Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai 200233, PR China.
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 708 Renmin Rd, Suzhou, Jiangsu 215006, PR China.
J Control Release. 2017 Oct 28;264:1-13. doi: 10.1016/j.jconrel.2017.08.011. Epub 2017 Aug 10.
Electrospun fibrous membranes provide suitable physical anti-adhesion barriers for reducing tissue anti-adhesion following surgery. However, often during the biodegradation process, these barriers trigger inflammation and cause a foreign body reaction with subsequent decrease in anti-adhesion efficacy. Here, a facile strategy comprising the incorporation of ibuprofen (IBU) into implantable membranes and its sustained release was proposed in order to improve anti-adhesion effects and neurological outcomes, namely to prevent failed back surgery syndrome (FBSS). The combination of free IBU and a newly synthetized polymeric prodrug of IBU, namely poly(hydroxyethyl methacrylate) with ester-linked IBU, was successfully used in order to reduce initial burst drug release and provide sustained drug release from fibrous membranes throughout several weeks. Such release profile was shown useful in preventing both acute and chronic inflammation in rats following laminectomy and membrane implantation. Moreover, histological analysis provided evidence of an excellent anti-adhesion effect, while associated neurological deficits were effectively reduced. Furthermore, the assessment of macrophage density, neovascularization, and related gene expression at the lesion site revealed that a sustained anti-inflammatory effect was achieved with the IBU-loaded proposed fibrous membranes. Results suggested that the COX2 pathway plays an important role in the development epidural fibrosis and arachnoiditis. Overall, this study provided evidence that precisely engineered IBU-loaded electrospun fibrous membranes may be useful in preventing FBSS and able to potentially impact the outcome of patients undergoing spine surgery.
静电纺丝纤维膜为减少手术后组织粘连提供了合适的物理防粘连屏障。然而,在生物降解过程中,这些屏障常常引发炎症,并导致异物反应,随后降低防粘连效果。在这里,提出了一种简便的策略,即将布洛芬(IBU)掺入可植入膜中并进行持续释放,以提高防粘连效果和神经学结果,即预防失败性腰椎后手术综合征(FBSS)。游离 IBU 与新合成的 IBU 聚合物前药聚(羟乙基甲基丙烯酸酯)与酯键连接的 IBU 的组合成功地用于减少初始突释药物释放,并使纤维膜在数周内持续释放药物。这种释放曲线被证明可有效预防椎管切开术和膜植入术后大鼠的急性和慢性炎症。此外,组织学分析提供了良好的防粘连效果的证据,同时有效减少了相关的神经功能缺损。此外,对病变部位的巨噬细胞密度、新生血管形成和相关基因表达的评估表明,载有 IBU 的提出的纤维膜具有持续的抗炎作用。结果表明,COX2 途径在硬膜外纤维化和蛛网膜炎的发展中起着重要作用。总的来说,这项研究提供了证据,表明精确设计的载有 IBU 的静电纺丝纤维膜可能有助于预防 FBSS,并有可能影响接受脊柱手术的患者的治疗效果。