1. Uni-directional release of ibuprofen from an asymmetric fibrous membrane enables effective peritendinous anti-adhesion.
- Author
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Deng, Jixia, Yao, Zhixiao, Wang, Shikun, Zhang, Xinyu, Zhan, Lei, Wang, Tongyu, Yu, Wenhua, Zeng, Jiamei, Wu, Jinglei, Fu, Shaoju, Wu, Shihao, Ouyang, Yuanming, and Huang, Chen
- Subjects
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IBUPROFEN , *TISSUE adhesions , *PHARMACOKINETICS , *ANTI-inflammatory agents , *GUIDED tissue regeneration ,TENDON injury healing - Abstract
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 in situ 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. In vivo 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. [Display omitted] • Uni-directional and sustained release of ibuprofen (IBU) was achieved in an asymmetric fibrous scaffold. • IBU release was prolonged by the porous and bundle structure of poly-l-lactic acid (PLLA) fibers. • Uni-directional drug release (release rate = 81.1% and 0.3% at two sides) was achieved to selectively inhibit cell growth. • Anti-adhesion was realized at the high IBU concentration side without affecting tendon healing at the other side. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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