Shi Rui, Huang Yuelong, Zhang Jingshuang, Wu Chengai, Gong Min, Tian Wei, Zhang Liqun
Beijing Laboratory of Biomedical Materials, Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing, China.
Department of Spine Surgery, Peking University Fourth School of Clinical Medicine, Beijing, China.
J Biomed Mater Res B Appl Biomater. 2020 Feb;108(2):353-366. doi: 10.1002/jbm.b.34394. Epub 2019 Apr 24.
Epidural adhesion between the spinal dura and the surrounding fibrous tissue often occurs post-laminectomy, resulting in clinical symptoms such as nerve compression and severe pain. In this study, we report a drug-loaded double-layered electrospun nanofiber membrane to prevent the occurrence of epidural adhesion. The nanofibers in both layers are made of a mixture of polycaprolactone (PCL) and chitosan (CS) but at different weight ratios. The bottom layer contacting to the spinal dura is loaded with meloxicam (MX) to prevent inflammation. The top layer that contacts to the fibrous tissue is doped with mitomycin-C (MMC) to inhibit the synthesis of DNA and collagen. The two types of drugs are released from the double-layered membrane within about 12 days. Meanwhile, the membrane can inhibit fibroblasts proliferation in vitro while show no cytotoxicity. In a rabbit laminectomy model, the double-layered membrane can effectively prevent the epidural adhesion formation based on the adhesion scores, histological and biochemical evaluations. The combination release of MX and MMC can signally reduce the inflammation reaction and collagen I/III expression relative to the case with the membranes loaded with only either one type of the drugs. This approach offers new progresses in constructing dual drug delivery system and provides innovative barrier strategy in inhibiting epidural adhesion post-laminectomy.
椎板切除术后，脊髓硬脊膜与周围纤维组织之间常发生硬膜外粘连，导致神经受压和剧痛等临床症状。在本研究中，我们报道了一种载药双层电纺纳米纤维膜，以防止硬膜外粘连的发生。两层纳米纤维均由聚己内酯（PCL）和壳聚糖（CS）的混合物制成，但重量比不同。与脊髓硬脊膜接触的底层负载美洛昔康（MX）以预防炎症。与纤维组织接触的顶层掺杂丝裂霉素-C（MMC）以抑制DNA和胶原蛋白的合成。两种药物在约12天内从双层膜中释放。同时，该膜在体外可抑制成纤维细胞增殖，且无细胞毒性。在兔椎板切除模型中，基于粘连评分、组织学和生化评估，双层膜可有效防止硬膜外粘连形成。相对于仅负载一种药物的膜，MX和MMC的联合释放可显著减轻炎症反应和I/III型胶原蛋白表达。该方法在构建双药递送系统方面取得了新进展，并为抑制椎板切除术后硬膜外粘连提供了创新的屏障策略。
