Thermoresponsive poly(N-isopropylacrylamide) hydrogel substrates micropatterned with poly(ethylene glycol) hydrogel for adipose mesenchymal stem cell spheroid formation and retrieval

Kim, Gyeongju; Jung, Yuna; Cho, Kanghee; Lee, Hyun Jong; Koh, Won Gun

doi:10.1016/j.msec.2020.111128

Cited by 16 publications

(10 citation statements)

References 45 publications

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“…The results show that our microfluidic device is capable of generating a large number of tumor spheroids with uniform size distribution where distinct growth patterns can be observed and quantitatively calculated at statistically significant numbers. Similar microfluidic spheroid cultures used to grow mesenchymal cell lines have shown to form significantly different spheroid sizes per culture chamber, with decline in growth of cells within the first 5 days [68]. Commercial devices (e.g.…”

Section: Formation and Growth Of Cell Spheroidsmentioning

confidence: 99%

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

2020

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Vascular endothelial growth factor (VEGF) is a major cytokine in tumor biology affecting tumor survival, aggressiveness and pro-angiogenetic activities. In addition, cellular stresses often result in aggressive pro-angiogenetic behavior in tumors. For in vitro study, conventional monolayer cell culture has been broadly exploited; however, it often provides limited information due to its different microenvironment from that in vivo. Recently, three-dimensional (3D) cell spheroid culture provides in vivo-like microenvironments to study tumor biology and their survival mechanisms with better predictive power. In this work, vascular endothelial growth factor of type A (VEGF-A) secretion from osteosarcoma (MG-63) cells cultured using monolayer and 3D spheroid models under two stress conditions: nutrient deficiency (reduced serum culture) and hypoxia-inducible factor (HIF) inhibition (HIF inhibitor, YC-1) are characterized and systematically compared. In order to obtain ample sample size for consistent characterization of cellular responses from cancer spheroids under the stresses and compare the responses to those from the conventional monolayer model, a microfluidic spheroid formation and culture device is utilized in the experiments. In the analysis, cell viability is estimated from captured images, and quantification of VEGF-A secreted from the cells is achieved using enzyme-linked immunosorbent assay (ELISA). The experimental results show that the viabilities decrease when the cells face higher stress levels in both monolayer and 3D spheroid culture models; however, the VEGF-A secretion profiles between the cell culture models are different. The VEGF-A secretion decreases when the cells face higher stress conditions in the monolayer cell culture. In contrast, for the 3D spheroid culture, the VEGF-A concentration decreases for low stress levels but increases while the stress level is high. The VEGF-A regulation in the 3D models mimics in vivo cases of tumor survival and can provide insightful information to investigate tumor angiogenesis in vitro. The approach developed in this paper provides an efficient method to quantitatively and statistically study tumor growth kinetics and stress responses from highly uniform samples and it can also be applied to compare the underlying biomolecular mechanisms in monolayer and 3D spheroid culture models to elucidate the effects of microenvironments on cellular response in cancer research.

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Section: Formation and Growth Of Cell Spheroidsmentioning

confidence: 99%

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

2020

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“…Part of the reasons could be attributed to the study design of the surface patterning studies, as most of the studies compared the patterned and unpatterned surfaces fabricated by the same technology, 45,56 or chemical modification would also be performed on the patterned hydrogel. 57,58 …”

Section: Techniques To Fabricate Patterned Hydrogelsmentioning

confidence: 99%

The effects of surface topography modification on hydrogel properties

2021

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Hydrogel has been an attractive biomaterial for tissue engineering, drug delivery, wound healing, and contact lens materials, due to its outstanding properties, including high water content, transparency, biocompatibility, tissue mechanical matching, and low toxicity. As hydrogel commonly possesses high surface hydrophilicity, chemical modifications have been applied to achieve the optimal surface properties to improve the performance of hydrogels for specific applications. Ideally, the effects of surface modifications would be stable, and the modification would not affect the inherent hydrogel properties. In recent years, a new type of surface modification has been discovered to be able to alter hydrogel properties by physically patterning the hydrogel surfaces with topographies. Such physical patterning methods can also affect hydrogel surface chemical properties, such as protein adsorption, microbial adhesion, and cell response. This review will first summarize the works on developing hydrogel surface patterning methods. The influence of surface topography on interfacial energy and the subsequent effects on protein adsorption, microbial, and cell interactions with patterned hydrogel, with specific examples in biomedical applications, will be discussed. Finally, current problems and future challenges on topographical modification of hydrogels will also be discussed.

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“…The most common method of substrate modification to obtain low‐adherence substrate is through material coating. A wide range of materials have been used for this purpose, including agarose (Abe‐Fukasawa et al, 2018; Tevis et al, 2017), poly(2‐hydroxyethyl methacrylate) (poly‐HEMA; M. Kim et al, 2018), poly(ethylene glycol) (PEG; Tong et al, 2016), galactose (Tong et al, 2016), polyvinyl alcohol (PVA; Huang et al, 2013) and poly( N ‐isopropylacrylamide) (PNIPAAm; G. Kim et al, 2020). Other than material coating, substrate adherence can also be modified with topological nano‐/micro‐scale features (S.‐J.…”

Section: Current Mainstream Technologies For Cell Spheroid Generationmentioning

confidence: 99%

“…Low‐adherence substrates support the generation of cell spheroids in large quantities with minimal liquid handling requirement. However, it does not have good control over the spheroid size (Y. Wang et al, 2016), unless the substrates are patterned into small regions to produce one spheroid per region (G. Kim et al, 2020). Alternatively, low‐adherence substrate can be combined with microwells (to be introduced in the next section) to produce spheroids of repeatable and consistent quality.…”

Section: Current Mainstream Technologies For Cell Spheroid Generationmentioning

confidence: 99%

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A review of manufacturing capabilities of cell spheroid generation technologies and future development

Liú

Chen

Naing

2020

Biotech & Bioengineering

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Spheroid culture provides cells with a three‐dimensional environment that can better mimic physiological conditions compared to monolayer culture. Technologies involved in the generation of cell spheroids are continuously being innovated to produce spheroids with enhanced properties. In this paper, we review the manufacturing capabilities of current cell spheroid generation technologies. We propose that spheroid generation technologies should enable tight and robust process controls to produce spheroids of consistent and repeatable quality. Future technology development for the generation of cell spheroids should look into improvement in process control, standardization, scalability and monitoring, in addition to advanced methods of spheroid transfer and characterization.

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Thermoresponsive poly(N-isopropylacrylamide) hydrogel substrates micropatterned with poly(ethylene glycol) hydrogel for adipose mesenchymal stem cell spheroid formation and retrieval

Cited by 16 publications

References 45 publications

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

Comparison of VEGF-A secretion from tumor cells under cellular stresses in conventional monolayer culture and microfluidic three-dimensional spheroid models

The effects of surface topography modification on hydrogel properties

A review of manufacturing capabilities of cell spheroid generation technologies and future development

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