Journal
METHODSX
Volume 6, Issue -, Pages 1747-1752Publisher
ELSEVIER
DOI: 10.1016/j.mex.2019.07.018
Keywords
Modular hydrogels; Microporous scaffolds; Microbeads; Particle gels; Tissue engineering; 3D cell seeding; Gelatin methacryloyl; GelMA
Categories
Funding
- Canadian Institutes of Health Research (CIHR)
- National Institutes of Health [HL137193, 5R01AR057837, 1R01EB021857]
- Presidential Early Career Award for Scientists and Engineers [N00014-16-1-2997]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL137193] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR057837] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB021857] Funding Source: NIH RePORTER
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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, maybe 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. (C) 2019 The Authors. Published by Elsevier B.V.
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