Biological Evaluation of Anti-Adhesion Device of Neurosurgery

神经外科防粘连装置的生物学评价

• 批准号: 7522306
• 负责人: CHARLES A FLOREK
• 金额: $ 3.73万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7522306
• 关键词: Address; Adhesions; Adhesives; Adsorption; Antibodies; Architecture; Biological; Biological Assay; Causations; Cells; Characteristics; Chemicals; Chemistry; Cicatrix; Clinical; Collagen; Cytoskeletal Modeling; Data; Device Designs; Devices; Dura Mater; Evaluation; Fibroblasts; Fluorescence Microscopy; Foreign-Body Giant Cells; Goals; Heating; Histology; Implant; In Vitro; Incidence; Inflammatory Response; Injury; Investigation; Laminectomy; Measures; Membrane; Meninges; Messenger RNA; Modeling; Monitor; Neuraxis; Operative Surgical Procedures; Penetration; Performance; Phenotype; Porosity; Prevention; Process; Production; Proteins; Rate; Rattus; Reverse Transcriptase Polymerase Chain Reaction; Score; Severities; Spinal Cord; Spinal cord injury; Surgical complication; System; Testing; Thick; Time; Tissues; Training; Trichrome stain; Tyrosine; United States; Work; capsule; career; cytokine; density; in vivo; insight; macrophage; neurosurgery; polycarbonate; prevent; research study; response; scaffold; spinal cord surgery

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.

描述（由申请人提供）：美国每年对中枢神经系统进行超过200万例外科手术，其中包括超过125，000例暴露脊髓的椎板切除术。硬脑膜和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。在钝性脊髓损伤中，由于脑膜的局部损伤，硬脑膜粘连的发生率特别高。我们假设一种合成的、可降解的、多孔的、细胞不可渗透的电纺屏障装置将有效地防止硬膜下和硬膜外粘连。将通过定制的化学成分和结构优化器械设计。酪氨酸衍生的聚碳酸酯化学可以通过共聚改性以改变蛋白质吸附和降解速率。静电纺丝过程可以产生细胞可渗透和细胞不可渗透的结构。将评价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的2 × 2基质的生物学性能。器械设计的主要标准是防止器械上产生连续疤痕，并将植入物周围的炎症反应降至最低。在体外，将通过荧光显微镜评价试验支架的成纤维细胞渗透和膜上的细胞骨架组织。作为炎症反应的体外预测因子，将通过RayBio大鼠细胞因子抗体阵列测定法测量巨噬细胞细胞因子分泌，并通过定量真实的时间逆转录酶聚合酶链反应测定法验证细胞因子mRNA的产生。将在大鼠非损伤椎板切除术模型中评价测试支架硬膜外粘附性能。马洛里三色染色将显示器械上是否形成连续的胶原瘢痕，并通过纤维囊厚度、巨噬细胞密度和是否存在异物巨细胞来评价炎症反应的严重程度。根据这些结果，将对支架化学或结构进行改进，或者将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，通过Keck中心的粘连评分系统进行评分。拟议的工作将提供跨学科的培训，以支持申请人的职业目标，同时解决脊髓手术的重大临床需求。