Orthopedic Institute, Soochow University, 708 Renmin Rd, Suzhou, Jiangsu 215006, People's Republic of China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, 1954 Huashan Rd, Shanghai 200030, People's Republic of China.
Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Rd, Shanghai 200233, People's Republic of China.
Acta Biomater. 2014 Jul;10(7):3018-28. doi: 10.1016/j.actbio.2014.03.023. Epub 2014 Apr 3.
Vasospasm is a common post-operative complication after vascular anastomosis. Currently, the main treatment is a local injection of antispasmodic drugs. However, this method has a high rate of relapse and is subject to a large degree of individual variation, and repeated injections cause additional pain for patients. In this study, we developed highly flexible and rapidly degradable papaverine-loaded electrospun fibrous membranes to be wrapped around vascular suturing to prevent vasospasm. Poly-l-lactic acid/polyethylene glycol (PLLA/PEG) electrospun fibers containing papaverine maintained a high degree of flexibility and could withstand any folding, and are therefore suitable for wrapping vascular suturing. A rapid release of papaverine, between 2 and 7 days, was achieved by adjusting the proportions of PEG and PLLA. PLLA electrospun fibers containing 40% PEG (PLLA-40%) could control drug release and polymer degradation most effectively during the first 2 weeks post-operation. Testing using an in vivo rabbit model showed that PLLA-40% fibrous membranes produced significant antispasmodic effect without observable inflammation or hyperplasia, and the fibrous membranes were ideally biodegradable, with no impact on regional blood flow, pressure, vessel diameter or surrounding tissue hyperplasia. Therefore, papaverine-loaded electrospun fibrous membranes show the potential to greatly reduce post-operative vasospasm and maintain regular vascular morphology during antispasmodic therapy.
血管痉挛是血管吻合术后的一种常见并发症。目前，主要的治疗方法是局部注射解痉药物。然而，这种方法的复发率很高，且受个体差异影响较大，并且反复注射会给患者带来额外的疼痛。在这项研究中，我们开发了高度灵活和快速降解的罂粟碱负载电纺纤维膜，用于包裹血管缝合处，以防止血管痉挛。含有罂粟碱的聚 L-乳酸/聚乙二醇（PLLA/PEG）电纺纤维保持高度的柔韧性，可以承受任何折叠，因此适合包裹血管缝合处。通过调整 PEG 和 PLLA 的比例，可以实现罂粟碱的快速释放，在 2 到 7 天之间。含有 40%PEG 的 PLLA 电纺纤维（PLLA-40%）可以在术后前 2 周内最有效地控制药物释放和聚合物降解。使用体内兔模型进行的测试表明，PLLA-40%纤维膜产生了显著的解痉作用，没有观察到炎症或增生，并且纤维膜具有理想的生物降解性，对局部血流、压力、血管直径或周围组织增生没有影响。因此，罂粟碱负载电纺纤维膜有望大大减少术后血管痉挛，并在解痉治疗期间保持血管形态的规律性。
