Shear-thinning hyaluronan-based fluid hydrogels to modulate viscoelastic properties of osteoarthritis synovial fluids
Shear-thinning hyaluronan-based fluid hydrogels to modulate viscoelastic properties of osteoarthritis synovial fluids
复制标题
基于剪切稀化透明质酸的流体水凝胶调节骨关节炎滑液的粘弹性
DOI：
10.1039/c9bm00298g
复制
发表时间：
2019-08-01
影响因子：
6.6
通讯作者：
Fu, Ailing
中科院分区：
文献类型：
--
作者：
Cai, Zhixiang;Zhang, Hongbin;Fu, Ailing
透明质酸（透明质酸，HA）由于其独特的生理特性，已被广泛探索为生物医学和制药应用中有吸引力的生物材料。特别地，HA是正常膝关节滑液的主要成分，并为滑液提供粘弹性。在骨关节炎关节中，滑液失去其独特的粘弹性和润滑特性。据信，在患有骨关节炎的膝关节中进行关节内注射HA可以恢复滑液的粘弹性和润滑能力。然而，HA 的主要缺点是它在滑液中快速降解。为了克服HA快速清除的问题，本研究合成了一种基于HA的水凝胶（由二硫醇封端的聚乙二醇交联的乙烯基砜修饰的HA，HA-VS/SH-2-PEG）。然后通过将HA-VS/SH-2-PEG微凝胶添加到HA溶液中来制备具有可调粘弹性和可控降解速率的可注射液体水凝胶（粘性补充剂）。所得的粘性补充剂表现出增强的粘弹性、润滑作用、有效的曲安奈德有效负载能力、对酶降解的高抵抗力以及良好的生物相容性和抑制体内骨关节炎进展的能力。总体而言，这些结果为使用可注射流体水凝胶作为治疗骨关节炎的策略提供了支持，并具有临床转化的潜力。
Hyaluronan (hyaluronic acid, HA) has been extensively explored as an attractive biomaterial for biomedical and pharmaceutical applications due to its unique physiological properties. In particular, HA is a major component of synovial fluid in normal knee joints and provides viscoelastic properties to synovial fluid. In osteoarthritic joints, synovial fluid loses its unique viscoelastic and lubrication properties. Intra-articular injection of HA in osteoarthritic knee joints is believed to restore viscoelasticity and lubrication abilities to synovial fluid. However, the main drawback of HA is its rapid degradation in synovial fluid. In order to overcome the problem of rapid clearance of HA, a HA-based hydrogel (vinyl sulfone-modified HA crosslinked by dithiol-terminated poly(ethylene glycol), HA-VS/SH-2-PEG) was synthesized in this study. Injectable fluid hydrogels (viscosupplements) possessing tunable viscoelasticity and controllable degradation rates were then prepared by adding HA-VS/SH-2-PEG microgels to HA solutions. The resultant viscosupplements exhibit enhanced viscoelastic properties, lubrication effects, efficient triamcinolone acetonide payload capacity, and high resistance to enzymatic degradation along with good biocompatibility and the capability to inhibit the progression of osteoarthritis in vivo. Overall, the results provide support for the use of injectable fluid hydrogels as a strategy for the treatment of osteoarthritis and potential for the clinical translation.