Laser-based 3D bioprinting for spatial and size control of tumor spheroids and embryoid bodies

基于激光的 3D 生物打印用于控制肿瘤球体和胚状体的空间和尺寸

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作者:David M Kingsley, Cassandra L Roberge, Alena Rudkouskaya, Denzel E Faulkner, Margarida Barroso, Xavier Intes, David T Corr

Significance

Multicellular 3D aggregates are powerful in vitro models used to study a wide variety of complex biological processes, particularly within oncology and regenerative medicine. These tissue surrogates are fabricated using environments that encourage cellular self-assembly. However, specific applications require control of aggregate size and position to recapitulate key in vivo parameters (e.g., pathophysiological gradients and homotypic/heterotypic cell signaling). Herein, we demonstrate the ability to create and spatially pattern size-controlled embryoid bodies and tumor spheroids, using laser-based 3D bioprinting. Furthermore, we investigated the effect of tumor spheroid size on internalization of Transferrin, a common ligand for targeted therapy, finding greater spatial heterogeneity in our large aggregates. Overall, this technique offers incredible promise and flexibility for fabricating idealized 3D in vitro models.

Statement of significance

Multicellular 3D aggregates are powerful in vitro models used to study a wide variety of complex biological processes, particularly within oncology and regenerative medicine. These tissue surrogates are fabricated using environments that encourage cellular self-assembly. However, specific applications require control of aggregate size and position to recapitulate key in vivo parameters (e.g., pathophysiological gradients and homotypic/heterotypic cell signaling). Herein, we demonstrate the ability to create and spatially pattern size-controlled embryoid bodies and tumor spheroids, using laser-based 3D bioprinting. Furthermore, we investigated the effect of tumor spheroid size on internalization of Transferrin, a common ligand for targeted therapy, finding greater spatial heterogeneity in our large aggregates. Overall, this technique offers incredible promise and flexibility for fabricating idealized 3D in vitro models.

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