Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China; College of Chemical Engineering, Fuzhou University, 2 Xueyuan Road, Fuzhou 350108, PR China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China.
J Control Release. 2021 Jul 10;335:359-368. doi: 10.1016/j.jconrel.2021.04.017. Epub 2021 Apr 22.
Peritendinous adhesion, secondary to the repair surgery of tendon rupture or injury, is one of the most common causes of reoperation, owing to the proliferation of fibrous tissue and excessive collagen synthesis caused by the residing inflammatory cells. In this study, a smart oxidative stress-responsive electrospun polyester membrane (EPM) was fabricated as both physical barrier and reservoir of curcumin/celecoxib (CUR/CEL) to prevent peritendinous adhesion. The multicomponent EPM was designed to release the encapsulated drugs in response to oxidative stress of the local microenvironment induced by inflammation. Specifically, sulfides in the EPM were able to react with reactive oxygen species (ROS) and become hydrophilic sulfoxide or sulfone to accelerate the release rate of drugs and regulate oxidative stress level in the inflammatory site intelligently. The oxidation-sensitive multicomponent EPM loaded with CUR and CEL was tested for anti-adhesion capacity in vitro and in vivo. An excellent ROS-sensitive degradation behavior and good cytocompatibility with cell viability of above 85% were presented with the fabricated EPM. The CUR- or CEL-loaded EPM possessed a better anti-adhesion ability compared with EPM without the drugs. Nevertheless, they were inferior to the EPM simultaneously loaded with both drugs, where the adhesion rate and fibrous adhesion number in the EPM+CUR/CEL group were close to extremely low values of about zero, demonstrating that CUR and CEL could synergistically prevent peritendinous adhesion. More interestingly, the multicomponent EPM was able to react with the local oxidative stress, leading to a smart and sustained behavior of releasing approximately 80% of the drug within 20 days. Overall, the smart multicomponent EPM offers a promising barrier strategy to prevent peritendinous adhesion.
腱周粘连是肌腱断裂或损伤修复术后最常见的再手术原因之一,这是由于驻留的炎症细胞引起的纤维组织增生和胶原过度合成。在这项研究中,制备了一种智能氧化应激响应型静电纺聚酯膜(EPM),作为物理屏障和姜黄素/塞来昔布(CUR/CEL)的储库,以防止腱周粘连。多组分 EPM 的设计是为了响应炎症引起的局部微环境中的氧化应激,释放包裹的药物。具体而言,EPM 中的硫醚能够与活性氧(ROS)反应,变成亲水性亚砜或砜,从而加速药物的释放速度,并智能调节炎症部位的氧化应激水平。对负载 CUR 和 CEL 的氧化敏感型多组分 EPM 进行了体外和体内抗粘连能力测试。所制备的 EPM 具有出色的 ROS 敏感降解行为和良好的细胞相容性,细胞活力超过 85%。负载 CUR 或 CEL 的 EPM 与不含药物的 EPM 相比具有更好的抗粘连能力。然而,它们不如同时负载两种药物的 EPM 好,其中 EPM+CUR/CEL 组的粘连率和纤维粘连数接近接近零的极低值,表明 CUR 和 CEL 可以协同预防腱周粘连。更有趣的是,多组分 EPM 能够与局部氧化应激反应,导致在 20 天内智能且持续地释放大约 80%的药物。总体而言,智能多组分 EPM 为预防腱周粘连提供了一种有前途的屏障策略。