Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.

中文翻译：

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从不对称纤维膜中单向释放布洛芬可有效实现腱周抗粘连


载药多孔膜被认为是有效的物理化学屏障，可在肌腱愈合中分离术后易粘连的组织。然而，细胞活力和随后的组织再生可能会受到抗炎药物的无限制释放和局部浓度过高的严重干扰。在此，我们报告了一种具有持续和单向药物输送特性的双层膜，可防止腱周粘连而不妨碍愈合结果。采用涡流辅助静电纺丝系统与布洛芬（IBU）水包乳液相结合，制备了负载 IBU 的聚乳酸（PLLA）纤维束膜（PFB-IBU）作为防粘层。由此产生的 PLLA 纤维的高度多孔结构、亲油和疏水性质使得 IBU 能够在膜厚度上以浓度梯度负载。对齐的胶原纳米纤维进一步沉积在膜的低IBU浓度侧，用于调节细胞生长并实现IBU的单向释放。药物释放动力学表明，14 d时，高浓度侧IBU释放量达到79.32%，而胶原侧仅为0.35%。因此，成功抑制了高浓度一侧的成纤维细胞增殖，且不影响另一侧肌腱干细胞的定向生长。 对大鼠跟腱粘连模型的评估证实了我们的双层膜成功的腱周抗粘连，巨噬细胞的募集、炎症因子的分泌以及病理粘连标记物（如α-SMA和COL-III）的沉积均受到抑制，大大改善了腱周纤维化，恢复了肌腱的运动功能。