期刊
BIOFABRICATION
卷 13, 期 2, 页码 -出版社
IOP Publishing Ltd
DOI: 10.1088/1758-5090/abdb87
关键词
bioprinting; cell reprinting; cancer spheroids; 3D cancer cell culture; alginate
资金
- National Science and Engineering Research Council [NSERC RGPIN- 06671-14]
- Canadian Foundation for Innovation
- Townshend-Lamarre Family Foundation at the Goodman Cancer Research Centre at McGill University
- McGill University
- Cancer Research Society
- Canadian Institute of Health Research Foundation
- CONACYT-I2T2 [751540, 754427]
- McGill Engineering Doctoral Award [90025]
- FRQNT [258421, 288490, 291010]
- CONACYT [291168, 291258]
- MITACS [58362]
- China Scholarship Council [201403170354]
This study demonstrates the development of patient-derived bioprinted tissue models using controlled fractions of alginate, gelatin, and Matrigel, supporting cancer spheroid growth. These engineered models can be dissociated and reprinted to generate multigenerational models, showing potential for studying patient drug response in vivo.
Hydrogels consisting of controlled fractions of alginate, gelatin, and Matrigel enable the development of patient-derived bioprinted tissue models that support cancer spheroid growth and expansion. These engineered models can be dissociated to be then reintroduced to new hydrogel solutions and subsequently reprinted to generate multigenerational models. The process of harvesting cells from 3D bioprinted models is possible by chelating the ions that crosslink alginate, causing the gel to weaken. Inclusion of the gelatin and Matrigel fractions to the hydrogel increases the bioactivity by providing cell-matrix binding sites and promoting cross-talk between cancer cells and their microenvironment. Here we show that immortalized triple-negative breast cancer cells (MDA-MB-231) and patient-derived gastric adenocarcinoma cells can be reprinted for at least three 21 d culture cycles following bioprinting in the alginate/gelatin/Matrigel hydrogels. Our drug testing results suggest that our 3D bioprinted model can also be used to recapitulate in vivo patient drug response. Furthermore, our results show that iterative bioprinting techniques coupled with alginate biomaterials can be used to maintain and expand patient-derived cancer spheroid cultures for extended periods without compromising cell viability, altering division rates, or disrupting cancer spheroid formation.
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