Biological Evaluation of Anti-Adhesion Device of Neurosurgery

描述（由申请人提供）：在美国，每年进行超过200万例中枢神经系统手术，包括超过125,000例暴露脊髓的椎板切除术。硬脑膜与周围组织之间的粘连性瘢痕，以及脊髓与硬脑膜的栓系是脊髓手术的严重并发症。在钝冲击脊髓损伤中，由于局部脑膜损伤，硬脑膜粘连的发生率特别高。我们假设一个合成的，可降解的，多孔的，细胞不渗透的静电纺屏障装置将有效地防止硬膜下和硬膜外粘连。设备设计将通过量身定制的化学成分和结构进行优化。酪氨酸衍生的聚碳酸酯可以通过共聚改性来改变蛋白质的吸附和降解速率。静电纺丝工艺可以产生细胞渗透性和细胞不渗透性的结构。将评估具有渗透性与非渗透性结构以及蛋白质吸附剂与非吸附剂化学性质的二乘二基质的生物性能。设备设计的主要标准是防止在设备上产生连续的疤痕，并将植入物周围的炎症反应降到最低。在体外，测试支架将通过荧光显微镜评估成纤维细胞对膜的渗透和细胞骨架组织。作为炎症反应的体外预测因子，巨噬细胞细胞因子的分泌将通过RayBio大鼠细胞因子抗体阵列测定，并通过定量实时逆转录酶聚合酶链反应测定来验证细胞因子mrna的产生。试验支架硬膜外粘连性能将在大鼠无损伤椎板切除术模型中进行评估。Mallory三色染色将显示是否在器械上形成连续的胶原瘢痕，并通过纤维囊厚度、巨噬细胞密度和异物巨细胞的存在来评估炎症反应的严重程度。有了这些结果，要么对支架的化学或结构进行改进，要么在大鼠脊髓损伤模型中测试支架的硬膜外和硬膜下抗粘连性能，并由Keck中心的粘连评分系统评分。建议的工作将提供跨学科的培训，以支持申请人的职业目标，同时解决脊髓外科的重要临床需求。

DESCRIPTION (provided by applicant): Over 2 million surgical operations are carried out on the central nervous system each year in the United States including over 125,000 laminectomies exposing the spinal cord. Adhesive scarring between the dura and surrounding tissues, as well as tethering of the spinal cord to the dura, are serious complications of spinal cord surgery. In blunt-impact spinal cord injury, the incidence of dural adhesion is especially high due to local injury to the meninges. We hypothesize that a synthetic, degradable, porous, cell-impermeable electrospun barrier device will effectively prevent subdural and epidural adhesions. Device design will be optimized through tailored chemical composition and architecture. Tyrosine- derived polycarbonate chemistry can be modified through copolymerization to vary protein adsorption and degradation rate. The electrospinning process can produce cell permeable and cell impermeable architectures. The biological performance of a two-by-two matrix of permeable versus non-permeable architecture and protein adsorbent versus non-adsorbent chemistry will be evaluated. The primary criteria for device design are to prevent the production of a continuous scar across the device and minimal inflammatory response around the implant. In vitro, test scaffolds will be evaluated for fibroblast penetration into and cytoskeletal organization on the membrane by fluorescence microscopy. As an in vitro predictor of inflammatory response, macrophage cytokine secretion will be measured by RayBio Rat Cytokine Antibody Array assays and verified by quantitative real time reverse transcriptase polymerase chain reaction assays for production of cytokine mRNAs. Test scaffold epidural adhesion performance will be evaluated in a rat non-injury laminectomy model. Mallory trichrome staining will reveal if a continuous collagen scar is formed across the device, and severity of inflammatory response will be evaluated by thickness of fibrous capsule, macrophage density, and presence of foreign body giant cells. With these results, either refinements will be made to the scaffold chemistry or architecture, or the scaffold will be tested for epidural and subdural anti-adhesion performance in a rat spinal cord injury model, scored by the Keck Center's adhesion scoring system. The proposed work will provide interdisciplinary training in support of the applicant's career goals while addressing a significant clinical need in spinal cord surgery.