Neural Repair and Biomaterials Laboratory, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda S-N, 45071 Toledo, Spain.
Int J Mol Sci. 2023 Jul 5;24(13):11102. doi: 10.3390/ijms241311102.
Biomaterials may enhance neural repair after spinal cord injury (SCI) and testing their functionality in large animals is essential to achieve successful clinical translation. This work developed a porcine contusion/compression SCI model to investigate the consequences of myelotomy and implantation of fibrin gel containing biofunctionalized carbon microfibers (MFs). Fourteen pigs were distributed in SCI, SCI/myelotomy, and SCI/myelotomy/implant groups. An automated device was used for SCI. A dorsal myelotomy was performed on the lesion site at 1 day post-injury for removing cloths and devitalized tissue. Bundles of MFs coated with a conducting polymer and cell adhesion molecules were embedded in fibrin gel and used to bridge the spinal cord cavity. Reproducible lesions of about 1 cm in length were obtained. Myelotomy and lesion debridement caused no further neural damage compared to SCI alone but had little positive effect on neural regrowth. The MFs/fibrin gel implant facilitated axonal sprouting, elongation, and alignment within the lesion. However, the implant also increased lesion volume and was ineffective in preventing fibrosis, thus precluding functional neural regeneration. Our results indicate that myelotomy and lesion debridement can be advantageously used for implanting MF-based scaffolds. However, the implants need refinement and pharmaceuticals will be necessary to limit scarring.
生物材料可以促进脊髓损伤 (SCI) 后的神经修复,在大型动物中测试其功能对于实现成功的临床转化至关重要。本研究开发了一种猪的挫伤/压迫性 SCI 模型,以研究切开术和植入含有生物功能化碳纤维微纤维 (MFs) 的纤维蛋白凝胶的后果。14 头猪被分配到 SCI、SCI/切开术和 SCI/切开术/植入组。使用自动化装置进行 SCI。在损伤后 1 天,在损伤部位进行背侧切开术,以去除布片和失活组织。用导电聚合物和细胞黏附分子涂覆的 MF 束嵌入纤维蛋白凝胶中,用于桥接脊髓腔。获得了约 1cm 长的可重复损伤。与单纯 SCI 相比,切开术和损伤清创术没有造成进一步的神经损伤,但对神经再生几乎没有积极作用。MFs/纤维蛋白凝胶植入物促进了损伤内轴突的发芽、伸长和排列。然而,植入物也增加了损伤体积,并且不能有效防止纤维化,从而阻止了功能性神经再生。我们的结果表明,切开术和损伤清创术可以有利于植入基于 MF 的支架。然而,植入物需要改进,需要药物来限制瘢痕形成。