Injectable Quercetin-Loaded Hydrogel with Cartilage-Protection and Immunomodulatory Properties for Articular Cartilage Repair,ACS Applied Bio Materials

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Injectable Quercetin-Loaded Hydrogel with Cartilage-Protection and Immunomodulatory Properties for Articular Cartilage Repair
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-01-13 , DOI: 10.1021/acsabm.9b00673
Weihan Yu _{1,

2} , Yanlun Zhu _{3,

4} , Haiyan Li _{1,

3} , Yaohua He _{1,

5}

Affiliation

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 slowly in situ to 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.

中文翻译：

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

关节软骨在人体中起着重要作用。如何修复因各种因素而出现的关节软骨缺损一直是临床的一大挑战。最近的研究表明，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很重要。在这项研究中，构建了一种用于修复关节软骨的载药可注射水凝胶。这种水凝胶不仅可以维持软骨细胞的表型，还可以调节宿主的炎症反应。将可注射的海藻酸钠 (SA)/生物玻璃 (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，以获得含有 Que 和 BG (Que-BG 水凝胶) 的可注射水凝胶。关节软骨再生。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融合，并让 Que 缓慢释放原位以提高其生物利用度。Que-BG 水凝胶可以上调正常软骨细胞的 SRY-box 9 (SOX9)、聚集蛋白聚糖 (ACAN) 和 II 型胶原蛋白 α1 链 (COL2A1) 以维持正常的软骨细胞表型。此外，它还可以通过下调退行性软骨细胞中诱导型一氧化氮合酶 (iNOS)、基质金属蛋白酶 13 (MMP13) 和基质金属蛋白酶 1 (MMP1) 的表达来促进巨噬细胞 M2 极化、减轻炎症和抑制 ECM 降解。将 Que-BG 水凝胶注入大鼠软骨缺损模型后，观察到形成的组织与正常组织相似，并与周围组织高度融合。因此，可注射的 Que-BG 水凝胶提高 Que 生物利用度，维持软骨细胞表型，抑制 ECM 降解，

更新日期：2020-01-13

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