氟化共价有机框架水凝胶重编程Piezo1/YAP机械转导以实现对腱周粘连的持续预防
Fluorinated covalent organic framework hydrogel reprograms Piezo1/YAP mechanotransduction for sustained prevention of peritendinous adhesion.
摘要(中文译文)
术后腱周粘连源于持续的成纤维细胞活性、胶原过度产生以及肌腱修复过程中机械信号传导失调；然而，目前很少有治疗手段能够在愈合的增殖期实现持久的分子干预。在此，我们开发了一种氟化共价有机框架水凝胶Thi@FCOF@Gel，可实现盐酸硫利达嗪的时间控制释放，从而持续预防腱周粘连。通过表型药物筛选，盐酸硫利达嗪（Thi）被鉴定为一种此前未被认识到的抗粘连药物，能够选择性抑制成纤维细胞增殖和肌成纤维细胞活化，同时对腱源性干细胞的抑制作用有限。为使药物暴露与粘连形成同步，将硫利达嗪封装于氟化COF中，并整合入透明质酸/季铵化壳聚糖水凝胶，形成一种可注射、自愈合且机械增强的局部储库，具有延长释放行为。在机制上，含硫利达嗪的水凝胶通过下调Piezo1、增加YAP磷酸化并抑制α-SMA和III型胶原表达，减弱细胞外基质相关机械信号传导。在大鼠跟腱修复模型中，Thi@FCOF@Gel显著减少了纤维性桥接、胶原沉积和粘连评分，同时改善步态恢复，且不损害肌腱生物力学完整性或全身安全性。本研究不仅揭示了Thi的新抗粘连应用，还提供了一种基于COF的水凝胶策略，用于术后粘连管理中的精准局部药物递送。
Abstract
Postoperative peritendinous adhesion arises from sustained fibroblast activity, collagen overproduction, and dysregulated mechanical signaling during tendon repair; however, few current treatments can deliver a prolonged molecular intervention across the proliferative stage of healing. Here, we developed a fluorinated covalent organic framework hydrogel, Thi@FCOF@Gel, that enables temporally controlled delivery of thioridazine hydrochloride for sustained prevention of peritendinous adhesion. Through phenotypic drug screening, thioridazine hydrochloride (Thi) is identified as a previously unrecognized anti-adhesion agent capable of selectively suppressing fibroblast proliferation and myofibroblast activation while exerting limited inhibitory effects on tendon-derived stem cells. To synchronize drug exposure with adhesion formation, thioridazine was encapsulated into a fluorinated COF and incorporated into a hyaluronic acid/quaternized chitosan hydrogel, yielding an injectable, self-healing and mechanically reinforced local depot with prolonged release behavior. Mechanistically, thioridazine-containing hydrogels attenuated extracellular matrix-associated mechanosignaling by downregulating Piezo1, increasing YAP phosphorylation and suppressing α-SMA and collagen III expression. In a rat Achilles tendon repair model, Thi@FCOF@Gel markedly reduced fibrotic bridging, collagen deposition and adhesion scores, while improving gait recovery without compromising tendon biomechanical integrity or systemic safety. This study not only reveals a new anti-adhesion application of Thi, but also provides a COF-enabled hydrogel strategy for precise local drug delivery in postoperative adhesion management.
如何引用
AMA
Baoyiyu Xu, Jinlan Luo, Sa Pang, Chengchao Tu, Jiacheng Hu, Junjie Zhao, et al. Fluorinated covalent organic framework hydrogel reprograms Piezo1/YAP mechanotransduction for sustained prevention of peritendinous adhesion.. Bioactive materials. 2027; doi:10.1016/j.bioactmat.2026.07.039.
APA
Baoyiyu Xu, Jinlan Luo, Sa Pang, Chengchao Tu, Jiacheng Hu, Junjie Zhao, et al (2027). Fluorinated covalent organic framework hydrogel reprograms Piezo1/YAP mechanotransduction for sustained prevention of peritendinous adhesion.. Bioactive materials. https://doi.org/10.1016/j.bioactmat.2026.07.039
GB/T 7714
Baoyiyu Xu, Jinlan Luo, Sa Pang, Chengchao Tu, Jiacheng Hu, Junjie Zhao, et al. Fluorinated covalent organic framework hydrogel reprograms Piezo1/YAP mechanotransduction for sustained prevention of peritendinous adhesion.[J]. Bioactive materials, 2027 doi:10.1016/j.bioactmat.2026.07.039.
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