Bioprinted Human Lung Cancer-Mimics for Tissue Diagnostics Applications

Abstract

Developing a reproducible and secure supply of customizable control tissues that standardizes for the cell type, tissue architecture, and preanalytics of interest for usage in applications including diagnostic, prognostic, and predictive assays, is critical for improving our patient care and welfare. The conventionally adopted control tissues directly obtained from patients are not ideal because they oftentimes have different amounts of normal and neoplastic elements, differing cellularity, differing architecture, and unknown preanalytics, in addition to the limited supply availability and thus associated high costs. In this study, we demonstrated a strategy to stably produce tissue-mimics for diagnostics purposes by taking advantage of the three-dimensional (3D) bioprinting technology. Specifically, we take anaplastic lymphoma kinase–positive (Alk+) lung cancer as an example, where a micropore-forming bioink laden with tumor cells was combined with digital light processing–based bioprinting for developing native-like Alk+ lung cancer tissue-mimics with both structural and functional relevancy. It is anticipated that our proposed methodology will pave new avenues for both fields of tissue diagnostics and 3D bioprinting significantly expanding their capacities, scope, and sustainability.

Impact statement

We provide the first study of using the three-dimensional bioprinting technology to produce control tissue-mimics for applications in diagnostic, prognostic, and predictive assays. Specifically, a cell-laden micropore-forming bioink was used with digital light processing bioprinting to create a native-like human Alk+ lung cancer tissue model that was both structurally and functionally similar to its native counterpart. Our method provides a new concept in obtaining a reproducible and secure supply of customizable control tissues with standardized cell type, tissue architecture, and preanalytics of interest.