Promoting 3D neuronal differentiation in hydrogel for spinal cord regeneration

Zhou, Pinghui; Xu, Panpan; Guan, Jingjing; Zhang, Changchun; Chang, Jianrong; Yang, Fugen; Xiao, Hui; Sun, Hanxiao; Zhang, Zhuoran; Wang, Mengqing; Hu, Jianguo; Mao, Yingji

doi:10.1016/j.colsurfb.2020.111214

Cited by 45 publications

(20 citation statements)

References 33 publications

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“…A study led by Zhou et al used bone mesenchymal stem cells (BMSCs) and NSCs photocrosslinked in various concentrations of GelMA hydrogels to derive oligodendrocytes and neuronal cells for SC regeneration. [ 58 ] These GelMa hydrogels produced significantly more neurons and oligodendrocytes as measured using optical density. Others have used combinations of natural biomaterials to 3D bioprint human NSCs using an alginate/carboxymethyl‐chitosan (CMC)/agarose bioink leading to the increased presence of various mature neuronal cell types such as GABAergic neurons in comparison with 2D and 3D control cultures as indicated by qPCR analysis of neuronal markers.…”

Section: Discussionmentioning

confidence: 99%

3D Bioprinting Human‐Induced Pluripotent Stem Cells and Drug‐Releasing Microspheres to Produce Responsive Neural Tissues

Vega

Abelseth

Sharma

et al. 2021

Advanced NanoBiomed Research

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3D bioprinting can produce complex human tissue mimics using stem cells (SCs). Herein, cylindrical constructs containing human‐induced pluripotent stem cell (hiPSC)‐derived neural progenitor cells (NPCs) encapsulated in a fibrin‐based bioink containing polycaprolactone (PCL)–retinoic acid (RA) and purmorphamine (puro)‐releasing microspheres are bioprinted in a layer‐by‐layer fashion using the microfluidic‐based RX1 bioprinter to engineer responsive neural tissues. The differentiated constructs contain neurons expressing ChAT, GABA, and MAP2, astrocytes expressing GFAP, and oligodendrocytes expressing O4 as indicated by immunocytochemistry and flow cytometry analysis on days 30 and 45. The bioprinted tissues also respond to treatment with acetylcholine (Ach) and gamma‐aminobutyric acid (GABA) on days 30 and 45. The use of microsphere‐laden bioinks efficiently promotes neural tissue differentiation and maturation in situ using a lower amount of morphogens in comparison with using soluble drugs. This bioprinting strategy serves as a cost‐effective solution for engineering humanized neural tissues.

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Section: Discussionmentioning

confidence: 99%

3D Bioprinting Human‐Induced Pluripotent Stem Cells and Drug‐Releasing Microspheres to Produce Responsive Neural Tissues

Vega

Abelseth

Sharma

et al. 2021

Advanced NanoBiomed Research

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“…Additionally, alginate was oxidized with sodium periodate in order to create a more readily degradable shell that would allow for control of the mechanical integrity and permeability of the microcapsule shell to study their impact on the growth and early neural differentiation of ESCs. In addition, other hydrogel materials including fibrin, collagen, and gelatin methacryloyl previously used as the scaffold for stem cell differentiation [Sheykhhasan et al, 2015;Li et al, 2019;Zhou et al, 2020], may be used as the microcapsule core and/or shell materials. Furthermore, the mechanical properties of the 3D culture can be controlled by tuning the composition and degradation of the microcapsule core and/or shell materials with different hydrogels and modifications to regulate the differentiation of stem cells.…”

Section: Discussionmentioning

confidence: 99%

Oxidation and RGD Modification Affect the Early Neural Differentiation of Murine Embryonic Stem Cells Cultured in Core-Shell Alginate Hydrogel Microcapsules

Dumbleton

Shamul

Jiang

et al. 2021

Cells Tissues Organs

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Directed neural differentiation of embryonic stem cells (ESCs) has been studied extensively to improve the treatment of neurodegenerative disorders. This can be done through stromal-cell derived inducing activity (SDIA), by culturing ESCs directly on top of a layer of feeder stromal cells. However, the stem cells usually become mixed with the feeder cells during the differentiation process, making it difficult to obtain a pure population of the differentiated cells for further use. To address this issue, a non-planar microfluidic device is used here to encapsulate murine ESCs (mESCs) in the 3D liquid core of microcapsules with an alginate hydrogel shell of different sizes for early neural differentiation through SDIA, by culturing mESC-laden microcapsules over a feeder layer of PA6 cells. Furthermore, the alginate hydrogel shell of the microcapsules is modified via oxidation or RGD peptide conjugation to examine the mechanical and chemical effects on neural differentiation of the encapsulated mESC aggregates. A higher expression of Nestin is observed in the aggregates encapsulated in small (∼300 μm) microcapsules and cultured over the PA6 cell feeder layer. Furthermore, the modification of the alginate with RGD facilitates early neurite extension within the microcapsules. This study demonstrates that the presence of the RGD peptide, the SDIA effect of the PA6 cells, and the absence of leukemia inhibition factor from the medium can lead to the early differentiation of mESCs with extensive neurites within the 3D microenvironment of the small microcapsules. This is the first study to investigate the effects of cell adhesion and degradation of the encapsulation materials for directed neural differentiation of mESCs. The simple modifications (i.e., oxidation and RGD incorporation) of the miniaturized 3D environment for improved early neural differentiation of mESCs may potentially enhance further downstream differentiation of the mESCs into more specialized neurons for therapeutic use and drug screening.

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“…The mechanical properties of GelMA hydrogels can have a significant effect on cell survival, proliferation, and differentiation 46 . In our previous studies, we changed the mechanical properties of the GelMA hydrogel to affect the differentiation of co‐cultured neural stem cells and bone marrow mesenchymal stem cells 47 . In this study, we prepared GelMA hydrogels at three concentrations, 5%, 10%, and 15%, by adjusting the ratio of methacrylate.…”

Section: Discussionmentioning

confidence: 99%

Stiffness of photocrosslinkable gelatin hydrogel influences nucleus pulposus cell propertiesin vitro

Guan

Chen

et al. 2020

J Cellular Molecular Medi

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Promoting 3D neuronal differentiation in hydrogel for spinal cord regeneration

Cited by 45 publications

References 33 publications

3D Bioprinting Human‐Induced Pluripotent Stem Cells and Drug‐Releasing Microspheres to Produce Responsive Neural Tissues

3D Bioprinting Human‐Induced Pluripotent Stem Cells and Drug‐Releasing Microspheres to Produce Responsive Neural Tissues

Oxidation and RGD Modification Affect the Early Neural Differentiation of Murine Embryonic Stem Cells Cultured in Core-Shell Alginate Hydrogel Microcapsules

Stiffness of photocrosslinkable gelatin hydrogel influences nucleus pulposus cell propertiesin vitro

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