Department of Chemical and Biomolecular Engineering, Clarkson University, Potsdam, NY 13699.
Clarkson University.
J Biomech Eng. 2024 Nov 1;146(11). doi: 10.1115/1.4066071.
Intradiscal injection is required to deliver therapeutic agents to the intervertebral disc (IVD) nucleus pulposus (NP). However, injectate leakage following needle retraction may result in decreased treatment efficacy and adverse side effects. While enzymatic digestion is a common research approach for simulating degeneration in healthy animal IVDs, contributions to the leakage phenomenon are unknown. In this study, bovine caudal discs were treated with injection into the NP of either a tris buffer control, collagenase (to primarily target collagen), or trypsin (to primarily target proteoglycans) and then injected with fluorescent saline using a through-puncture defect protocol. Pressure-volume records during injection were used to determine volume and pressure at leakage. Discs were then frozen, transected, and photographed to visualize injectate dispersion. Collagenase treatment resulted in a large increase in injectate dispersion, along with a decrease in injection pressure relative to control. Trypsin treatment resulted in a moderate increase in dispersion, with no associated effect on pressure. This study concludes that care should be taken when employing enzymatic digestion to simulate IVD degeneration, as NP tissue disruption may affect both retention and dispersion of subsequent therapeutic injections.
椎间盘内注射是将治疗剂递送至椎间盘(IVD)髓核的必需手段。然而,针回缩后注射剂泄漏可能导致治疗效果降低和不良反应。虽然酶消化是模拟健康动物 IVD 退变的常用研究方法,但对泄漏现象的贡献尚不清楚。在这项研究中,通过经皮穿刺缺损方案,向牛尾椎间盘的 NP 中注射三羟甲基氨基甲烷缓冲液对照物、胶原酶(主要针对胶原蛋白)或胰蛋白酶(主要针对蛋白聚糖),然后用荧光盐水进行注射。注射过程中的压力-容积记录用于确定泄漏时的体积和压力。然后将椎间盘冷冻、横切并拍照以可视化注射剂的分散情况。胶原酶处理导致注射剂分散大量增加,同时与对照相比,注射压力降低。胰蛋白酶处理导致分散适度增加,对压力没有影响。本研究得出结论,在使用酶消化模拟 IVD 退变时应谨慎,因为 NP 组织破坏可能会影响随后治疗性注射的保留和分散。