【作者】 陈晓燕；

【导师】 柴人杰；

【作者基本信息】 东南大学 ， 生物学， 2022， 硕士

【摘要】 脊髓损伤是当今中枢神经系统损伤的重要一类,其治疗一直是基础和临床医学研究的难点。目前许多药物已被证明具有促进神经再生修复的作用,如神经营养因子、神经节苷脂等。但由于这些因子的半衰期较短,在较长时间的神经修复中很难保证药物浓度的稳定性,传统的外周静脉给药方式难以实施。因此,设计一种具有理想的受控给药性能且在临床有潜在应用价值的缓释体系是目前较为紧迫的问题。在这里,为了达到预期的效果,我们提出了一种载FGF因子的Gel MA水凝胶微球,能够较长久地维持高浓度的药物活性成分,延长药物作用时间,并初步证实其在脊髓损伤神经修复中的积极作用。Gel MA水凝胶具有良好的生物相容性,在组织工程领域得到了广泛的应用。同时,得益于微流控技术精确的液滴操纵能力,制备的微球具有均匀、令人满意的尺寸和良好的稳定性。更重要的是,Gel MA水凝胶与微球的有利结合,既可以达到药物在靶部位集中发挥作用的目的,也可以凭借微球的尺寸优势及可注射性尽可能的减小对其他组织细胞的毒副作用。此外,通过体外药物释放实验,分析表明该负载微球可以释放药物长达20天以上,并能保持良好的药物活性。且与神经干细胞的体外共培养,发现该负载微球能够有效地促进神经干细胞的增殖和分化。在大鼠脊髓损伤模型中,通过相关组织学分析及BBB评分我们证实了载FGF的Gel MA微球可以有效促进神经再生及运动功能的恢复,揭示了其在中枢神经系统损伤修复以及更多的医学领域存在广泛的应用前景。更多还原

【Abstract】 Spinal cord injury(SCI)is a serious central nervous system injury(CNS),and its treatment has always been a difficulty in basic and clinical medical research.Many drugs have been proved to have the function of treating SCI,such as neurotrophic factors,gangliosides and so on.However,due to the short half-life of these factors,it is difficult to ensure the stability of the concentration in a long time of nerve repair,so it is difficult to implement peripheral intravenous administration.Here,in order to ensure the efficacy of nutritional factors and achieve the desired effect,we propose a fibroblast growth factors(FGF)-loaded Gel MA hydrogel microspheres with ideal performance for controlled drug delivery and spinal cord injury repair.In particular,the microspheres derived from natural polymer materials possess good biocompatibility,thus playing important roles in drug delivery,tissue engineering,etc.At the same time,with the help of microfluidic technology,the microsphere carrier with uniform size and good stability was obtained.More importantly,thanks to the porous structure of Gel MA microspheres,drugs and active molecules are easier to enter and protected from active enzymes in vivo.In addition,by co-culture with neural stem cells in vitro,it was found that the FGF-loaded Gel MA microspheres could effectively promote NSCs proliferation and differentiation.We also proved the positive role of the FGF-loaded Gel MA microspheres in nerve repair of spinal cord injury in rats,which may have potential value for application in repairing central nervous system injuries.更多还原