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: 10117756
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117756
• 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; 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; Services; Site; Spinal; Spine surgery; Strenuous Exercise; Structure; Surgical sutures; Symptoms; System; Technology; Testing; Thick; Thinness; Time; Tissue Engineering; Tissues; Torsion; Vertebral column; Veterans; Weight-Bearing state; Work; clinical practice; design; experience; implantation; improved; in vivo; in vivo Model; injured; joint mobilization; mechanical load; mechanical properties; novel; preservation; professional atmosphere; recruit; release factor; 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发生在每年0.5至2％的成人人群中， 在其工作环境中暴露于剧烈活动的个人的发病率更高，包括 现役军事人员。腰椎切除术非常有效地解决 挤出的椎间盘碎片和减轻根部的腿部疼痛。但是，目前没有 修复环形缺陷的建立方法。受伤的环纤维已改变 机械性能，并且众所周知，较大的环形缺陷与 在该空间上，椎间盘催眠的复发风险增加。随着AF功能的这种损失， 运动段也有进一步退化的风险，椎间盘空间高度的损失和进一步 变性是腰椎间盘突出症的常见后遗症。目前没有效力 临床干预措施针对修复环纤维的临床干预措施以概括性的方式 本机光盘。该项目的目的是开发一种新型的张力激活环形修复 脚手架（tars）处理与疝的环形纤维（AF）中的缺陷， 关闭环形缺陷和刺激天然组织修复以恢复圆盘机械的目标 功能。提出了三个具体目标：实现了两个具体目标：具体目标1： 开发张力的AF修复支架。一种新型机械激活的微胶囊 （MAMC）将包含在电纺支架中以创建焦油。脚手架特性和 MAMC属性将有所不同，以优化材料制造并响应于 拉伸负荷。我们将创建两类MAMC：1）包含趋化细胞募集 旨在在低水平的生理负荷下激活的代理和2）促进矩阵 装置在MAMC中的代理，旨在依次与长期载荷爆裂。两个都 种群将包括一种抗炎药以改善再生。生物活性 MAMC也将通过体外生物反应器测定得到确认。特定目标2：评估焦油 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段中创建，焦油缝合到位。 ex vivo，多 将应用轴向（压缩，屈曲，延伸和扭转）动态载荷以证明 该生理性脊柱负荷导致两个MAMC种群的顺序释放。 结果将包括MAMC释放的共聚焦显微镜分析和运动分析 段机械性能。接下来，我们将在山羊颈椎进行试点研究 将评估焦油的体内维修能力的模型。 3个月的结果 将包括对支架和细胞浸润以及MRI和机械的组织学分析 修复的运动段的特性。预计拟议的研究将产生 新的修复AF缺陷以及对机械生物学的越来越多的理解 IVD。这种新颖的治疗可能会降低复发性疝的风险，并提供新的临床 范例。