Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai, 200233, P. R. China.
Section of Spine Surgery, Department of Orthopaedics, Changzheng Hospital, Naval Medical University, Shanghai, 200003, P. R. China.
Adv Healthc Mater. 2023 Jun;12(15):e2203078. doi: 10.1002/adhm.202203078. Epub 2023 Mar 11.
The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFβ) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFβ/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.
外伤性肌腱周围粘连（PA）的预防和治疗一直是骨科医生面临的一大难题。目前的治疗方法包括切除术、非甾体抗炎药（NSAIDs）的使用和可植入膜，但这些方法通常针对单一的疾病发病过程，导致治疗效果不佳。在这里，我们生成了一种聚乳酸（PLA）-双香豆素缀合物-静电纺纳米纤维膜（PCD），它可以实现药物释放的空间准确性和时间持续性。进一步的研究表明，PCD 具有比传统载药 ENM 更高和更持续的药物释放特性。通过提供物理屏障和持续释放双香豆素，PCD 的植入显著降低了 25%的组织粘连，降低了成纤维细胞的活性，并抑制了关键的纤维化细胞因子转化生长因子β（TGFβ）的产生达 30%，同时提高了肌腱的生物力学性能达 14.69%。在机制上，PCD 能够强烈抑制连接蛋白 43（Cx43），从而下调成纤维细胞的 TGFβ/Smad3 信号通路。因此，这种方法利用了双香豆素的抗粘连作用和接枝共聚物 ENM 的药物释放特性，为患有 PA 的患者提供了一种有前途的治疗策略。
