Mechano-active annular repair device for treating disc herniation

治疗椎间盘突出症的机械主动环形修复装置

• 批准号: 10631856
• 负责人: Harvey E. Smith
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10631856
• 关键词: Activities of Daily Living; Address; Adult; Animals; Anterolateral; Anti-Inflammatory Agents; Biochemistry; Biocompatible Materials; Biological Assay; Biological Products; Biomechanics; Bioreactors; Cadaver; Cells; Cervical spine; Clinical; Clinical Trials; Confocal Microscopy; Custom; Data; Defect; Devices; Drug Delivery Systems; Environment; Exposure to; Freedom; Goals; Goat; Health; Height; Histologic; Histology; Implant; In Vitro; Incidence; Individual; Infiltration; Inflammation; Injury; Intervention; Intervertebral disc structure; Magnetic Resonance Imaging; Maps; Mechanics; Methods; Microcapsules drug delivery system; Military Personnel; Modeling; Motion; Natural regeneration; Operative Surgical Procedures; Outcome; Pain in lower limb; Patients; Physiological; Pilot Projects; Population; Procedures; Property; RNA Interference; Randomized; Recurrence; Risk; Second Look Surgery; Services; Site; Slipped Disk; Spinal; Spine surgery; Strenuous Exercise; Structure; Surgical sutures; Symptoms; System; Technology; Thick; Thinness; Time; Tissue Engineering; Tissues; Torsion; Vertebral column; Veterans; Weight-Bearing state; Work; active duty; biomechanical test; clinical practice; comparison control; delivery vehicle; design; experience; fabrication; implantation; improved; in vivo; in vivo Model; injured; joint mobilization; mechanical load; mechanical properties; novel; preservation; professional atmosphere; recruit; release factor; repair strategy; repaired; response; scaffold; subcutaneous; success; tissue repair; translation to humans; treatment group; wound environment

Symptomatic lumbar disc herniations occur in 0.5 to 2 % of the adult population annually, with a higher incidence in individual exposed to strenuous activities in their work environments, including active duty military personnel. A lumbar microdiscectomy is very effective at addressing the extruded disc fragment and alleviating radicular leg pain. However, there is currently no established method to repair the annular defect. The injured annulus fibrosus has altered mechanical properties, and it is well recognized that larger annular defects are associated with an increased risk of recurrent disc herniation at that interspace. With this loss of AF function, the motion segment is also at risk for further degeneration, and loss of disc space height and further degeneration is a common sequelae of lumbar disc herniations. There are currently no effective clinical interventions targeted at repairing the annulus fibrous in a manner that recapitulates the native disc. The objective of this project is to develop a novel tension activated annular repair scaffold (TARS) to treat defects in the annulus fibrosus (AF) associated with herniations, with the goal of closing the annular defect and stimulating native tissue repair to restore disc mechanical function. Three Specific Aims are pursued: Two Specific Aims are pursued: Specific Aim 1: Develop tension-actuated AF repair scaffolds. A novel mechanically activated microcapsule (MAMC) will be included in electrospun scaffolds to create the TARS. Scaffold properties and MAMC attributes will be varied to optimize material fabrication and to tune release in response to tensile loading. We will create two classes of MAMCs: 1) containing chemotactic cell recruitment agents designed to activate under low levels of physiologic loading and 2) matrix-promoting agents housed within MAMCs designed to burst sequentially with long term loading. Both populations will include an anti-inflammatory agent to improve regeneration. Bioactivity of the MAMCs will also be confirmed via in vitro bioreactor assays. Specific Aim 2: Evaluate the TARS in models of intervertebral disc repair under physiologic loading. Box defects in the AF will be created in cadaveric goat spinal motion segments, and the TARS sutured in place. Ex vivo, multi- axial (compression, flexion, extension and torsion) dynamic loading will be applied to demonstrate that physiologic spinal loading causes sequential release from the two MAMC populations. Outcomes will include confocal microscopy analysis of MAMC release and analysis of motion segment mechanical properties. Next, we will carry out a pilot study in our goat cervical spine model in which the in vivo repair capacity of the TARS will be evaluated. Outcomes at 3 months will include histological analysis of the scaffold and cell infiltration and MRI and mechanical properties of the repaired motion segment.It is anticipated that the proposed study will yield a novel repair for defects of the AF and an increased understanding of the mechanobiology of the IVD. This novel treatment may decrease the risk of recurrent herniations and offer a new clinical paradigm.

每年有 0.5% 至 2% 的成年人出现有症状的腰椎间盘突出症，其中 在工作环境中从事剧烈活动的个人的发病率较高，包括 现役军人。腰椎显微椎间盘切除术对于解决以下问题非常有效 挤压椎间盘碎片并减轻根性腿部疼痛。不过，目前还没有 建立了修复环形缺陷的方法。受伤的纤维环已经改变 机械性能，并且众所周知，较大的环形缺陷与 该间隙复发椎间盘突出的风险增加。随着自动对焦功能的丧失， 运动节段也面临进一步退化、椎间盘间隙高度损失和进一步退化的风险。 退变是腰椎间盘突出症常见的后遗症。目前还没有有效的 旨在以概括的方式修复纤维环的临床干预措施 原生光盘。该项目的目标是开发一种新型张力激活环形修复装置 支架（TARS）治疗与疝气相关的纤维环（AF）缺陷， 闭合环形缺损并刺激天然组织修复以恢复椎间盘机械性能的目标 功能。追求三个具体目标： 追求两个具体目标： 具体目标 1： 开发张力驱动的房颤修复支架。一种新型机械活化微胶囊 (MAMC) 将包含在电纺支架中以创建 TARS。脚手架特性和 MAMC 属性将有所不同，以优化材料制造并调整释放以响应 拉伸载荷。我们将创建两类 MAMC：1) 包含趋化细胞募集 设计用于在低水平生理负荷下激活的药物和 2) 基质促进剂 药剂容纳在 MAMC 内，设计为长期负载时顺序爆裂。两个都 人群将包含抗炎剂以改善再生。的生物活性 MAMC 还将通过体外生物反应器测定进行确认。具体目标 2：评估 TARS 在生理负荷下的椎间盘修复模型中。 AF 中的盒子缺陷将是 在尸体山羊脊柱运动节段中创建，并将 TARS 缝合到位。离体、多 将应用轴向（压缩、弯曲、伸展和扭转）动态载荷来演示 生理脊柱负荷导致两个 MAMC 群体依次释放。 结果将包括 MAMC 释放的共焦显微镜分析和运动分析 段机械性能。接下来，我们将在山羊颈椎中进行试点研究 将评估 TARS 体内修复能力的模型。 3个月的结果 将包括支架和细胞浸润的组织学分析以及 MRI 和机械分析 修复后的运动段的特性。预计所提出的研究将产生 对 AF 缺陷的新颖修复以及对 AF 机械生物学的更多了解 体外诊断。这种新颖的治疗方法可能会降低疝气复发的风险，并提供新的临床治疗方法 范例。