ENT and Head & Neck Research Center and Department, The Five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Polymer Engineering Department, Faculty of Engineering, Urmia University, Urmia, Iran.
Carbohydr Polym. 2019 Nov 15;224:115161. doi: 10.1016/j.carbpol.2019.115161. Epub 2019 Aug 8.
Electroactive scaffolds derived from carbohydrate hydrogels were synthesized, resulting in a large shift in the conductivity of chitosan (CS) from 10 S/cm to about 10 S/cm, assigned to CS-oligoaniline. Several analyses including UV-vis spectroscopy and cyclic voltammetry were performed, before examining the carbohydrate-based scaffolds for their ability to recapitulate the neural tissue microenvironment. Good conductivity and resemblance of the modulus to soft tissue of the optimized hydrogels led to appropriate cellular activity and neural regeneration. The loss of dopaminergic neurons as the prominent source of dopamine in the central nervous system results in the deterioration of multiple brain functions such as voluntary movement and behavioral processes. To overcome this, olfactory ecto-mesenchymal stem cells (OE-MSCs) were induced to differentiate into dopaminergic neuron-like cells on hydrogels through a monolayer arrangement cell culture by using cocktail neurotrophic factors including sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF), glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). The differentiation capacity of a series of OE-MSCs on the conductive hydrogel was evaluated by real-time PCR, immunocytochemistry and flow cytometry, and the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) neural and dopaminergic markers. The results of this study represent the first steps in designing and implementing advanced platforms based on conductive polysaccharide hydrogels for neural disorder therapies, such as the treatment of Parkinson's disease.
基于碳水化合物水凝胶的电活性支架被合成,导致壳聚糖 (CS) 的电导率从 10 S/cm 大幅增加到约 10 S/cm,归因于 CS-寡聚苯胺。进行了包括紫外可见光谱和循环伏安法在内的几种分析,然后检查了基于碳水化合物的支架复制神经组织微环境的能力。优化水凝胶具有良好的导电性和与软组织相似的模量,从而导致适当的细胞活性和神经再生。多巴胺能神经元作为中枢神经系统中多巴胺的主要来源的丧失会导致多种大脑功能(如自主运动和行为过程)恶化。为了克服这一问题,通过使用包括 sonic hedgehog (SHH)、成纤维细胞生长因子 8 (FGF8)、碱性成纤维细胞生长因子 (bFGF)、胶质细胞源性神经营养因子 (GDNF) 和脑源性神经营养因子 (BDNF) 在内的鸡尾酒神经营养因子,将嗅外间充质干细胞 (OE-MSCs) 在水凝胶上诱导单层排列细胞培养分化为多巴胺能神经元样细胞。通过实时 PCR、免疫细胞化学和流式细胞术评估了一系列 OE-MSCs 在导电水凝胶上的分化能力,并检测了酪氨酸羟化酶 (TH) 和多巴胺转运蛋白 (DAT) 神经和多巴胺能标志物的表达。这项研究的结果代表了基于导电多糖水凝胶设计和实施神经紊乱治疗先进平台的第一步,例如帕金森病的治疗。
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