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使用京尼平交联纤维蛋白粘合剂水凝胶修复大鼠椎间盘的体外生物力学研究

Ex-vivo biomechanics of repaired rat intervertebral discs using genipin crosslinked fibrin adhesive hydrogel.

作者信息

Fujii Kengo, Lai Alon, Korda Nimrod, Hom Warren W, Evashwick-Rogler Thomas W, Nasser Philip, Hecht Andrew C, Iatridis James C

机构信息

Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Orthopaedic Surgery, University of Tsukuba, Tsukuba, Japan.

Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

出版信息

J Biomech. 2020 Dec 2;113:110100. doi: 10.1016/j.jbiomech.2020.110100. Epub 2020 Oct 28.

Abstract

Microdiscectomy is the current standard surgical treatment for intervertebral disc (IVD) herniation, however annulus fibrosus (AF) defects remain unrepaired which can alter IVD biomechanical properties and lead to reherniation, IVD degeneration and recurrent back pain. Genipin-crosslinked fibrin (FibGen) hydrogel is an injectable AF sealant previously shown to partially restore IVD motion segment biomechanical properties. A small animal model of herniation and repair is needed to evaluate repair potential for early-stage screening of IVD repair strategies prior to more costly large animal and eventual human studies. This study developed an ex-vivo rat caudal IVD herniation model and characterized torsional, axial tension-compression and stress relaxation biomechanical properties before and after herniation injury with or without repair using FibGen. Injury group involved an annular defect followed by removal of nucleus pulposus tissue to simulate a severe herniation while Repaired group involved FibGen injection. Injury significantly altered axial range of motion, neutral zone, torsional stiffness, torque range and stress-relaxation biomechanical parameters compared to Intact. FibGen repair restored the stress-relaxation parameters including effective hydraulic permeability indicating it effectively sealed the IVD defect, and there was a trend for improved tensile stiffness and axial neutral zone length. This study demonstrated a model for studying IVD herniation injury and repair strategies using rat caudal IVDs ex-vivo and demonstrated FibGen sealed IVDs to restore water retention and IVD pressurization. This ex-vivo small animal model may be modified for future in-vivo studies to screen IVD repair strategies using FibGen and other IVD repair biomaterials as an augment to additional large animal and human IVD testing.

摘要

显微椎间盘切除术是目前治疗椎间盘(IVD)突出的标准外科手术,但纤维环(AF)缺损仍未修复,这可能会改变IVD的生物力学特性,导致再次突出、IVD退变和复发性背痛。京尼平交联纤维蛋白(FibGen)水凝胶是一种可注射的AF密封剂,先前已证明其能部分恢复IVD运动节段的生物力学特性。需要一个突出和修复的小动物模型来评估修复潜力,以便在成本更高的大动物和最终的人体研究之前对IVD修复策略进行早期筛选。本研究建立了一种离体大鼠尾IVD突出模型,并对突出损伤前后以及使用FibGen修复与否的扭转、轴向拉伸-压缩和应力松弛生物力学特性进行了表征。损伤组包括一个环形缺损,随后去除髓核组织以模拟严重突出,而修复组则进行FibGen注射。与完整组相比,损伤显著改变了轴向运动范围、中性区、扭转刚度、扭矩范围和应力松弛生物力学参数。FibGen修复恢复了应力松弛参数,包括有效水力渗透率,表明它有效地封闭了IVD缺损,并且拉伸刚度和轴向中性区长度有改善的趋势。本研究展示了一种使用大鼠尾IVD进行离体研究IVD突出损伤和修复策略的模型,并证明FibGen密封的IVD恢复了保水性和IVD加压。这种离体小动物模型可能会被修改用于未来的体内研究,以筛选使用FibGen和其他IVD修复生物材料的IVD修复策略,作为对额外的大动物和人体IVD测试的补充。

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