Department of Orthopaedic Surgery, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, China.
Department of Surgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Drug Deliv. 2021 Dec;28(1):1290-1300. doi: 10.1080/10717544.2021.1938752.
In the human body, joint cartilage is of great importance. It has long been a big therapeutic problem to fix joint cartilage lesions as it appears due to different conditions. Recent stories have shown that the cartilage replacement process must delay the extracellular (ECM) cartilage deterioration and modulate the host's inflammation response. For the reconstruction of the articular cartilage, drug-loaded injectable hydrogels were developed. This hydrogel could retain the chondrocyte phenotype, but the host's inflammatory reaction could also be controlled. The bioglass (BG)/sodium alginate (SA) injectable hydrogels was combined with agarose (AG)/Naringin hydrogel in injectable thermal response for articular cartilage regeneration with a non-chargeable hydrogel that contains both Naringin and BG (Naringin-BG hydrogels). The Naringin-BG hydrogel has an adequate swelling ratio that encourages the fusion of tissue formed with host tissue and enables the gradual release of Naringin bioavailabilities enhanced . The Naringin-BG hydrogel can upgrade the typical chondrocyte phenotype by upregulating aggrecan, SRY-box 9, and collagen type II alpha one chain. It may also stimulate the polarization of M2 macrophage, lower inflammations, and prevent ECM degradations through the decrease of the expressions of the indictable metalloproteinase-13 matrix, nitric oxide synthase, and metalloproteinase-1 matrix. The formed tissues were identical to normal tissues and firmly incorporated with the surrounding tissue after administering the Naringin-BG hydrogels into the rat model articular cartilage defects. Then the injectable Naringin-BG hydrogel increases the bioavailable content of Naringin and retains the chondrocyte phenotype.
在人体中,关节软骨非常重要。由于不同的情况导致关节软骨损伤,修复关节软骨一直是一个很大的治疗难题。最近的研究表明,软骨替代过程必须延缓细胞外基质(ECM)软骨的恶化,并调节宿主的炎症反应。为了重建关节软骨,开发了载药可注射水凝胶。这种水凝胶可以保留软骨细胞表型,但也可以控制宿主的炎症反应。将生物玻璃(BG)/海藻酸钠(SA)可注射水凝胶与琼脂糖(AG)/柚皮苷水凝胶相结合,用于关节软骨再生的可注射热响应,形成一种含有柚皮苷和 BG(柚皮苷-BG 水凝胶)的非荷电水凝胶。柚皮苷-BG 水凝胶具有足够的溶胀比,可促进与宿主组织融合的组织形成,并能逐渐释放生物利用度增强的柚皮苷。柚皮苷-BG 水凝胶通过上调聚集蛋白聚糖、性别决定区 Y-box 9 和胶原 II 型α链,可提升典型的软骨细胞表型。它还可以通过降低指示性基质金属蛋白酶-13 基质、一氧化氮合酶和基质金属蛋白酶-1 基质的表达,刺激 M2 巨噬细胞的极化,降低炎症反应,防止 ECM 降解。将柚皮苷-BG 水凝胶注入大鼠关节软骨缺损模型后,形成的组织与正常组织相似,并与周围组织牢固融合。然后,可注射的柚皮苷-BG 水凝胶增加了柚皮苷的生物利用度,并保留了软骨细胞表型。