Complex biomaterials: engineering mimetic epithelial tissue

Lung adenocarcinoma (LADC) is an aggressive malignancy with high mortality. The proposed research offers a novel experimental environment to study the steps of cancer progression. By its engineered nature, the developed device is expected to be useful for high-throughput studies where the same environment is replicated and each replica is used to evaluate a treatment regimen. Such approaches are expected to lead us to improved personalized medicine where the most efficient treatment can be offered knowing the particular features of the tumor and the genetic makeup of the patient.

Over the course of the project, we combined bioengineering, quantitative modeling, and cancer research to better understand barrier tissues and disease processes. A major focus was the development of advanced in vitro tissue models. We established biomimetic kidney tubules, human skin equivalents for controlled drug permeability testing, and various epithelial barrier models on transwell inserts, including a detailed evaluation of Vero E6 cells as a functional barrier system with defined TEER values, permeability coefficients, and calcium-sensitive tight junctions. We introduced automated and millifluidic sampling approaches combined with mathematical corrections for systematic artifacts such as residual volume and adsorption. We proposed and validated a three-compartment transport model capturing membrane diffusion, cellular sequestration, and metabolic loss, enabling more mechanistic interpretation than conventional apparent permeability measures. These methods were applied to characterize compounds including petasol, demonstrating efficient epithelial transport with minimal intracellular accumulation. In cancer research, we contributed advanced in vitro models to studies of lung metastasis, mesothelioma vascularization, and to the better understanding of small cell lung cancer biology, heterogeneity, molecular subtypes and therapy. Overall, the project resulted in 52 publications. The current FWF grant is acknowledged in all of the aforementioned publications. We thank the FWF for their support.