Renerva, LLC, Pittsburgh, Pennsylvania, USA.
Department of Biomedical Sciences, Section of Anatomic Pathology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
J Biomed Mater Res A. 2022 Nov;110(11):1738-1748. doi: 10.1002/jbm.a.37437. Epub 2022 Aug 17.
Neuroma formation following limb amputation is a prevalent and debilitating condition that can deeply affect quality of life and productivity. Several approaches exist to prevent or treat neuromas; however, no approach is either consistently reliable or surgically facile, with high rates of neuroma occurrence and/or recurrence. The present study describes the development and testing of a xenogeneic nerve cap graft made from decellularized porcine nerve. The grafts were tested in vitro for cellular removal, cytotoxicity, mechanical properties, and morphological characteristics. The grafts were then tested in rat sciatic nerve gap reconstruction and nerve amputation models for 8 weeks. Gross morphology, electrophysiology, and histopathology assessments were performed to determine the ability of the grafts to limit pathologic nerve regrowth. In vitro testing showed well decellularized and demyelinated nerve cap graft structures without any cytotoxicity from residual reagents. The grafts had a proximal socket for the proximal nerve stump and longitudinally oriented internal pores. Mechanical and surgical handling properties suggested suitability for implantation as a nerve graft. Following 8 weeks in vivo, the grafts were well integrated with the proximal and distal nerve segments without evidence of fibrotic adhesions to the surrounding tissues or bulbous outgrowth of the nerve. Electrophysiology revealed absence of nerve conduction within the remodeled nerve cap grafts and significant downstream muscle atrophy. Histologic evaluation showed well organized but limited axonal regrowth within the grafts without fibrous overgrowth or neuromatous hypercellularity. These results provide proof of concept for a novel xenograft-based approach to neuroma prevention.
肢体截肢后神经瘤的形成是一种普遍且使人虚弱的病症，会严重影响生活质量和生产力。目前有几种方法可以预防或治疗神经瘤；然而，没有一种方法既可靠又易于手术，神经瘤的发生率和/或复发率都很高。本研究描述了一种由去细胞化猪神经制成的异种神经帽移植物的开发和测试。对移植物进行了体外细胞去除、细胞毒性、机械性能和形态特征测试。然后将移植物在大鼠坐骨神经间隙重建和神经切断模型中进行了 8 周的测试。进行了大体形态、电生理学和组织病理学评估，以确定移植物限制病理性神经再生的能力。体外测试显示，去细胞化和脱髓鞘的神经帽移植物结构良好，没有残留试剂的细胞毒性。移植物具有用于近端神经残端的近端插座和纵向取向的内部孔。机械和手术处理特性表明适合作为神经移植物植入。在体内 8 周后，移植物与近端和远端神经段很好地整合在一起，没有与周围组织发生纤维粘连或神经呈球状膨出的迹象。电生理学显示，在重塑的神经帽移植物内没有神经传导，并且下游肌肉明显萎缩。组织学评估显示，移植物内的轴突有很好的组织，但再生有限，没有纤维过度生长或神经瘤样细胞过度增生。这些结果为预防神经瘤的新型异种移植物方法提供了概念验证。
