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首页> 外文期刊>Materials science & engineering >A tuned gelatin methacryloyl (GelMA) hydrogel facilitates myelination of dorsal root ganglia neurons in vitro
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A tuned gelatin methacryloyl (GelMA) hydrogel facilitates myelination of dorsal root ganglia neurons in vitro

机译：调节明胶甲基丙烯酰（GELMA）水凝胶促进体外背根神经节神经元的髓鞘髓鞘

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摘要

Investigating axonal myelination by Schwann cells (SCs) is crucial for understanding mechanisms underlying demyelination and remyelination, which may help gain insights into incurable disorders like neurodegenerative diseases. In this study, a gelatin-based hydrogel, gelatin methacryloyl (GelMA), was optimized to achieve the biocompatibility, porosity, mechanical stability, and degradability needed to provide high cell viability for dorsal root ganglia (DRG) neurons and SCs, and to enable their long-term coculture needed for myelination studies. The results of cell viability, neurite elongation, SC function and maturation, SC-axon interaction, and myelination were compared with two other commonly used substrates, namely collagen and Poly-D Lysine (PDL). The tuned GelMA constructs (Young's modulus of 32.6 +/- 1.9 kPa and the median value of pore size of 10.3 mu m) enhanced single axon generation (unlike collagen) and promoted the interaction of DRG neurons and SCs (unlike PDL). While DRG cells exhibited relatively higher viability on PDL after 48 h, i.e., 83.8%, the cells had similar survival rate on GelMA and collagen substrates, 66.7% and 61.5%, respectively. Further adjusting the hydrogel properties to achieve two distinct ranges of relatively small and large pores supported SCs to extend their processes freely and enabled physical contact with and wrapping around their corresponding axons. Staining the cells with myelin basic protein (MBA) and myelin-associated glycoprotein (MAG) revealed enhanced myelination on GelMA hydrogel compared to PDL and collagen. Moreover, the engineered porosity enhanced DRGs and SCs attachments and flexibility of movement across the substrate. This engineered hydrogel structure can now be further explored to model demyelination in neurodegenerative diseases, as well as to study the effects of various compounds on myelin regeneration.
机译：调查Schwann细胞（SCS）的轴突髓鞘，对理解脱髓鞘和重新激化的理解机制至关重要，这可能有助于深入了解神经变性疾病等可治区的洞察力。在本研究中，优化了一种基于明胶基水凝胶，以实现生物相容性，孔隙率，机械稳定性和可降解性，以为背根神经节（DRG）神经元和SCS提供高细胞活力所需的可降解性，并实现他们的长期共科治疗髓鞘研究。将细胞活力，神经凝胶伸长，SC功能和成熟，SC-Axon相互作用和髓鞘的结果与另外两个常用的基材进行比较，即胶原蛋白和聚-D赖氨酸（PDL）。调谐的凝胶构建体（杨氏模量为32.6 +/- 1.9 KPA，孔径为10.3μm的中位数）增强了单一轴突发电（与胶原蛋白不同）并促进DRG神经元和SCS的相互作用（与PDL不同）。虽然DRG细胞在48小时后在PDL上表现出相对较高的活力，即83.8％，细胞在凝胶和胶原蛋白基质上具有相似的存活率，分别为66.7％和61.5％。进一步调节水凝胶特性以实现两个不同范围的相对小和大的孔，支撑SCs以自由地延伸它们的工艺，并使它们的处理能够与其相应的轴突一起缠绕和包裹。用髓鞘碱性蛋白（MBA）和髓鞘相关糖蛋白（MAG）染色细胞，与PDL和胶原蛋白相比，在GELMA水凝胶上显示出增强的髓鞘。此外，工程化孔隙率增强了DRG和SCS附着和衬底上的运动的柔韧性。现在可以进一步探索这种工程化水凝胶结构以模拟神经变性疾病的脱髓鞘，以及研究各种化合物对髓鞘再生的影响。

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  • 来源
    《Materials science & engineering》 |2021年第7期|112131.1-112131.12|共12页
  • 作者

    Shahidi Sahar; Janmaleki Mohsen; Riaz Saba; Nezhad Amir Sanati; Syed Naweed;

  • 作者单位

    Univ Calgary Hotchkiss Brain Inst Calgary AB T2N 1N4 Canada|Univ Calgary Res Inst Alberta Childrens Hosp Calgary AB T2N 1N4 Canada;

    Univ Calgary Biomed Engn Grad Program BioMEMS & Bioinspired Microfluid Lab Calgary AB T2N 1N4 Canada|Univ Calgary Ctr BioEngn Res & Educ Calgary AB T2N 1N4 Canada;

    Univ Calgary Hotchkiss Brain Inst Calgary AB T2N 1N4 Canada|Univ Calgary Res Inst Alberta Childrens Hosp Calgary AB T2N 1N4 Canada;

    Univ Calgary Biomed Engn Grad Program BioMEMS & Bioinspired Microfluid Lab Calgary AB T2N 1N4 Canada|Univ Calgary Ctr BioEngn Res & Educ Calgary AB T2N 1N4 Canada;

    Univ Calgary Hotchkiss Brain Inst Calgary AB T2N 1N4 Canada|Univ Calgary Res Inst Alberta Childrens Hosp Calgary AB T2N 1N4 Canada;

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  • 正文语种 eng
  • 中图分类
  • 关键词

    Myelination; Hydrogel; Gelatin methacryloyl; Schwann cells; Dorsal root ganglia neurons; In vitro three-dimensional (3D) tissues;

    机译：髓鞘;水凝胶;明胶甲基丙烯酰基;施曼细胞;背根神经节神经元;体外三维（3D）组织;

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