School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Macerata, Italy.
School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, Macerata, Italy.
J Cell Physiol. 2019 Nov;234(11):20013-20027. doi: 10.1002/jcp.28598. Epub 2019 Apr 9.
Osteoarthritis (OA), due to cartilage degeneration, is one of the leading causes of disability worldwide. Currently, there are not efficacious therapies to reverse cartilage degeneration. In this study we evaluated the potential of hybrid hydrogels, composed of a biodegradable and thermosensitive triblock copolymer cross-linked via Michael addition to thiolated hyaluronic acid, in contrasting inflammatory processes underlying OA. Hydrogels composed of different w/w % concentrations of hyaluronan were investigated for their degradation behavior and capacity to release the polysaccharide in a sustained fashion. It was found that hyaluronic acid was controllably released during network degradation with a zero-order release kinetics, and the release rate depended on cross-link density and degradation kinetics of the hydrogels. When locally administered in vivo in an OA mouse model, the hydrogels demonstrated the ability to restore, to some extent, bone remineralization, proteoglycan production, levels of Sox-9 and Runx-2. Furthermore, the downregulation of proinflammatory mediators, such as TNF-α, NFkB, and RANKL and proinflammatory cytokines was observed. In summary, the investigated hydrogel technology represents an ideal candidate for the potential encapsulation and release of drugs relevant in the field of OA. In this context, the hydrogel matrix could act in synergy with the drug, in reversing phenomena of inflammation, cartilage disruption, and bone demineralization associated with OA.
骨关节炎（OA）由于软骨退化，是全球致残的主要原因之一。目前，尚无有效的治疗方法可以逆转软骨退化。在这项研究中，我们评估了由可生物降解和温敏三嵌段共聚物通过迈克尔加成交联巯基化透明质酸组成的混合水凝胶在对抗 OA 下炎症过程的潜力。研究了不同 w/w%浓度的透明质酸组成的水凝胶的降解行为及其以持续方式释放多糖的能力。结果发现，透明质酸在网络降解过程中以零级释放动力学可控释放，释放速率取决于交联密度和水凝胶的降解动力学。当在 OA 小鼠模型中局部体内给药时，水凝胶表现出在一定程度上恢复骨矿化、糖胺聚糖产生、Sox-9 和 Runx-2 水平的能力。此外，观察到促炎介质（如 TNF-α、NFkB 和 RANKL）和促炎细胞因子的下调。总之，所研究的水凝胶技术代表了一种潜在的用于封装和释放与 OA 领域相关药物的理想候选物。在这种情况下，水凝胶基质可以与药物协同作用，逆转与 OA 相关的炎症、软骨破坏和骨脱矿化现象。
