Poster AA20 - A Versatile 3D Bioprinted Vascularized In-vitro Tissue Model: Non-Small Cell Lung Cancer Assay Platform for Drug Discovery and Development

Introduction: Three dimensional (3D) bioprinting technologies are enabling the development of physiologically relevant in vitro assay platforms that mimic native tissue-like structures, and its repeatability and reproducibility allows for high throughput screening (HTS) assays. It is now possible to reliably bioprint 3D tissue models in a multiwell plate format and develop robust tissue-like cellular assays for drug screening. We have previously established a protocol to bioprint vascularized tissue constructs in a 96 well format to form microvessels with a patent lumen and with strong angiogenic activity. The vasculature is a key component of the TME and the interactions between vasculature and cancer cells play a key role in cancer growth and metastasis. However, most of the assays used for cancer drug discovery and development lack the TME component and therefore do not capture the cancer-TME interactions. We have demonstrated that the bioprinting protocols to make a vascularized tissue can be used to create a robust assay for cancer cell growth on a vascularized tumor microenvironment (TME). Our established protocol features a modular approach that maximizes versatility to introduce different cancer cell types and increase TME tissue physiological complexity for increase clinical predictability.

Materials and

Methods: Here we demonstrate the application of the protocols to make vascularized cancer models to bioprint 96-well HTS-amenable in vitro 3D model of vascularized lung cancer. We used GFP expressing human primary lung vascular endothelial cells, placental pericytes and lung fibroblast cells embedded in a fibrin-gelatin hydrogel. Then, three lung RFP expressing cancer cell lines, A549, H1975, or H460, were embedded in a fibrin gel covers the printed vasculature. We used live cell image-based computational analysis to enable quantitation of vasculature integrity and tumor growth.

Results, Conclusions, and Discussions: Using these models, we were able to distinguish different growth modes and tumor-vessel interactions depending on the cancer cell line. We also compared the tumor growth in avascular bioprinted lung model and observed that the presence of vasculature significantly induced H1975 and A549 cell migration patterns. The model will be applied for the HTS of 613 chemotherapeutic compounds. We believe that this will be the first step to demonstrate the usefulness of the bioprinted tissue models toward discovery of better anti-cancer drugs.

Acknowledgements (Optional): This research was supported in part by the Intramural/Extramural research program of the NCATS, NIH