrificial physical cross-linking into the hydrogel. Rheological analysis showed that the ODMA-GelMA hydrogel was mechanically stable at body temperature. The hydrogel also manifested a sustained protein release because of the ODMA catechol groups. Furthermore, the ODMA-GelMA hydrogel was found to have good biocompatibility and affinity for cells and tissues because of the catechol groups on ODMA. In vitro, the hydrogel promoted mesenchymal stem cell adhesion and growth, and in vivo, it promoted cartilage regeneration after loading with chondroitin sulfate or TGF-β. The hydrogel can serve as a growth-factor-free scaffold for cartilage regeneration. This hydrogel not only provided a favorable microenvironment for cartilage repair but also could serve as a promising candidate material for repair of other tissues. This mussel-inspired strategy of introduction of reactive oligomers instead of polymers into a brittle hydrogel network may be extended to the development of other tough hydrogels for biomedical applications.
明胶甲基丙烯酰（GelMA）水凝胶广泛用于组织再生。然而，由于机械性能较弱和脆性，纯 GelMA 水凝胶不能有效地用于软骨再生。在这项研究中，我们建立了一种贻贝类策略，通过将多巴胺甲基丙烯酰胺（ODMA）的低聚物插入 GelMA 的链中，来调整 GelMA 水凝胶的机械性能。ODMA 插入后，水凝胶变得坚韧有弹性。这是因为 ODMA 插入减少了高浓度纠缠的 GelMA 链，并在水凝胶中引入了额外的牺牲物理交联。流变分析表明，ODMA-GelMA 水凝胶在体温下具有机械稳定性。由于 ODMA 儿茶酚基团，水凝胶还表现出持续的蛋白质释放。此外，由于 ODMA 上的儿茶酚基团，ODMA-GelMA 水凝胶具有良好的生物相容性和对细胞和组织的亲和力。体外，水凝胶促进间充质干细胞的黏附和生长，体内，在加载硫酸软骨素或 TGF-β 后，促进软骨再生。该水凝胶可作为无生长因子的软骨再生支架。这种水凝胶不仅为软骨修复提供了有利的微环境，而且可能成为修复其他组织的有前途的候选材料。这种将反应性低聚物而不是聚合物引入脆性水凝胶网络的贻贝类策略可能会扩展到用于生物医学应用的其他坚韧水凝胶的开发。
