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Multi-factorial nerve guidance conduit engineering improves outcomes in inflammation, angiogenesis and large defect nerve repair
Matrix Biology ( IF 6.9 ) Pub Date : 2022-01-13 , DOI: 10.1016/j.matbio.2022.01.002
Alan J Hibbitts 1 , Zuzana Kočí 1 , Simone Kneafsey 1 , Amos Matsiko 1 , Leyla Žilić 1 , Adrian Dervan 1 , Paige Hinton 1 , Gang Chen 2 , Brenton Cavanagh 3 , Jennifer K Dowling 4 , Claire E McCoy 4 , Conor T Buckley 1 , Simon J Archibald 5 , Fergal J O'Brien 1
Affiliation  

Nerve guidance conduits (NGCs) are sub-optimal for long-distance injuries with inflammation and poor vascularization related to poor axonal repair. This study used a multi-factorial approach to create an optimized biomaterial NGC to address each of these issues. Through stepwise optimization, a collagen-chondroitin-6-sulfate (Coll-CS) biomaterial was functionalized with extracellular matrix (ECM) components; fibronectin, laminin 1 and laminin 2 (FibL1L2) in specific ratios. A snap-cooled freeze-drying process was then developed with optimal pore architecture and alignment to guide axonal bridging. Culture of adult rat dorsal root ganglia on NGCs demonstrated significant improvements in inflammation, neurogenesis and angiogenesis in the specific Fib:L1:L2 ratio of 1:4:1. In clinically relevant, large 15 mm rat sciatic nerve defects, FibL1L2-NGCs demonstrated significant improvements in axonal density and angiogenesis compared to unmodified NGCs with functional equivalence to autografts. Therefore, a multiparameter ECM-driven strategy can significantly improve axonal repair across large defects, without exogenous cells or growth factors.



中文翻译:

多因素神经引导导管工程改善炎症、血管生成和大缺损神经修复的结果

神经引导导管 (NGC) 对于伴有炎症和与轴突修复不良相关的血管化不良的远距离损伤来说不是最佳选择。本研究使用多因素方法来创建优化的生物材料 NGC,以解决这些问题。通过逐步优化,胶原-6-硫酸软骨素 (Coll-CS) 生物材料被细胞外基质 (ECM) 成分功能化;特定比例的纤连蛋白、层粘连蛋白 1 和层粘连蛋白 2 (FibL1L2)。然后开发了一种快速冷却的冷冻干燥工艺,具有最佳的孔结构和对齐方式,以指导轴突桥接。在 NGCs 上培养成年大鼠背根神经节,在特定的 Fib:L1:L2 比例为 1:4:1 时,在炎症、神经发生和血管生成方面表现出显着改善。在临床相关的 15 毫米大大鼠坐骨神经缺损中,与功能等同于自体移植物的未修饰 NGC 相比,FibL1L2-NGC 在轴突密度和血管生成方面表现出显着改善。因此,多参数 ECM 驱动的策略可以显着改善大缺陷的轴突修复,而无需外源细胞或生长因子。

更新日期:2022-02-04
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