Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710049, China.
School of Chemistry, Xi'an Jiaotong University, Xi'an, 710049, China.
Nat Commun. 2023 Nov 27;14(1):7771. doi: 10.1038/s41467-023-43334-8.
Osteoarthritis is a worldwide prevalent disease that imposes a significant socioeconomic burden on individuals and healthcare systems. Achieving cartilage regeneration in patients with osteoarthritis remains challenging clinically. In this work, we construct a multiple hydrogen-bond crosslinked hydrogel loaded with tannic acid and Kartogenin by polyaddition reaction as a cell-free scaffold for in vivo cartilage regeneration, which features ultra-durable mechanical properties and stage-dependent drug release behavior. We demonstrate that the hydrogel can withstand 28000 loading-unloading mechanical cycles and exhibits fast shape memory at body temperature (30 s) with the potential for minimally invasive surgery. We find that the hydrogel can also alleviate the inflammatory reaction and regulate oxidative stress in situ to establish a microenvironment conducive to healing. We show that the sequential release of tannic acid and Kartogenin can promote the migration of bone marrow mesenchymal stem cells into the hydrogel scaffold, followed by the induction of chondrocyte differentiation, thus leading to full-thickness cartilage regeneration in vivo. This work may provide a promising solution to address the problem of cartilage regeneration.
骨关节炎是一种全球性的多发病，给个人和医疗体系带来了巨大的社会经济负担。临床上，实现骨关节炎患者的软骨再生仍然具有挑战性。在这项工作中，我们通过加聚反应构建了一种具有超耐用机械性能和时变药物释放行为的负载单宁酸和卡托金的多重氢键交联水凝胶，作为无细胞支架用于体内软骨再生。我们证明了该水凝胶可以承受 28000 次加载-卸载机械循环，并且在体温（30 秒）下具有快速形状记忆功能，具有微创外科手术的潜力。我们发现，水凝胶还可以减轻炎症反应并在原位调节氧化应激，从而建立有利于愈合的微环境。我们表明，单宁酸和卡托金的顺序释放可以促进骨髓间充质干细胞向水凝胶支架内迁移，随后诱导软骨细胞分化，从而导致体内全层软骨再生。这项工作可能为解决软骨再生问题提供了一种有前途的解决方案。
