Heparin/Growth Factors-Immobilized Aligned Electrospun Nanofibers Promote Nerve Regeneration in Polycaprolactone/Gelatin-Based Nerve Guidance Conduits
Heparin/Growth Factors-Immobilized Aligned Electrospun Nanofibers Promote Nerve Regeneration in Polycaprolactone/Gelatin-Based Nerve Guidance Conduits
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DOI：
10.1007/s42765-022-00244-6
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发表时间：
2022-12-28
影响因子：
16.1
通讯作者：
Ijima, Hiroyuki
中科院分区：
文献类型：
--
作者：
Ikegami, Yasuhiro;Shafiq, Muhammad;Ijima, Hiroyuki
神经系统损伤是全世界普遍存在的发病率、死亡率和不适感的原因。人工神经引导导管(NGCs)为神经重建提供了一个很有前景的平台，但它们需要细胞外基质(ECM)样的特征来更好地模拟体内的微环境。因此，本研究旨在制备肝素/生长因子(GFS)固定化的人工NGCs。将肝素共价固定在电纺聚己内酯/明胶(PCL/Gel)纳米纤维上。此后，碱性成纤维细胞生长因子(BFGF)和神经生长因子(NGF)优先固定在肝素化的纳米纤维上，GFS的固定化效率比(W.r.t.)他们最初的装载量。神经生长因子在坐骨神经缺损处的体内移植实验表明，神经生长因子在体内的存留量(与初始负载量的10%相近)和生物活性长达5天。进一步测试了牛血清白蛋白(BSA)对纳米纤维膜的透过性，发现其与商品化的醋酸纤维素膜相当。在大鼠坐骨神经损伤模型中，短期(1周)和长期(1个月)评价NGCs的生物活性。NGCs在体内表现出良好的结构稳定性和生物相容性。体内评价显示宿主细胞积聚到移植的NGCs中。综上所述，这些肝素/GFS固定的人工NGCs可能对神经再生和相关的组织工程学科具有广泛的意义。
Injuries to the nervous system account for the widespread morbidity, mortality, and discomfort worldwide. Artificial nerve guidance conduits (NGCs) offer a promising platform for nerve reconstruction, however, they require extracellular matrix (ECM)-like features to better mimic the in vivo microenvironment. Consequently, this research was aimed to fabricate heparin/growth factors (GFs)-immobilized artificial NGCs. Heparin was covalently immobilized onto aligned electrospun polycaprolactone/gelatin (PCL/Gel) nanofibers. Thereafter, basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) were preferentially immobilized on heparinized nanofibers; the immobilization efficiency of GFs was found to be 50% with respect to (w.r.t.) their initial loaded amounts. The in vivo implantation of NGCs in a sciatic nerve defect model revealed the successful retention (similar to 10% w.r.t the initial loaded amount) and bioactivity of NGF for up to 5 days. The permeability of bovine serum albumin (BSA) from nanofibrous membranes was further assessed and found to be comparable with the commercialized cellulose acetate membranes. The bioactivity of NGCs was assessed in a sciatic nerve defect model in rats for short-term (1 week) and long-term (1-month). The NGCs displayed good structural stability and biocompatibility in vivo. The in vivo evaluation revealed the accumulation of host cells into the transplanted NGCs. Taken together; these heparin/GFs-immobilized artificial NGCs may have broad implications for nerve regeneration and related tissue engineering disciplines.