Network of Excellence for Functional Biomaterials (NFB), National University of Ireland, Galway, Ireland.
Tissue Eng Part C Methods. 2010 Dec;16(6):1585-96. doi: 10.1089/ten.TEC.2010.0152. Epub 2010 Jul 13.
In the absence of donor tissues, conduits are needed for axons to regenerate across nerve defects, yet single-channel conduits may result in axonal dispersion, and multichannel synthetic polymer conduits have failed due to dimensional instability. The goal of this study was to create a robust collagen-based nerve conduit with multiple submillimeter-diameter channels to facilitate nerve guidance. Toward this goal, we have developed a novel multistep molding technique to create single-, four-, and seven-channel conduits from collagen and examined the effects of crosslinking with 0-60 mM (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide [EDC] in N-hydroxysuccinimide) on geometric, enzymatic, and thermal stability, mechanical properties, and cellular behavior. Multichannel collagen conduits crosslinked with 30 mM EDC and 10 mM N-hydroxysuccinimide demonstrated low degradation rate (∼10% at 2 days), high shrinkage temperature (>75°C), and constant channel morphology out to 30 days in saline. Neurite outgrowth remained unaffected from cultured dorsal root ganglia explants seeded on collagen scaffolds with up to 30 mM EDC crosslinking. Compared with single-channel conduits, multichannel collagen conduits showed superior structural compressive, tensile, and bending stiffness. Taken together, these results suggest that the crosslinked multichannel collagen conduits possess favorable material and mechanical properties for nerve regeneration applications.
在缺乏供体组织的情况下，需要导管来使轴突跨越神经缺损处再生，但单通道导管可能导致轴突分散，而多通道合成聚合物导管由于尺寸不稳定而失败。本研究的目的是创建一种具有多个亚毫米直径通道的稳健胶原基神经导管，以促进神经导向。为此，我们开发了一种新颖的多步成型技术，从胶原蛋白中创建单通道、四通道和七通道导管，并研究了用 0-60 mM（1-乙基-3-（3-二甲基氨基丙基）碳二亚胺[EDC]在 N-羟基琥珀酰亚胺）交联对几何形状、酶和热稳定性、机械性能和细胞行为的影响。用 30 mM EDC 和 10 mM N-羟基琥珀酰亚胺交联的多通道胶原导管降解率低（2 天约 10%），热收缩温度高（>75°C），在盐水中 30 天内通道形态保持不变。用高达 30 mM EDC 交联的胶原蛋白支架培养的背根神经节外植体，其神经突生长不受影响。与单通道导管相比，多通道胶原导管具有更好的结构抗压、拉伸和弯曲刚度。综上所述，这些结果表明交联的多通道胶原导管具有用于神经再生应用的有利的材料和机械性能。
