Intraarticularly injectable silk hydrogel microspheres with enhanced mechanical and structural stability to attenuate osteoarthritis.
Intraarticularly injectable silk hydrogel microspheres with enhanced mechanical and structural stability to attenuate osteoarthritis.
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DOI：
10.1016/j.biomaterials.2022.121611
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发表时间：
2022-05
期刊：
影响因子：
14
通讯作者：
Tao Wang;Yuqi Li;Jian Liu;Y. Fang;Wen-jun Guo;Yu Liu;Xiangyu Li;Gang Li;Xiuli Wang
中科院分区：
文献类型：
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作者：
Tao Wang;Yuqi Li;Jian Liu;Y. Fang;Wen-jun Guo;Yu Liu;Xiangyu Li;Gang Li;Xiuli Wang
利用二缩水甘油醚(BDDE)制备了丝素蛋白(丝素)水凝胶，二缩水甘油醚是一种化学交联剂，通常用于生产食品和药物管理局(FDA)批准的透明质酸(HA)医疗产品。所制得的蚕丝/BDDE水凝胶具有较高的弹性(压缩模数为166±15.0 kPa)、抗疲劳性能以及在水溶液中稳定的结构和机械强度。化学交联是在高浓度(9.3微米)的溴化锂溶液中进行的，溴化锂是一种盐，在丝绸增溶过程中通常用于溶解脱胶真丝纤维。在这些反应条件下，丝素分子的展开和延伸结构，以及溴化锂提供的独特离子环境，促进了水凝胶的高度交联性。当将蚕丝溶解在其他蚕丝纤维溶解试剂(如味泽氏溶液、甲酸/溴化锂溶液、FA/CaCl2溶液)中时，没有得到类似的水凝胶，这可能是因为部分折叠的蚕丝结构和这些试剂的离子条件不利于交联反应。基于这些发现，采用油/水(O/W)乳化方法制备了蚕丝/BDDE水凝胶微球，并与其他丝胶控制系统(如酶催化二酪氨酸和不规则形状的丝粉/BDDE凝胶颗粒)一起，在体内评价了生物相容性和生物降解性。组织学和免疫组织化学分析表明，丝素/BDDE水凝胶微球具有良好的生物相容性，可作为生物润滑剂用于骨关节炎的治疗。关节内注射凝胶球减轻了OA大鼠的疼痛，减少了软骨损伤，并在更长的时间范围内抵抗了关节腔内的消化环境(>；4周)，这表明在未来的OA治疗中对缓解疼痛和持续药物释放是有效的。
A silk fibroin (silk) hydrogel was prepared by using diglycidyl ether (BDDE), a chemical crosslinker commonly used to generate Food and Drug Administration (FDA)-approved hyaluronic acid (HA) medical products. The silk/BDDE hydrogels exhibited high elasticity (compressive modulus of 166 ± 15.0 kPa), anti-fatigue properties, and stable structure and mechanical strength in aqueous solution. Chemical crosslinking was conducted in a high concentration (9.3 M) of lithium bromide (LiBr) solution, a salt that is commonly used to dissolve degummed silk fibers during silk solubilization. The unfolded and extended structure of silk molecules with these reaction conditions, as well as the unique ionic environment provided by LiBr facilitated a high degree of crosslinking in the hydrogel. Similar hydrogels were not obtained when the silk was dissolved in other silk fiber-dissolving reagents (e.g., Ajisawa's, formic acid (FA)/LiBr, FA/CaCl2solutions), likely because partially folded silk structures and the ionic conditions with these reagents were less favorable for the crosslinking reaction. Based on these findings, silk/BDDE hydrogel spheres were prepared using an oil/water (o/w) emulsification method and biocompatibility and biodegradation were evaluatedin vivo, along with other silk gel control systems (e.g., enzyme-catalyzed di-tyrosine and pulverized silk/BDDE gel particles with irregular shapes). Histological and immunohistochemical analyses demonstrated that the silk/BDDE hydrogel spheres were biocompatible and served as a bio-lubricant to treat osteoarthritis (OA). The intra-articular injection of the gel spheres reduced pain as measured with OA rats, reduced cartilage damage and resisted the digestive environment in the articular cavity for extended time frames (>4 weeks), suggesting utility for pain relief and sustained drug release for future OA treatments.