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Internal decompression of the acutely contused spinal cord: Differential effects of irrigation only versus biodegradable scaffold implantation
Biomaterials ( IF 14.0 ) Pub Date : 2018-09-19 , DOI: 10.1016/j.biomaterials.2018.09.025
James D. Guest , Simon W. Moore , Alex A. Aimetti , Artem B. Kutikov , Andrea J. Santamaria , Christoph P. Hofstetter , Alexander E. Ropper , Nicholas Theodore , Thomas R. Ulich , Richard T. Layer

Severe spinal cord injury leads to hemorrhage, edema and elevated tissue pressures that propagate ischemia. Liquefactive necrosis of damaged tissue eventually results in chronic cavities due to a wound healing process lacking adhesive contractile cells. Biomaterials can potently influence wound healing responses. Internal decompression (ID) refers to pial opening, allowing spontaneous extrusion and irrigation of fluid necrotic debris relieving pressure and resulting in a space for biomaterial scaffold insertion. After thoracic contusions, rats were randomized to: contusion only, contusion + ID and contusion + ID + PLGA-PLL scaffold implantation, to test for neuroprotection and endogenous repair over 3 months. ID alone reduced inflammatory activity, cavity volume, and increased tissue sparing. Scaffold biodegradation produced delayed ingrowth of inflammatory and other cells resulting in endogenously derived laminin-rich tissue, marked reduction in cavitation and presence of tissue remodeling macrophages. Extensive recruitment of Schwann cells into adjacent spared white matter occurred, greatest in scaffold-implanted animals. Despite tissue preservation with myelin repair, no groups differed significantly in open field locomotion. However, across all rats, spared epicenter tissue and locomotor outcomes were correlated. Scaffold-implanted animals showed no obvious toxicity. To study the clinical feasibility, timing and indications for scaffold implantation, Göttingen minipigs underwent ID and were implanted with scaffolds 4, 6, and 24 h after T10 contusion. High intra-spinal tissue pressures fell to pre-injury levels after ID and scaffold implantation. Extrusion of necrotic debris left sufficient space for a sized scaffold. These results provided the preclinical rationale for a current clinical study of biomaterial scaffold implantation into the human injured spinal cord.



中文翻译:

急性挫伤性脊髓的内部减压:仅冲洗与可生物降解支架植入的差异作用

严重的脊髓损伤会导致出血,水肿和组织压力升高,从而加剧局部缺血。受损组织的液化坏死最终导致慢性空洞,这是由于伤口愈合过程缺乏粘附性收缩细胞所致。生物材料可以有效地影响伤口的愈合反应。内部减压(ID)指的是打开颈椎,允许自发性挤压冲洗坏死的液体碎片可以减轻压力,并为生物材料支架的插入提供空间。胸挫伤后,将大鼠随机分为:仅挫伤,挫伤+ ID和挫伤+ ID + PLGA-PLL支架植入,以测试3个月内的神经保护和内源性修复。单独使用ID可以减少炎症活动,减少腔体积并增加组织备用。支架的生物降解导致炎性细胞和其他细胞的向内生长延迟,从而导致内源性富含层粘连蛋白的组织,明显的空化减少和组织重塑巨噬细胞的存在。雪旺氏细胞大量募集到邻近的剩余白质中,在植入支架的动物中最大。尽管通过髓鞘修复保存了组织,但在野外运动中没有任何组有显着差异。然而,在所有大鼠中,多余的震中组织与运动结局相关。植入支架的动物没有明显的毒性。为了研究支架植入的临床可行性,时机和适应症,对Göttingen小型猪进行ID,并在T10挫伤后4、6和24 h植入支架。内径和支架植入后,高椎管内组织内压力降至损伤前水平。坏死碎片的挤出留出了足够的空间来放置一个大小合适的支架。这些结果为目前将生物材料支架植入人受伤的脊髓的临床研究提供了临床前基础。支架植入的时间和适应症,对Göttingen小型猪进行ID,并在T10挫伤后4、6和24 h植入支架。内径和支架植入后,高椎管内组织内压力降至损伤前水平。坏死碎片的挤出留出了足够的空间来放置一个大小合适的支架。这些结果为目前将生物材料支架植入人受伤的脊髓的临床研究提供了临床前基础。支架植入的时间和适应症,对Göttingen小型猪进行ID,并在T10挫伤后4、6和24 h植入支架。内径和支架植入后,高椎管内组织内压力降至损伤前水平。坏死碎片的挤出留出了足够的空间来放置一个大小合适的支架。这些结果为目前将生物材料支架植入人受伤的脊髓的临床研究提供了临床前基础。

更新日期:2018-09-20
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