Wang Pangbo, Wang Hufei, Ma Kang, Wang Shi, Yang Chuanyan, Mu Ning, Yang Fei, Feng Hua, Chen Tunan
Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University) Chongqing 400038 China
Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry Chinese Academy of Sciences Beijing 100190 China.
RSC Adv. 2020 Feb 11;10(11):6306-6314. doi: 10.1039/c9ra10385f. eCollection 2020 Feb 7.
Severe spinal cord injury (SCI) always leads to permanent sensory and motor dysfunction. However, the therapeutic effects of current treatment methods, including high dose methylprednisolone, surgical interventions and rehabilitative care, are far from satisfactory. In recent years, cellular, molecular, tissue engineering and rehabilitative training have shown promising results in animal models. Poly-ε-caprolacton (PCL) - based hydrogel composite system has been considered as a promising strategy to direct the axon growth and mimic the properties of natural extracellular matrix. In this study, we found the addition of the fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) to the hydrogel induces the production of axon growth-supportive substrates. The addition of the glial-derived neurotrophic factor (GDNF) to the hydrogel further induces axon directional growth. This "five-in-one" composite scaffold, referred to as PCL/PEG/FGF2/EGF/GDNF, improved the locomotor function in rats 8 weeks after spinal cord injury (SCI) after implantation in transected spinal cord. Furthermore, histological assessment indicated that the designed composite scaffold guided the neuronal regeneration and promoted the production of axon growth-supportive substrates, providing a favorable biological microenvironment. Our novel composite scaffold provides a promising therapeutic method for SCI.
严重脊髓损伤(SCI)总会导致永久性感觉和运动功能障碍。然而,包括大剂量甲基强的松龙、手术干预和康复护理在内的当前治疗方法的治疗效果远不尽人意。近年来,细胞、分子、组织工程和康复训练在动物模型中已显示出有前景的结果。基于聚-ε-己内酯(PCL)的水凝胶复合系统已被视为一种有前景的策略,用于引导轴突生长并模拟天然细胞外基质的特性。在本研究中,我们发现向水凝胶中添加成纤维细胞生长因子2(FGF2)和表皮生长因子(EGF)可诱导产生支持轴突生长的底物。向水凝胶中添加胶质细胞源性神经营养因子(GDNF)可进一步诱导轴突定向生长。这种“五合一”复合支架,称为PCL/PEG/FGF2/EGF/GDNF,在植入横断脊髓后8周改善了脊髓损伤(SCI)大鼠的运动功能。此外,组织学评估表明,设计的复合支架引导神经元再生并促进支持轴突生长的底物的产生,提供了有利的生物微环境。我们的新型复合支架为SCI提供了一种有前景的治疗方法。