Modular microporous hydrogels formed from microgel beads with orthogonal thermo-chemical responsivity: Microfluidic fabrication and characterization

Amir Sheikhi; Joseph de Rutte; Reihaneh Haghniaz; Outman Akouissi; Alireza Sohrabi; Dino Di Carlo; Ali Khademhosseini

MethodsX (Jan 2019)

Modular microporous hydrogels formed from microgel beads with orthogonal thermo-chemical responsivity: Microfluidic fabrication and characterization

Amir Sheikhi,
Joseph de Rutte,
Reihaneh Haghniaz,
Outman Akouissi,
Alireza Sohrabi,
Dino Di Carlo,
Ali Khademhosseini

Affiliations

Amir Sheikhi: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA; Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA; California NanoSystems Institute (CNSI), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA; Corresponding authors at: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA.
Joseph de Rutte: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA
Reihaneh Haghniaz: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA; Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA; California NanoSystems Institute (CNSI), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA
Outman Akouissi: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA; Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA; California NanoSystems Institute (CNSI), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA
Alireza Sohrabi: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA
Dino Di Carlo: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA; California NanoSystems Institute (CNSI), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90024, USA; Corresponding authors at: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA.
Ali Khademhosseini: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA; Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA; California NanoSystems Institute (CNSI), University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90024, USA; Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, Los Angeles, CA 90095, USA; Corresponding authors at: Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, Los Angeles, CA 90095, USA.

Journal volume & issue: Vol. 6
pp. 1747 – 1752

Abstract

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Despite the significant advances in designing injectable bulk hydrogels, the inability to control the pore interconnectivity and decoupling it from the matrix stiffness has tremendously limited the applicability of stiff, flowable hydrogels for 3D cellular engineering, e.g., in hard tissue engineering. To overcome this persistent challenge, here, we introduce a universal method to convert thermosensitive macromolecules with chemically-crosslinkable moieties into annealable building blocks, forming 3D microporous beaded scaffolds in a bottom-up approach. In particular, we show gelatin methacryloyl (GelMA), a widely used biomaterial in tissue engineering, may be converted into physically-crosslinked microbeads using a facile microfluidic approach, followed by flow of the microbead suspension and chemical crosslinking in situ to fabricate microporous beaded GelMA (B-GelMA) scaffolds with interconnected pores, promoting cell functionality and rapid (within minutes) 3D seeding in stiff scaffolds, which are otherwise impossible in the bulk gel counterparts. This novel approach may set the stage for the next generation modular hydrogels with orthogonal porosity and stiffness made up of a broad range of natural and synthetic biomaterials. • This method combines well-known flow focusing microfluidic devices with facile post-processing steps to fabricate microporous scaffolds. • Temperature-driven physical crosslinking of the microbeads enables the facile purification of gel building blocks without further chemical reactions. • This method provides a simple approach to fabricate microporous scaffolds, which overcomes some of the challenges of newly emerging beaded scaffolds, including oxygen-mediated impaired crosslinking. Method name: Microfluidic thermo-chemical fabrication of hydrogel beads for microporous scaffold assembly, Keywords: Modular hydrogels, Microporous scaffolds, Microbeads, Particle gels, Tissue engineering, 3D cell seeding, Gelatin methacryloyl, GelMA

Published in MethodsX

ISSN: 2215-0161 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science
Website: http://www.journals.elsevier.com/methodsx/

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