An integrated microfluidic flow-focusing platform for on-chip fabrication and filtration of cell-laden microgels

Mohamed, Mohamed G. A.; Kheiri, Sina; Islam, Md. Saidul; Kumar, Hitendra; Yang, Annie; Kim, Keekyoung

doi:10.1039/c9lc00073a

Cited by 51 publications

(34 citation statements)

References 40 publications

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“…[22][23][24] Droplet microfluidics technology is a promising approach for fabricating hydrogel microbeads with well-controlled sizes (low polydispersity) and shapes (sphericity~1). 8,13,20,25,26 We have recently developed a high-throughput, two-step method for the stabilization and annealing of GelMA microbeads to fabricate microporous 3D hydrogel scaffolds in situ. 8,20,27 In this strategy, we use the temperature-induced physical crosslinking of GelMA microbeads, produced as a water-in-oil emulsion using droplet microfluidics, followed by the chemical crosslinking and annealing of beads via free radical photo-annealing.…”

Section: Introductionmentioning

confidence: 99%

“…Droplet microfluidics technology is a promising approach for fabricating hydrogel microbeads with well‐controlled sizes (low polydispersity) and shapes (sphericity ~1) 8,13,20,25,26 . We have recently developed a high‐throughput, two‐step method for the stabilization and annealing of GelMA microbeads to fabricate microporous 3D hydrogel scaffolds in situ 8,20,27 .…”

Section: Introductionmentioning

confidence: 99%

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In situ forming microporous gelatin methacryloyl hydrogel scaffolds from thermostable microgels for tissue engineering

Zoratto

Lisa

Rutte

et al. 2020

Bioengineering & Transla Med

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Converting biopolymers to extracellular matrix (ECM)-mimetic hydrogel-based scaffolds has provided invaluable opportunities to design in vitro models of tissues/diseases and develop regenerative therapies for damaged tissues. Among biopolymers, gelatin and its crosslinkable derivatives, such as gelatin methacryloyl (GelMA), have gained significant importance for biomedical applications due to their ECM-mimetic properties. Recently, we have developed the first class of in situ forming GelMA microporous hydrogels based on the chemical annealing of physically crosslinked GelMA microscale beads (microgels), which addressed several key shortcomings of bulk (nanoporous) GelMA scaffolds, including lack of interconnected micron-sized pores to support on-demand three-dimensional-cell seeding and cell-cell interactions. Here, we address one of the limitations of in situ forming microporous GelMA hydrogels, that is, the thermal instability (melting) of their physically crosslinked building blocks at physiological temperature, resulting in compromised microporosity. To overcome this challenge, we developed a two-step fabrication strategy in which thermostable GelMA microbeads were produced via semi-photocrosslinking, followed by photo-annealing to form stable microporous scaffolds. We show that the semi

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In situ forming microporous gelatin methacryloyl hydrogel scaffolds from thermostable microgels for tissue engineering

Zoratto

Lisa

Rutte

et al. 2020

Bioengineering & Transla Med

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“…[ 60,201–203 ] Multiple fabrication strategies for uniform, high‐throughput generation of these modular hydrogel constructs (microspheres, particles, microfibers and others) via microfluidic technologies have also been developed. [ 48,76,204 ]…”

Section: Fabrication Strategies To Generate Microfluidic and Vascularmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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Section: Introductionmentioning

confidence: 99%

“…[27] GelMA is one of the most extensively used biomaterials for biofabrication applications due to its high biocompatibility, allowing for cell adhesion and proliferation, biodegradability, photocrosslinkability, relative ease of synthesis, and cost-effectiveness. [15,28] GelMA hydrogels have been used as bioinks for LIFT bioprinting, [29] extrusion-based bioprinting, [30] and DLP-SLA bioprinting. [11,31] GelMA synthesis includes several parameters such as the gelatin source, the solvent used as the reaction medium, the pH of the reaction, the methacrylate group donor, the catalyst, and the duration of the reaction.…”

Section: Introductionmentioning

confidence: 99%

Designing Gelatin Methacryloyl (GelMA)‐Based Bioinks for Visible Light Stereolithographic 3D Biofabrication

Kumar

Sakthivel

Mohamed

et al. 2020

Macromolecular Bioscience

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Bioinks play a key role in determining the capability of the biofabricatoin processes and the resolution of the printed constructs. Excellent biocompatibility, tunable physical properties, and ease of chemical or biological modifications of gelatin methacryloyl (GelMA) have made it an attractive choice as bioinks for biomanufacturing of various tissues or organs. However, the current preparation methods for GelMA‐based bioinks lack the ability to tailor their physical properties for desired bioprinting methods. Inherently, GelMA prepolymer solution exhibits a fast sol–gel transition at room temperature, which is a hurdle for its use in stereolithography (SLA) bioprinting. Here, synthesis parameters are optimized such as solvents, pH, and reaction time to develop GelMA bioinks which have a slow sol–gel transition at room temperature and visible light crosslinkable functions. A total of eight GelMA combinations are identified as suitable for digital light processing (DLP)‐based SLA (DLP‐SLA) bioprinting through systematic characterizations of their physical and rheological properties. Out of various types of GelMA, those synthesized in reverse osmosis (RO) purified water (referred to as RO‐GelMA) are regarded as most suitable to achieve high DLP‐SLA printing resolution. RO‐GelMA‐based bioinks are also found to be biocompatible showing high survival rates of encapsulated cells in the photocrosslinked gels. Additionally, the astrocytes and fibroblasts are observed to grow and integrate well within the bioprinted constructs. The bioink's superior physical and photocrosslinking properties offer pathways of tuning the scaffold microenvironment and highlight the applicability of developed GelMA bioinks in various tissue engineering and regenerative medicine applications.

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An integrated microfluidic flow-focusing platform for on-chip fabrication and filtration of cell-laden microgels

Abstract: An integrated microfluidic flow-focusing platform for on-chip fabrication and filtration of cell-laden microgels.

Cited by 51 publications

References 40 publications

In situ forming microporous gelatin methacryloyl hydrogel scaffolds from thermostable microgels for tissue engineering

In situ forming microporous gelatin methacryloyl hydrogel scaffolds from thermostable microgels for tissue engineering

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Designing Gelatin Methacryloyl (GelMA)‐Based Bioinks for Visible Light Stereolithographic 3D Biofabrication

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