Washington University in St. Louis, School of Medicine, Department of Radiology, St. Louis, Missouri, United States.
Washington University in St. Louis, Institute of Materials Science and Engineering, St. Louis, Missouri, United States.
J Biomed Opt. 2022 Jul;27(7):070502. doi: 10.1117/1.JBO.27.7.070502. Epub 2022 Jul 20.
Exogenous extracellular matrix (ECM) proteins, such as fibrinogen and the thrombin-polymerized scaffold fibrin, are used in surgical repair of severe nerve injuries to supplement ECM produced via the injury response. Monitoring the dynamic changes of fibrin during nerve regeneration may shed light on the frequent failure of grafts in the repair of long nerve gaps.
We explored whether monitoring of fibrin dynamics can be carried out using nerve guidance conduits (NGCs) containing fibrin tagged with covalently bound fluorophores.
Fibrinogen was conjugated to a near-infrared (NIR) fluorescent dye. NGCs consisting of silicone tubes filled with the fluorescent fibrin were used to repair a 5-mm gap injury in rat sciatic nerve ( ).
Axonal regeneration in fluorescent fibrin-filled NGCs was confirmed at 14 days after implantation. Intraoperative fluorescence imaging after implantation showed that the exogenous fibrin was embedded in the early stage regenerative tissue. The fluorescent signal temporarily highlighted a cable-like structure within the conduit and gradually degraded over two weeks.
This study, for the first time, visualized intraneural fibrin degradation, potentially a useful prospective indicator of regeneration success, and showed that fluorescent ECM, in this case fibrin, can facilitate imaging of regeneration in peripheral nerve conduits without significantly affecting the regeneration process.
外源性细胞外基质 (ECM) 蛋白，如纤维蛋白原和凝血酶聚合支架纤维蛋白，被用于严重神经损伤的外科修复中，以补充通过损伤反应产生的 ECM。监测纤维蛋白在神经再生过程中的动态变化，可能有助于解释在修复长神经间隙时移植物经常失败的原因。
我们探索了使用含有共价结合荧光团的纤维蛋白标记的神经引导管 (NGC) 是否可以进行纤维蛋白动力学监测。
纤维蛋白原与近红外 (NIR) 荧光染料缀合。使用含有荧光纤维蛋白的硅胶管填充的 NGC 修复大鼠坐骨神经 5 毫米间隙损伤 ( )。
植入后 14 天证实了荧光纤维蛋白填充 NGC 中的轴突再生。植入后的术中荧光成像显示，外源性纤维蛋白被嵌入早期再生组织中。荧光信号暂时突出了导管内的电缆状结构，并在两周内逐渐降解。
本研究首次可视化了神经内纤维蛋白降解，这可能是一个有用的再生成功的前瞻性指标，并表明荧光 ECM（在这种情况下为纤维蛋白）可以促进周围神经导管中再生的成像，而不会显著影响再生过程。
