Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India; The Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.
Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India; The Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.
Int J Biol Macromol. 2022 Jul 1;212:54-66. doi: 10.1016/j.ijbiomac.2022.05.093. Epub 2022 May 16.
Osteoarthritis (OA) is a debilitating progressive joint disease with high incidence and socioeconomic burden. However, no disease-modifying treatment is currently available for OA. Here, we report a sulfated carboxymethylcellulose-based scaffold mediated delivery of tissue inhibitor of metalloprotease 3 (Timp3) as a disease-modifying therapeutic strategy for OA. First, we chemically modified carboxymethylcellulose (CMC) to sulfated carboxymethylcellulose (sCMC) to impart native-like electrostatic interaction-based binding of cationic proteins. We then fabricated cartilage ECM mimicking sCMC-gelatin scaffolds which showed preferential binding and sustained delivery of Timp3. This scaffold-mediated delivery of Timp3 demonstrated a reduction in matrix degradation, protease expression and inflammatory markers in the goat ex vivo OA model leading to enhanced retention of cartilage ECM markers when compared to OA control. Further, similar results were obtained when sCMC-gelatin scaffolds were evaluated using human OA samples, supporting its clinical potential. Overall, the Timp3 loaded sCMC-gelatin scaffold shows potential as a treatment approach for OA.
骨关节炎（OA）是一种具有高发病率和社会经济负担的进行性关节疾病。然而，目前还没有针对 OA 的疾病修正治疗方法。在这里，我们报告了一种基于硫酸化羧甲基纤维素的支架介导的组织金属蛋白酶抑制剂 3（Timp3）传递，作为 OA 的疾病修正治疗策略。首先，我们通过化学修饰羧甲基纤维素（CMC）得到硫酸化羧甲基纤维素（sCMC），以赋予基于天然静电相互作用的阳离子蛋白的结合。然后，我们制备了模仿软骨细胞外基质的 sCMC-明胶支架，该支架显示出对 Timp3 的优先结合和持续释放。与 OA 对照组相比，这种支架介导的 Timp3 传递可减少基质降解、蛋白酶表达和炎症标志物，从而增强软骨细胞外基质标志物的保留。此外，当使用人 OA 样本评估 sCMC-明胶支架时，也得到了类似的结果，支持了其临床潜力。总的来说，负载 Timp3 的 sCMC-明胶支架具有作为 OA 治疗方法的潜力。
