Xu Songshan, Zhao Shaohua, Jian Yanpeng, Shao Xinwei, Han Dandan, Zhang Fan, Liang Chen, Liu Weijie, Fan Jun, Yang Zhikui, Zhou Jinge, Zhang Wenqiang, Wang Yigong
Department of Spinal Cord Surgery, Xuchang Central Hospital, Henan University of Science and Technology, Xuchang, China.
Medical Imaging Center, Xuchang Central Hospital, Henan University of Science and Technology, Xuchang, China.
Front Cell Dev Biol. 2022 Nov 24;10:1011260. doi: 10.3389/fcell.2022.1011260. eCollection 2022.
Currently, an effective repair method that can promote satisfactory cartilage regeneration is unavailable for cartilage damages owing to inevitable inflammatory erosion. Cartilage tissue engineering has revealed considerable treatment options for cartilage damages. Icariin (ICA) is a flavonoid component of with both chondrogenic and anti-inflammatory properties. In this study, we prepared an ICA/CTS hydrogel by loading ICA into chitosan (CTS) hydrogel to impart chondrogenesis and anti-inflammatory properties to the ICA/CTS hydrogel. results revealed that ICA showed sustained release kinetics from the ICA/CTS hydrogel. In addition, compared to the CTS hydrogel, the ICA/CTS hydrogel exhibited a favorable anti-inflammatory effect upon incubation with lipopolysaccharide pre-induced RAW264.7 macrophages, as indicated by the suppression of inflammatory-related cytokines (IL-6 and TNF-α). Additionally, when co-cultured with chondrocytes , the ICA/CTS hydrogel showed good cytocompatibility, accelerated chondrocyte proliferation, and enhanced chondrogenesis compared to the CTS hydrogel. Moreover, the engineered cartilage from the chondrocyte-loaded ICA/CTS hydrogel achieved stable cartilage regeneration when subcutaneously implanted in a goat model. Finally, the addition of ICA endowed the ICA/CTS hydrogel with a potent anti-inflammatory effect compared to what was observed in the CTS hydrogel, as confirmed by the attenuated IL-1β, IL-6, TNF-α, and TUNEL expression. The prepared ICA/CTS hydrogel offered an effective method of delivery for chondrogenic and anti-inflammatory agents and served as a useful platform for cartilage regeneration in an immunocompetent large animal model.
目前，由于不可避免的炎症侵蚀，对于软骨损伤而言，尚无一种能促进令人满意的软骨再生的有效修复方法。软骨组织工程已为软骨损伤揭示了相当多的治疗选择。淫羊藿苷（ICA）是一种具有软骨生成和抗炎特性的黄酮类成分。在本研究中，我们通过将ICA负载到壳聚糖（CTS）水凝胶中制备了ICA/CTS水凝胶，以使ICA/CTS水凝胶具有软骨生成和抗炎特性。结果显示ICA从ICA/CTS水凝胶中呈现出持续释放动力学。此外，与CTS水凝胶相比，ICA/CTS水凝胶在与脂多糖预诱导的RAW264.7巨噬细胞孵育时表现出良好的抗炎作用，这通过炎症相关细胞因子（IL-6和TNF-α）的抑制得以表明。另外，当与软骨细胞共培养时，与CTS水凝胶相比，ICA/CTS水凝胶表现出良好的细胞相容性，加速了软骨细胞增殖，并增强了软骨生成。此外，当将负载软骨细胞的ICA/CTS水凝胶皮下植入山羊模型时，所构建的软骨实现了稳定的软骨再生。最后，与CTS水凝胶中观察到的情况相比，ICA的添加赋予了ICA/CTS水凝胶强大的抗炎作用，这通过IL-1β、IL-6、TNF-α和TUNEL表达的减弱得以证实。所制备的ICA/CTS水凝胶为软骨生成和抗炎剂提供了一种有效的递送方法，并作为免疫健全的大型动物模型中软骨再生的有用平台。
