关键词: Amniotic membrane Anti-inflammation Electrospun polyester membrane Inflammatory microenvironment Tendon adhesion

来  源:   DOI:10.1016/j.heliyon.2023.e23214   PDF(Pubmed)

Abstract:
Tendon adhesion is a common complication after tendon surgery. The inflammatory phase of tendon healing is characterized by the release of a large number of inflammatory factors, whose mediated excessive inflammatory response is an important cause of tendon adhesion formation. Nonsteroidal anti-inflammatory drugs(NSAIDs) were used to prevent tendon adhesions by reducing the inflammatory response. However, recent studies have shown that the NSAIDs partially impairs tendon healing. Therefore, optimizing the anti-adhesive membrane loaded with NSAIDs to mitigate the effects on tendon healing requires further in-depth study. Amniotic membranes(AM) are natural polymeric semi-permeable membranes from living organisms that are rich in matrix, growth factors, and other active ingredients. In this study, we used electrostatic spinning technology to construct multifunctional nanofiber membranes of the PCL membrane loaded with celecoxib and AM. In vitro cellular assays revealed that celecoxib-loaded PCL membranes significantly inhibited the adhesion and proliferation of fibroblasts with increasing concentrations of celecoxib. In a rabbit tendon repair model, biomechanical tests further confirmed that the PCL membrane loaded with celecoxib had better anti-adhesion effects. Further experimental studies revealed that the PCL/AM membrane improved the inflammatory microenvironment by downregulating the expression of pro-inflammatory factors such as COX-2, IL-1β, and TNF-α proteins; and inhibiting the synthesis of COL I and COL Ⅲ. The PCL/AM membrane can continuously release celecoxib to reduce the inflammatory response and deliver growth factors to the damaged area to build a suitable microenvironment for tendon repair, which provides a new direction to improve the repair efficiency of tendon.
摘要:
肌腱粘连是肌腱手术后常见的并发症。肌腱愈合的炎症阶段的特点是大量炎症因子的释放,其介导的过度炎症反响是肌腱粘连构成的重要缘由。非甾体抗炎药(NSAIDs)用于通过减少炎症反应来预防肌腱粘连。然而,最近的研究表明,NSAIDs部分损害肌腱愈合。因此,优化加载NSAIDs的抗粘连膜以减轻对肌腱愈合的影响需要进一步深入研究.羊膜(AM)是来自富含基质的生物体的天然聚合物半透膜,生长因子,和其他活性成分。在这项研究中,我们采用静电纺丝技术构建了负载塞来昔布和AM的PCL膜的多功能纳米纤维膜。体外细胞测定显示,随着塞来昔布浓度的增加,负载塞来昔布的PCL膜显着抑制成纤维细胞的粘附和增殖。在兔肌腱修复模型中,生物力学测试进一步证实,负载塞来昔布的PCL膜具有更好的抗粘连效果。进一步的实验研究表明,PCL/AM膜通过下调COX-2、IL-1β等促炎因子的表达,改善炎症微环境,和TNF-α蛋白;并抑制COLⅠ和COLⅢ的合成。PCL/AM膜可持续释放塞来昔布以减轻炎症反应,并将生长因子传递到受损区域,为肌腱修复建立合适的微环境,为提高肌腱的修复效率提供了新的方向。
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