Injectable Quercetin-Loaded Hydrogel with Cartilage-Protection and Immunomodulatory Properties for Articular Cartilage Repair
Injectable Quercetin-Loaded Hydrogel with Cartilage-Protection and Immunomodulatory Properties for Articular Cartilage Repair
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具有软骨保护和免疫调节特性的可注射槲皮素水凝胶，用于关节软骨修复
DOI：
10.1021/acsabm.9b00673
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发表时间：
2020
影响因子：
4.7
通讯作者：
He Yaohua
中科院分区：
文献类型：
--
作者：
Yu Weihan;Zhu Yanlun;Li Haiyan;He Yaohua
关节软骨在人体内起着重要的作用。关节软骨由于各种原因出现缺损时如何修复一直是临床上的一大难题。近年来的研究表明，减缓软骨细胞外基质（ECM）的降解和调节宿主的炎症反应从而促进软骨组织再生在软骨修复过程中是重要的。在这项研究中，载药可注射水凝胶构建用于修复关节软骨。这种水凝胶不仅可以维持软骨细胞的表型，而且可以调节宿主的炎症反应。将可注射的海藻酸钠（SA）/明胶（BG）水凝胶与可注射的热响应性SA/琼脂糖（AG）/槲皮素（Que）水凝胶混合以获得用于关节软骨再生的含有Que和BG两者的可注射水凝胶（Que-BG水凝胶）。Que-BG水凝胶具有适当的溶胀比，可以促进形成的组织与宿主组织之间的整合，并且它允许Que在原位缓慢释放以提高其生物利用度。Que-BG水凝胶可上调正常软骨细胞的SRY-盒9（SOX 9）、聚集蛋白聚糖（ACAN）和II型胶原α 1链（COL 2A 1）以维持正常软骨细胞表型。此外，它可以促进巨噬细胞M2极化，减轻炎症，并通过下调诱导型一氧化氮合酶（iNOS），基质金属蛋白酶-13（MMP-13）和基质金属蛋白酶-1（MMP-1）在退行性软骨细胞中的表达来抑制ECM降解。在将Que-BG水凝胶注射到大鼠软骨缺损模型中后，观察到形成的组织与正常组织相似，并且与周围组织高度整合。因此，可注射的Que-BG水凝胶改善了Que的生物利用度，维持了软骨细胞表型，抑制了ECM降解，并减少了炎症反应。
Articular cartilage plays an important role in human body. How to repair articular cartilage defects when they appear due to various factors has always been a major clinical challenge. Recently, studies have shown that slowing the degradation of cartilage extracellular matrix (ECM) and modulating the inflammatory response of the host thereby promoting cartilage tissue regeneration are important in the cartilage repair process. In this study, a drug-loaded injectable hydrogel was constructed for repairing articular cartilage. This hydrogel could not only maintain the phenotype of chondrocytes but also regulate the inflammatory response of the host. The injectable sodium alginate (SA)/bioglass (BG) hydrogel was mixed with the injectable thermal-responsive SA/agarose (AG)/quercetin (Que) hydrogel to obtain an injectable hydrogel containing both Que and BG (Que-BG hydrogel) for articular cartilage regeneration. The Que-BG hydrogel has a proper swelling ratio that can promote integration between the formed tissue and host tissue, and it allows Que to release slowlyin situto improve its bioavailability. The Que-BG hydrogel could upregulate SRY-box 9 (SOX9), aggrecan (ACAN), and collagen type II alpha 1 chain (COL2A1) of normal chondrocytes to maintain the normal chondrocyte phenotype. In addition, it could promote macrophage M2 polarization, reduce inflammation, and inhibit ECM degradation by downregulating the expression of inducible nitric oxide synthase (iNOS), matrix metalloproteinase-13 (MMP13), and matrix metalloproteinase-1 (MMP1) in degenerative chondrocytes. After injecting the Que-BG hydrogel into a rat cartilage defect model, the formed tissue was observed to be similar to the normal tissue and was highly integrated with the surrounding tissue. Therefore, the injectable Que-BG hydrogel improves Que bioavailability, maintains chondrocyte phenotype, inhibits ECM degradation, and reduces inflammatory response.