Department of Biomedical Engineering, University of California, Davis, California 95616, United States.
Davidson School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
ACS Biomater Sci Eng. 2024 May 13;10(5):3242-3254. doi: 10.1021/acsbiomaterials.4c00200. Epub 2024 Apr 17.
Osteoarthritis is characterized by enzymatic breakdown of the articular cartilage via the disruption of chondrocyte homeostasis, ultimately resulting in the destruction of the articular surface. Decades of research have highlighted the importance of inflammation in osteoarthritis progression, with inflammatory cytokines shifting resident chondrocytes into a pro-catabolic state. Inflammation can result in poor outcomes for cells implanted for cartilage regeneration. Therefore, a method to promote the growth of new cartilage and protect the implanted cells from the pro-inflammatory cytokines found in the joint space is required. In this study, we fabricate two gel types: polymer network hydrogels composed of chondroitin sulfate and hyaluronic acid, glycosaminoglycans (GAGs) known for their anti-inflammatory and prochondrogenic activity, and interpenetrating networks of GAGs and collagen I. Compared to a collagen-only hydrogel, which does not provide an anti-inflammatory stimulus, chondrocytes in GAG hydrogels result in reduced production of pro-inflammatory cytokines and enzymes as well as preservation of collagen II and aggrecan expression. Overall, GAG-based hydrogels have the potential to promote cartilage regeneration under pro-inflammatory conditions. Further, the data have implications for the use of GAGs to generally support tissue engineering in pro-inflammatory environments.
骨关节炎的特征是通过破坏软骨细胞的动态平衡，使软骨细胞中的酶对关节软骨进行分解，最终导致关节表面的破坏。数十年来的研究强调了炎症在骨关节炎进展中的重要性，炎症细胞因子使常驻软骨细胞进入促分解代谢状态。炎症会对用于软骨再生的细胞产生不良后果。因此，需要一种方法来促进新软骨的生长，并保护植入细胞免受关节腔内的促炎细胞因子的影响。在这项研究中，我们制备了两种凝胶类型：由硫酸软骨素和透明质酸组成的聚合物网络水凝胶，这些糖胺聚糖（GAGs）因其抗炎和促软骨形成活性而闻名，以及 GAGs 和 I 型胶原的互穿网络。与不提供抗炎刺激的仅含胶原的水凝胶相比，GAG 水凝胶中的软骨细胞导致促炎细胞因子和酶的产生减少，同时保持 II 型胶原和聚集蛋白聚糖的表达。总的来说，基于 GAG 的水凝胶有可能在促炎条件下促进软骨再生。此外，这些数据对于使用 GAG 来普遍支持促炎环境中的组织工程具有重要意义。
