Mechano-active annular repair device for treating disc herniation

症状性腰椎间盘突出症每年发生在0.5%至2%的成年人群中， 在工作环境中从事剧烈活动的个人发病率较高， 现役军人。腰椎间盘显微切除术对于解决 突出的椎间盘碎片和缓解神经根性腿部疼痛。但目前尚无 建立了修复环状缺损的方法。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 增加了椎间盘突出复发的风险。随着AF功能的丧失， 运动节段也有进一步退化的风险，以及椎间盘间隙高度的损失， 退变是腰椎间盘突出症的常见后遗症。目前还没有有效 旨在修复纤维环的临床干预， 本地磁盘。本项目的目的是开发一种新的张力激活的瓣环修复 支架（TARS）治疗与疝相关的纤维环（AF）缺损， 目的是闭合瓣环缺损并刺激自体组织修复，以恢复椎间盘机械功能 功能三个具体目标：两个具体目标：具体目标1： 开发张力驱动AF修复支架。一种新型机械活化微胶囊 （MAMC）将被包括在静电纺丝支架中以产生TARS。支架性能和 MAMC属性将有所不同，以优化材料制造，并根据 拉伸载荷我们将创建两类MAMCs：1）含有趋化细胞募集 设计用于在低水平生理负荷下活化的试剂和2）基质促进剂 容纳在MAMC内的药剂，其被设计成在长期加载的情况下顺序地破裂。两 群体将包括抗炎剂以改善再生。生物活性 MAMC也将通过体外生物反应器试验进行确认。具体目标2：评估TARS 在生理负荷下的椎间盘修复模型中。AF中的包装盒缺陷将 在尸体山羊脊柱运动节段中创建，并将TARS缝合到位。离体，多- 将施加轴向（压缩、屈曲、伸展和扭转）动态载荷，以证明 生理性脊柱负荷导致两个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 分段机械性能接下来，我们将在我们的山羊颈椎中进行试点研究 模型，其中将评估TARS的体内修复能力。3个月时的结局 将包括支架和细胞浸润的组织学分析以及MRI和机械分析。 修复的运动段的属性。预计拟议的研究将产生一个 新的修复缺陷的AF和增加的理解的机械生物学的 IVD。这种新的治疗方法可以降低复发性疝的风险，并提供一种新的临床治疗方法。 范例

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.