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每年发生在0.5 - 2%的成年人中