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.

有症状的腰椎间盘突出症每年在0.5%到2%的成年人中发生， 在工作环境中从事剧烈活动的个人发病率较高，包括 现役军人。腰椎微创髓核摘除术在解决腰椎间盘突出症方面非常有效 突出的椎间盘碎片和缓解神经根性腿痛。然而，目前还没有 建立了修复环状缺损的方法。受伤的纤维环已经改变 力学性能，众所周知，较大的环状缺陷与 增加了在该间隙复发的风险。随着房颤功能的丧失， 运动节段也有进一步退变的风险，以及椎间盘间隙高度的损失和进一步 退变是腰椎间盘突出症的常见后遗症。目前还没有有效的 以修复纤维环为目标的临床干预措施 本机光盘。本项目的目标是开发一种新型的张力激活的环状修补术 支架(TARS)用于治疗纤维环(AF)中与突出相关的缺陷，与 闭合环状缺损和刺激自然组织修复以恢复椎间盘机械的目标 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。一种新型的机械激活微胶囊 (MAMC)将被包括在电纺支架中，以创建TARS。脚手架属性和 MAMC属性将不同，以优化材料制造并调整释放，以响应 拉伸载荷。我们将创造两类MAMCs：1)含有趋化细胞募集 设计用于在低生理负荷和2)促进基质的情况下激活的制剂 存放在MAMC中的代理设计为在长期负载下按顺序破裂。两者都有 人群中将包括一种消炎剂，以促进再生。人参皂苷的生物活性 MAMCs也将通过体外生物反应器试验得到确认。具体目标2：评估TARS 在生理负荷下的椎间盘修复模型中。房协中的包厢缺陷将是 建立在身体山羊脊柱运动节段，TARS缝合到位。体外，多个 将应用轴向(压缩、弯曲、拉伸和扭转)动态加载来演示 生理脊柱负荷导致两个MAMC群体的顺序释放。 结果将包括MAMC释放的共聚焦显微镜分析和运动分析 管段机械特性。接下来，我们将在我们的山羊颈椎上进行一项初步研究 将评估TARS体内修复能力的模型。3个月后的结果 将包括支架的组织学分析和细胞渗透以及核磁共振和机械 修复的运动片段的属性。预计拟议的研究将产生 房颤修复的新方法和对房颤机制生物学的进一步了解 IVD。这种新的治疗方法可以降低复发的风险，并提供了一种新的临床治疗方法。 范例。