Wu Dongze, Yang Shuhui, Gong Zhe, Zhu Xinxin, Hong Juncong, Wang Haitao, Xu Wenbin, Lai Juncheng, Wang Xiumei, Lu Jiye, Fang Xiangqian, Jiang Guoqiang, Zhu Jinjin
Department of Spinal Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, Zhejiang, China.
School of Materials Science and Engineering, Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, Zhejiang, China.
Mater Today Bio. 2024 Nov 21;29:101353. doi: 10.1016/j.mtbio.2024.101353. eCollection 2024 Dec.
Osteoarthritis (OA) is characterized by symptoms such as abnormal lubrication function of synovial fluid and heightened friction on the cartilage surface in its early stages, prior to evident cartilage damage. Current early intervention strategies employing lubricated hydrogels to shield cartilage from friction often overlook the significance of hydrogel-cartilage adhesion and enhancement of the cartilage extracellular matrix (ECM). Herein, we constructed a hydrogel based on dihydrazide-modified hyaluronic acid (HA) (AHA) and catechol-conjugated aldehyde-modified HA (CHA), which not only adheres to the cartilage surface as an effective lubricant but also improves the extracellular environment of chondrocytes in OA. Material characterization experiments on AHA/CHA hydrogels with varying concentrations validated their exceptional self-healing capabilities, superior injectability and viscoelasticity, sustained adhesion strength to cartilage, and a low friction coefficient. Chondrocytes exhibited robust adhesion and proliferation on the AHA/CHA hydrogel surface, with the upregulation of cartilage matrix protein expression. Intra-articular injection of AHA/CHA hydrogels was performed following destabilization of the medial meniscus (DMM) surgery in mice to assess its protective effect on cartilage. The AHA/CHA hydrogel effectively attenuated the degree of cartilage wear, facilitated chondrocytes' anabolic metabolism, and restored the ECM of cartilage. Therefore, the AHA/CHA hydrogel emerges as a promising therapeutic approach in clinical practices of OA treatment.
骨关节炎（OA）的特征在于，在明显的软骨损伤之前，其早期阶段会出现诸如滑液润滑功能异常和软骨表面摩擦力增加等症状。目前采用润滑水凝胶来保护软骨免受摩擦的早期干预策略往往忽视了水凝胶与软骨的粘附以及软骨细胞外基质（ECM）增强的重要性。在此，我们构建了一种基于二酰肼修饰透明质酸（HA）（AHA）和儿茶酚共轭醛修饰HA（CHA）的水凝胶，它不仅作为一种有效的润滑剂粘附在软骨表面，而且还改善了骨关节炎中软骨细胞的细胞外环境。对不同浓度的AHA/CHA水凝胶进行的材料表征实验证实了它们具有出色的自愈能力、卓越的可注射性和粘弹性、对软骨的持续粘附强度以及低摩擦系数。软骨细胞在AHA/CHA水凝胶表面表现出强大的粘附和增殖能力，同时软骨基质蛋白表达上调。在小鼠内侧半月板不稳定（DMM）手术后进行关节内注射AHA/CHA水凝胶，以评估其对软骨的保护作用。AHA/CHA水凝胶有效减轻了软骨磨损程度，促进了软骨细胞的合成代谢，并恢复了软骨的ECM。因此，AHA/CHA水凝胶在骨关节炎治疗的临床实践中成为一种有前景的治疗方法。
