Department of Biological Sciences and Bioengineering , Indian Institute of Technology Kanpur , Kanpur , 208016 Uttar Pradesh , India.
Department of Chemical and Metallurgical Engineering, School of Chemical Engineering , Aalto University , Helsinki , Finland.
Biomacromolecules. 2019 Feb 11;20(2):662-673. doi: 10.1021/acs.biomac.8b01308. Epub 2018 Nov 2.
Recent trends in peripheral nerve regeneration are directed toward the development of nerve guidance channels to assist the regeneration of the nerves across critical size defects. Advanced nerve guidance channels (aNGCs) should possess multifunctional properties to direct the axonal regeneration from proximal to distal end, allow the concentration of growth factors secreted by the injured nerve end, and attenuate the ingrowth of scar tissue at the site of injury. The design of the nerve guidance channel (NGC) is critical for providing the necessary topographical, chemotactic, as well as haptotactic cues for efficient nerve regeneration. In this study, we have designed and fabricated clinically relevant aNGCs comprising an antioxidant polyurethane (PUAO) conduit filled with aligned chitosan-gelatin (CG) cryogel filler for peripheral nerve regeneration. The effects of temperature, polymer concentration, and cross-linker concentration on the physicochemical properties of the CG cryogel filler were studied. The synthesized scaffolds were evaluated by scanning electron microscopy (SEM) and compression testing to obtain the matrix best suited to form the aNGC. The nanofibrous PUAO conduit was fabricated by electrospinning with a wall thickness of 114.16 ± 26.91 μm, which was filled with CG (1.2/6.4%)-aligned cryogel matrix to obtain the aNGCs. The aNGCs with 2.01 ± 0.04 mm internal diameter, 15 mm length, and internal CG filler with a pore diameter of 29.60 ± 9.83 μm were fabricated. The aNGCs were evaluated by SEM and in vitro neuronal culture for biocompatibility and cellular alignment. In vitro dorsal root ganglion cultures showed the aligned growth and cellular migration along the aligned pores of aNGCs. With this study, we conclude that this clinically relevant aligned porous aNGC will have a promising effect in repair and regeneration of peripheral nerve injuries.
近年来，周围神经再生的趋势是开发神经引导通道，以帮助跨临界尺寸缺陷的神经再生。先进的神经引导通道 (aNGC) 应该具有多功能特性，从近端到远端引导轴突再生，允许受伤神经末端分泌的生长因子集中，并减轻损伤部位疤痕组织的向内生长。神经引导通道 (NGC) 的设计对于提供有效的神经再生所需的拓扑、趋化和贴壁线索至关重要。在这项研究中，我们设计并制造了包含抗氧化聚氨酯 (PUAO) 导管和填充有定向壳聚糖-明胶 (CG) 水凝胶填充剂的临床相关 aNGC，用于周围神经再生。研究了温度、聚合物浓度和交联剂浓度对 CG 水凝胶填充剂理化性质的影响。通过扫描电子显微镜 (SEM) 和压缩测试评估合成支架，以获得最适合形成 aNGC 的基质。通过静电纺丝制造纳米纤维 PUAO 导管，其壁厚为 114.16 ± 26.91 μm，填充 CG（1.2/6.4%）定向水凝胶基质以获得 aNGC。制造出内径为 2.01 ± 0.04 mm、长度为 15 mm、内部 CG 填充剂孔径为 29.60 ± 9.83 μm 的 aNGC。通过 SEM 和体外神经元培养评估 aNGC 的生物相容性和细胞排列。体外背根神经节培养显示，沿着 aNGC 的定向孔呈定向生长和细胞迁移。通过这项研究，我们得出结论，这种临床相关的定向多孔 aNGC 将在周围神经损伤的修复和再生中具有广阔的应用前景。
