Yu Weihan, Zhu Yanlun, Li Haiyan, He Yaohua
Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China.
Department of Orthopedics, Shanghai General Hospital, Shanghai 200080, China.
ACS Appl Bio Mater. 2020 Feb 17;3(2):761-771. doi: 10.1021/acsabm.9b00673. Epub 2020 Jan 13.
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 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.
关节软骨在人体中起着重要作用。当由于各种因素出现关节软骨缺损时，如何修复这些缺损一直是临床上面临的重大挑战。最近的研究表明，减缓软骨细胞外基质（ECM）的降解并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至关重要。在本研究中，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，以获得一种同时含有Que和BG的可注射水凝胶（Que-BG水凝胶）用于关节软骨再生。Que-BG水凝胶具有合适的溶胀率，可促进形成的组织与宿主组织之间的整合，并使Que缓慢释放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盒9（SOX9）、聚集蛋白聚糖（ACAN）和II型胶原α1链（COL2A1），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，并通过下调退变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）的表达来抑制ECM降解。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，并与周围组织高度整合。因此，可注射的Que-BG水凝胶提高了Que的生物利用度，维持了软骨细胞表型，抑制了ECM降解，并减轻了炎症反应。
