The development of 3D in vitro models capable of recapitulating native tumor microenvironments could improve the translatability of potential anticancer drugs and treatments. Here, 3D bioprinting techniques are used to build tumor constructs via precise placement of living cells, functional biomaterials, and programmable release capsules. This enables the spatiotemporal control of signaling molecular gradients, thereby dynamically modulating cellular behaviors at a local level. Vascularized tumor models are created to mimic key steps of cancer dissemination (invasion, intravasation, and angiogenesis), based on guided migration of tumor cells and endothelial cells in the context of stromal cells and growth factors. The utility of the metastatic models for drug screening is demonstrated by evaluating the anticancer efficacy of immunotoxins. These 3D vascularized tumor tissues provide a proof-of-concept platform to i) fundamentally explore the molecular mechanisms of tumor progression and metastasis, and ii) preclinically identify therapeutic agents and screen anticancer drugs.
Bibliographical noteFunding Information:
The authors thank Michael J. Ehrhardt for performing EGF and VEGF assays in the Cytokine Reference Laboratory (University of Minnesota, CLIA’88 licensed facility: #24D0931212), Daniel C. Sorby from the 3D Bioprinting Facility (University of Minnesota) for providing printing consumables, and Dr. Jakub Tolar for providing fibroblasts. F.M. was partially supported by a Cancer Bioengineering Fellowship from the Physical Sciences in Oncology Center (PSOC) at the University of Minnesota. The study was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Award No. 1R21EB022830) awarded to A.P.-M., a seed grant from the UMN Institute for Engineering in Medicine, and a Pilot Project award from the UMN Prostate and Urologic Cancer Translational Workgroup. M.C.M. acknowledges the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Award No. 1DP2EB020537). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- 3D printing
- cell migration
- drug screening
- metastatic cancer model
- tumor microenvironment
PubMed: MeSH publication types
- Journal Article
Supporting data for "3D Bioprinted In Vitro Metastatic Models via Reconstruction of Tumor Microenvironments"