■肌腱损伤后粘连的形成是肌腱修复的主要障碍,目前临床上尚无有效的防粘连方法。氧化应激,炎症,肌腱损伤可发生纤维化,这些因素可导致肌腱粘连。抗氧化碳点和熊果酸(UA)都具有抗氧化和抗炎特性。在这个实验中,我们首次使用红色荧光碳点和UA共包裹的脂质体复合透明质酸甲基丙烯酰水凝胶创建了RCDs/UA@Lipo-HAMA。我们发现RCD/UA@Lipo-HAMA可以更好地减轻肌腱损伤中的粘连形成并增强肌腱愈合。
■制备并表征RCD/UA@Lipo-HAMA。进行了细胞氧化应激和纤维化的体外实验。活性氧(ROS),和I型胶原蛋白(COLI)的免疫荧光染色,胶原蛋白III型(COLIII),和α-平滑肌肌动蛋白(α-SMA)用于评估抗氧化和抗纤维化能力。建立跟腱损伤修复(ATI)和趾深屈肌腱损伤修复(FDPI)的体内模型。对大鼠的主要器官和血液生化指标进行检测,以确定RCD/UA@Lipo-HAMA的毒性。生物力学测试,运动功能分析,免疫荧光,并进行免疫组织化学染色以评估肌腱损伤后的肌腱粘连和修复。
■体外,RCD/UA@Lipo组清除了过量的ROS,稳定线粒体膜电位(ΔkW),并降低COLI的表达,COLIII,和α-SMA。在体内,评估结果表明,RCDs/UA@Lipo-HAMA组改善了胶原排列和生物力学特性,减少肌腱粘连,促进肌腱损伤后的运动功能。此外,RCDs/UA@Lipo-HAMA组核因子红细胞相关因子2(Nrf2)和血红素加氧酶1(HO-1)的表达增加;分化簇68(CD68)诱导型一氧化氮合酶(iNOS),COLIII,α-SMA,Vimentin,基质金属肽酶2(MMP2)降低。
■在这项研究中,RCD/UA@Lipo-HAMA通过减轻氧化应激减轻肌腱粘连形成并增强肌腱愈合,炎症,和纤维化。本研究为肌腱损伤的临床治疗提供了一种新的治疗方法。
UNASSIGNED: The formation of adhesion after tendon injury represents a major obstacle to tendon repair, and currently there is no effective anti-adhesion method in clinical practice. Oxidative stress, inflammation, and fibrosis can occur in tendon injury and these factors can lead to tendon adhesion. Antioxidant carbon dots and ursolic acid (UA) both possess antioxidant and anti-inflammatory properties. In this experiment, we have for the first time created RCDs/UA@Lipo-HAMA using red fluorescent carbon dots and UA co-encapsulated liposomes composite hyaluronic acid methacryloyl hydrogel. We found that RCDs/UA@Lipo-HAMA could better attenuate adhesion formation and enhance tendon healing in tendon injury.
UNASSIGNED: RCDs/UA@Lipo-HAMA were prepared and characterized. In vitro experiments on cellular oxidative stress and fibrosis were performed. Reactive oxygen species (ROS), and immunofluorescent staining of collagens type I (COL I), collagens type III (COL III), and α-smooth muscle actin (α-SMA) were used to evaluate anti-oxidative and anti-fibrotic abilities. In vivo models of Achilles tendon injury repair (ATI) and flexor digitorum profundus tendon injury repair (FDPI) were established. The major organs and blood biochemical indicators of rats were tested to determine the toxicity of RCDs/UA@Lipo-HAMA. Biomechanical testing, motor function analysis, immunofluorescence, and immunohistochemical staining were performed to assess the tendon adhesion and repair after tendon injury.
UNASSIGNED: In vitro, the RCDs/UA@Lipo group scavenged excessive ROS, stabilized the mitochondrial membrane potential (ΔΨm), and reduced the expression of COL I, COL III, and α-SMA. In vivo, assessment results showed that the RCDs/UA@Lipo-HAMA group improved collagen arrangement and biomechanical properties, reduced tendon adhesion, and promoted motor function after tendon injury. Additionally, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the RCDs/UA@Lipo-HAMA group increased; the levels of cluster of differentiation 68 (CD68), inducible Nitric Oxide Synthase (iNOS), COL III, α-SMA, Vimentin, and matrix metallopeptidase 2 (MMP2) decreased.
UNASSIGNED: In this study, the RCDs/UA@Lipo-HAMA alleviated tendon adhesion formation and enhanced tendon healing by attenuating oxidative stress, inflammation, and fibrosis. This study provided a novel therapeutic approach for the clinical treatment of tendon injury.