Tissue Engineered Total Disc Replacement in a Large Animal Model

标题：组织工程化全间盘置换在大动物模型中的应用 该项目的目标是开发一种组织工程化结构，包括工程化的 髓核纤维环治疗腰椎间盘退行性变 (IVD)。在具体目标1中，我们将在我们的初步小动物研究的基础上构建细胞- 其几何尺寸与人和山羊IVD相当的种子DAP。一本小说 将利用压缩-扭转生物反应器和模拟的体外盘状微环境 为了促进增长，我们还将建立终端板区域，以促进骨化一体化。在……里面 特定目的2，我们将研究生理负荷对体内DAP的影响 大动物(山羊)颈椎间盘置换术模型的成熟与融合。Pre- 成熟的DAPs结构将在单节段植入山羊颈椎。 颈椎髓核摘除术。无论使用或不使用集成的PCL泡沫塑料，均可植入支架 端板。植入后，一群动物将立即进行植入运动 颈椎前路钢板固定节段。另一批人将接受 无器械植入术。体内DAP的成熟度将通过MRI进行评估， 在我们之前的体内DAP工作中。将监测山羊颈椎和头部的运动 使用我们团队开发的定制大型动物运动跟踪设备。终端 分析将评估运动节段力学和DAP生化含量和ECM 植入后12周的分布。在具体目标3中，我们将调查重新动员 组织工程化运动节段和长期生存/节段分析 稳定性。目标2中生物力学性能最好的DAP将被植入 在椎间盘摘除后；在植入后12周，将取出内固定，恢复 无约束的运动。动物将继续自由放养活动12周， 定期获取宫颈运动和透视数据。植入后24周， 动物将被处死，植入DAP的运动节段将通过MRI进行评估 分析，生物力学测试，基质含量和分布的组织学分析，以及 生化分析。该项目的目标是开发组织工程化结构，并 评估它们在治疗退行性腰椎间盘疾病中的治疗潜力。这是意料之中的 拟议的研究将提供对退行性间盘疾病和 展示一种新的治疗方法的潜力。

Title: Tissue Engineered Total Disc Replacement in a Large Animal Model The objective of this project is to develop a tissue-engineered construct including an engineered nucleus pulposus and annulus fibrosus to treat degenerative changes of the intervertebral disc (IVD). In Specific Aim 1, we will build on our preliminary small animal studies to construct cell- seeded DAPS whose geometric dimensions are comparable to human and goat IVDs. A novel compression-torsion bioreactor and simulated ex vivo disc-like microenvironment will be utilized to promote growth; we will also establish an endplate region to promote boney integration. In Specific Aim 2, we will investigate the impact of physiological loading on DAPS in vivo maturation and integration in a large animal (goat) cervical spine disc replacement model. Pre- matured DAPS constructs will be implanted into the goat cervical spine following a single-level cervical discectomy. Constructs will be implanted either with or without an integrated PCL foam endplate. Immediately after implantation, a cohort of animals will have their implanted motion segment stabilized using an anterior cervical plate. An additional cohort will undergo implantation without instrumentation. In vivo DAPS maturation will be assessed via MRI, based on our prior in vivo DAPS work. Motion of the goat cervical spine and head will be monitored using a custom large animal motion-tracking device that our group has developed. Terminal assays will assess motion segment mechanics and DAPS biochemical content and ECM distribution at 12 weeks post-implantation. In Specific Aim 3, we will investigate remobilization of the tissue-engineered motion segment and analysis of longer-term viability/segmental stability. The DAPS construct with best biomechanical performance in Aim 2 will be implanted after discectomy; at 12 weeks post-implantation, instrumentation will be removed, restoring unconstrained motion. Animals will continue free-range activity for 12 additional weeks, with regular acquisition of cervical motion and fluoroscopy data. At 24 weeks post-implantation, animals will be sacrificed and DAPS-implanted motion segments will be assessed via MRI analysis, biomechanical testing, histological analysis of matrix content and distribution, and biochemical analysis. The goal of this project is to develop tissue-engineered constructs and to assess their therapeutic potential in the treatment of degenerative disc disease. It is anticipated that the proposed study will offer an increased understanding of degenerative disc disease and demonstrate the potential of a novel therapeutic treatment.