Department of Bioengineering, McGill University, Montreal, Quebec, Canada.
Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada.
Biofabrication. 2021 Mar 10;13(2). doi: 10.1088/1758-5090/abdb87.
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 recapitulatepatient 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.
由受控比例的藻酸盐、明胶和基质胶组成的水凝胶使开发患者来源的生物打印组织模型成为可能，这些模型支持癌症球体的生长和扩增。这些工程模型可以被解离，然后被重新引入到新的水凝胶溶液中，并随后被重新打印以生成多代模型。通过螯合交联藻酸盐的离子，可以从 3D 生物打印模型中收获细胞，导致凝胶变弱。将明胶和基质胶部分纳入水凝胶可以通过提供细胞基质结合位点并促进癌细胞与其微环境之间的串扰来提高生物活性。在这里，我们表明，永生化的三阴性乳腺癌细胞（MDA-MB-231）和患者来源的胃腺癌细胞可以在藻酸盐/明胶/基质胶水凝胶中进行生物打印后，至少进行三个 21 天的培养循环再打印。我们的药物测试结果表明，我们的 3D 生物打印模型也可用于重现患者的药物反应。此外，我们的结果表明，迭代生物打印技术与藻酸盐生物材料结合可以用于在不损害细胞活力、改变分裂率或破坏癌症球体形成的情况下，延长时间维持和扩展患者来源的癌症球体培养。
