Oxygen-Purged Microfluidic Device to Enhance Cell Viability in Photopolymerized PEG Hydrogel Microparticles

Xia, Bingzhao; Krutkramelis, Kaspars; Oakey, John

doi:10.1021/acs.biomac.6b00597

Cited by 36 publications

(60 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three approaches have been widely used for this purpose: photo crosslinking, chemical agents, and thermal assembly. Many polymers, such as dextran hydroxyethyl methacrylate 103 , polyethylene glycol diacrylate 104 , collagen-gelatin 105 , and ethocylated trimethylolpropane triacrylate 106 , can be readily crosslinked into hydrogel matrix by ultra-violet (UV) or blue light, because most current microfluidic devices are made of optically clear polydimethylsiloxane (PDMS) or glass. Particularly, both collagen and gelatin hydrogel particles can be obtained and strengthened by irreversible riboflavin-mediated crosslinking under blue light irradiation 105, 107 .…”

Section: Generation Of Cell-laden Hydrogel Microcapsulesmentioning

confidence: 99%

Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture

et al. 2017

View full text Add to dashboard Cite

Hydrogel microcapsules provide miniaturized and biocompatible niches for three-dimensional (3D) in vitro cell culture. They can be easily generated by droplet-based microfluidics with tunable size, morphology, and biochemical properties. Therefore, microfluidic generation and manipulation of cell-laden microcapsules can be used for 3D cell culture to mimic the in vivo environment towards applications in tissue engineering and high throughput drug screening. In this review of recent advances mainly since 2010, we will first introduce general characteristics of droplet-based microfluidic devices for cell encapsulation with an emphasis on the fluid dynamics of droplet breakup and internal mixing as they directly influence microcapsule’s size and structure. We will then discuss two on-chip manipulation strategies: sorting and extraction from oil into aqueous phase, which can be integrated into droplet-based microfluidics and significantly improve the qualities of cell-laden hydrogel microcapsules. Finally, we will review various applications of hydrogel microencapsulation for 3D in vitro culture on cell growth and proliferation, stem cell differentiation, tissue development, and co-culture of different types of cells.

show abstract

Section: Generation Of Cell-laden Hydrogel Microcapsulesmentioning

confidence: 99%

Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture

et al. 2017

View full text Add to dashboard Cite

show abstract

“…PEGDA has been widely proven as a viable material for cell encapsulation, and has recently been shown to support high cell viability immediately following encapsulation and photopolymerization in microdroplets 39 . To evaluate the biocompatibility of PEGNB as a cell encapsulant relative to PEGDA under different encapsulation conditions, A549s were encapsulated into PEGNB or PEGDA bulk hydrogels and hydrogel microspheres.…”

Section: Resultsmentioning

confidence: 99%

“…38 This device, a nitrogen-jacketed double layer device (Fig. 5C) was introduced to circumvent oxygen inhibition of PEGDA 39 by eliminating oxygen diffusion to the droplet from the PDMS device or oil. Immediately after encapsulation, high cell viability was achieved in both blank PEGNB and RGDS-modified PEGDA hydrogel microspheres.…”

Section: Resultsmentioning

confidence: 99%

“…For PEGNB droplet formation, channel dimensions (h × w) were 80 μm × 100 μm for the cell-containing aqueous phase and 80 μm × 30 μm for the oil phase. Double layer nitrogen-jacketed microfluidic devices for PEGDA particle production were fabricated as previously described 39 .…”

Section: Methodsmentioning

confidence: 99%

“…Sustained cell viability following photoencapsulation is a critical parameter for therapeutic cell delivery applications. However, even though high initial post-encapsulation cell viability can be achieved after encapsulating cells within PEGDA hydrogel microspheres 38,39 , a dramatic decrease in cell viability is typically observed over longer time periods 45 . Thus, an integrated solution that combines technology with materials chemistry is needed to successfully encapsulate live cells and maintain their high cell viability in microgels for weeks, in order to conduct long-term studies.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres

et al. 2017

Self Cite

View full text Add to dashboard Cite

Cell encapsulation within photopolymerized polyethylene glycol (PEG)-based hydrogel scaffolds has been demonstrated as a robust strategy for cell delivery, tissue engineering, regenerative medicine, and developing in vitro platforms to study cellular behavior and fate. Strategies to achieve spatial and temporal control over PEG hydrogel mechanical properties, chemical functionalization, and cytocompatibility have advanced considerably in recent years. Recent microfluidic technologies have enabled the miniaturization of PEG hydrogels, thus enabling the fabrication of miniaturized cell-laden vehicles. However, rapid oxygen diffusive transport times on the microscale dramatically inhibit chain growth photopolymerization of polyethylene glycol diacrylate (PEGDA), thus decreasing the viability of cells encapsulated within these microstructures. Another promising PEG-based scaffold material, PEG norbornene (PEGNB), is formed by a step-growth photopolymerization and is not inhibited by oxygen. PEGNB has also been shown to be more cytocompatible than PEGDA and allows for orthogonal addition reactions. The step-growth kinetics, however, are slow and therefore challenging to fully polymerize within droplets flowing through microfluidic devices. Here, we describe a microfluidic-based droplet fabrication platform that generates consistently monodisperse cell-laden water-in-oil emulsions. Microfluidically generated PEGNB droplets are collected and photopolymerized under UV exposure in bulk emulsions. In this work, we compare this microfluidic-based cell encapsulation platform with a vortex-based method on the basis of microgel size, uniformity, post-encapsulation cell viability and long-term cell viability. Several factors that influence post-encapsulation cell viability were identified. Finally, long-term cell viability achieved by this platform was compared to a similar cell encapsulation platform using PEGDA. We show that this PEGNB microencapsulation platform is capable of generating cell-laden hydrogel microspheres at high rates with well-controlled size distributions and high long-term cell viability.

show abstract

Creating Physicochemical Gradients in Modular Microporous Annealed Particle Hydrogels via a Microfluidic Method

Xin

Dai

Gregory

et al. 2019

Adv Funct Materials

View full text Add to dashboard Cite

Microporous annealed particle (MAP) hydrogels are an attractive platform for engineering biomaterials with controlled heterogeneity. Here, a microfluidic method is introduced to create physicochemical gradients within poly(ethylene glycol) based MAP hydrogels. By combining microfluidic mixing and droplet generator modules, microgels with varying properties are produced by adjusting the relative flow rates between two precursor solutions and collected layer-by-layer in a syringe. Subsequently, the microgels are injected out of the syringe and then annealed with thiol-ene click chemistry. Fluorescence intensity measurements of constructs annealed in vitro and after mock implantation into a tissue defect show that a continuous gradient profile is achieved and maintained after injection, indicating utility for in situ hydrogel formation. The effects of physicochemical property gradients on human mesenchymal stem cells (hMSCs) are also studied. Microgel stiffness is studied first, and the hMSCs exhibit increased spreading and proliferation as stiffness increased along the gradient. Microgel degradability is also studied, revealing a critical degradability threshold above which the hMSCs spread robustly and below which they are isolated and exhibit reduced spreading. This method of generating spatial gradients in MAP hydrogels can be further used to gain new insights into cell-material interactions, which can be leveraged for tissue engineering applications.

show abstract

Oxygen-Purged Microfluidic Device to Enhance Cell Viability in Photopolymerized PEG Hydrogel Microparticles

Cited by 36 publications

References 65 publications

Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture

Generation and manipulation of hydrogel microcapsules by droplet-based microfluidics for mammalian cell culture

A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres

Creating Physicochemical Gradients in Modular Microporous Annealed Particle Hydrogels via a Microfluidic Method

Contact Info

Product

Resources

About