Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 18, Pages 20295-20306Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c05096
Keywords
3D bioprinting; oxidized alginate; carbohydrazide-modified gelatin; granular slurry; extrusion-based bioprinting
Funding
- National Science Foundation [1462232]
- Osteology Foundation [15-042]
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MSIT) [NRF-2019M3E5D1A01069356]
- International Postdoctoral Research Scholarship Program (BIDEP 2219) of the Scientific and Technological Research Council of Turkey (TUBITAK)
- National Research Foundation of Korea [2019M3E5D1A01069356] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Directorate For Engineering
- Div Of Civil, Mechanical, & Manufact Inn [1462232] Funding Source: National Science Foundation
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Extrusion-based bioprinting of hydrogels in a granular secondary gel enables the fabrication of cell-laden three-dimensional (3D) constructs in an anatomically accurate manner, which is challenging using conventional extrusion-based bioprinting processes. In this study, carbohydrazide-modified gelatin (Gel-CDH) was synthesized and deposited into a new multifunctional support bath consisting of gelatin microparticles suspended in an oxidized alginate (OAlg) solution. During extrusion, Gel-CDH and OAlg were rapidly cross-linked because of the Schiff base formation between aldehyde groups of OAlg and amino groups of Gel-CDH, which has not been demonstrated in the domain of 3D bioprinting before. Rheological results indicated that hydrogels with lower OAlg to Gel-CDH ratios possessed superior mechanical rigidity. Different 3D geometrically intricate constructs were successfully created upon the determination of optimal bioprinting parameters. Human mesenchymal stem cells and human umbilical vein endothelial cells were also bioprinted at physiologically relevant cell densities. The presented study has offered a novel strategy for bioprinting of natural polymer-based hydrogels into 3D complex-shaped biomimetic constructs, which eliminated the need for cytotoxic supplements as external cross-linkers or additional cross-linking processes, therefore expanding the availability of bioinks.
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