Unlocking the Potential Role of Decellularized Biological Scaffolds as a 3D Radiobiological Model for Low- and High-LET Irradiation

Simple Summary Two-dimensional (2D) models are unable to mimic the intricacies of the reaction in the natural tumor microenvironment to the irradiation, biological and architectural complexity, or dynamic nature of the many tissues. These features can be recreated using a decellularized extracellular matrix (ECM), such as bioscaffolds. We hypothesized that bioscaffolds can be a feasible and effective three-dimensional (3D) model, worthwhile also for radiobiological aims. To test our hypothesis, two cell lines (HMV-II and PANC-1) were seeded in decellularized porcine liver-derived scaffolds and irradiated with carbon ions (high-LET irradiation) and photons (low-LET irradiation). For the first time in the literature, we found that the 3D environment provided by the bioscaffolds was suitable for radiobiological research as well as being cost-effective. This model provides the opportunity to explore the biological consequences of different radiation modalities over prolonged periods of time.Abstract Introduction: Decellularized extracellular matrix (ECM) bioscaffolds have emerged as a promising three-dimensional (3D) model, but so far there are no data concerning their use in radiobiological studies. Material and Methods: We seeded two well-known radioresistant cell lines (HMV-II and PANC-1) in decellularized porcine liver-derived scaffolds and irradiated them with both high- (Carbon Ions) and low- (Photons) Linear Energy Transfer (LET) radiation in order to test whether a natural 3D-bioscaffold might be a useful tool for radiobiological research and to achieve an evaluation that could be as near as possible to what happens in vivo. Results: Biological scaffolds provided a favorable 3D environment for cell proliferation and expansion. Cells did not show signs of dedifferentiation and retained their distinct phenotype coherently with their anatomopathological and clinical behaviors. The radiobiological response to high LET was higher for HMV-II and PANC-1 compared to the low LET. In particular, Carbon Ions reduced the melanogenesis in HMV-II and induced more cytopathic effects and the substantial cell deterioration of both cell lines compared to photons. Conclusions: In addition to offering a suitable 3D model for radiobiological research and an appropriate setting for preclinical oncological analysis, we can attest that bioscaffolds seemed cost-effective due to their ease of use, low maintenance requirements, and lack of complex technology