Journal
BIOFABRICATION
Volume 10, Issue 2, Pages -Publisher
IOP PUBLISHING LTD
DOI: 10.1088/1758-5090/aa9d44
Keywords
bioprinting; alginate; gelatin methacryloyl (GelMA); cell-laden; hydrogel; tissue engineering
Funding
- National Institutes of Health [AR057837, DE021468, AR068258, AR066193, EB022403, EB021148]
- Presidential Early Career Award for Scientists and Engineers (PECASE)
- Fundamental Research Funds for the Central Universities from China [14D310106]
- program of China Scholarships Council [201406630041]
- National Cancer Institute of the National Institutes of Health Pathway to Independence Award [K99CA201603]
- NATIONAL CANCER INSTITUTE [K99CA201603] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R21AR068258, R01AR066193, R01AR057837] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R21EB022403, R21EB021148] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE021468] Funding Source: NIH RePORTER
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Bioinks with shear-thinning/rapid solidification properties and strong mechanics are usually needed for the bioprinting of three-dimensional (3D) cell-laden constructs. As such, it remains challenging to generate soft constructs from bioinks at low concentrations that are favorable for cellular activities. Herein, we report a strategy to fabricate cell-laden constructs with tunable 3D microenvironments achieved by bioprinting of gelatin methacryloyl (GelMA)/alginate core/sheath microfibers, where the alginate sheath serves as a template to support and confine the GelMA pre-hydrogel in the core during the extrusion process, allowing for subsequent UV crosslinking. This novel strategy minimizes the bioprinting requirements for the core bioink, and facilitates the fabrication of cell-laden GelMA constructs at low concentrations. We showed the capability of generating various alginate hollow microfibrous constructs using a coaxial nozzle setup, and verified the diffusibility and perfusability of the bioprinted hollow structures which are important for the tissue-engineering applications. More importantly, the hollow alginate microfibers were used as templates for generating cell-laden GelMA constructs with soft microenvironments, by using GelMA pre-hydrogel as the bioink for the core phase during bioprinting. As such, GelMA constructs at extremely low concentrations (down to 1.5%) could be extruded to effectively support cellular activities including proliferation and spreading for various cell types. We believe that our strategy is likely to provide broad opportunities in bioprinting 3D constructs with cell-favorable microenvironments for applications in tissue engineering and pharmaceutical screening.
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