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

Author:

Charalampopoulou Alexandra12ORCID,Barcellini Amelia34ORCID,Peloso Andrea5,Vanoli Alessandro67ORCID,Cesari Stefania67ORCID,Icaro Cornaglia Antonia8,Bistika Margarita9,Croce Stefania10,Cobianchi Lorenzo111213ORCID,Ivaldi Giovanni Battista14ORCID,Locati Laura Deborah315ORCID,Magro Giuseppe16ORCID,Tabarelli de Fatis Paola17,Pullia Marco Giuseppe18ORCID,Orlandi Ester412ORCID,Facoetti Angelica1ORCID

Affiliation:

1. CNAO National Center for Oncological Hadrontherapy, Radiobiology Unit, Research and Development Department, 27100 Pavia, Italy

2. Hadron Academy PhD Course, School for Advanced Studies (IUSS), 27100 Pavia, Italy

3. Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy

4. CNAO National Center for Oncological Hadrontherapy, Radiation Oncology Unit, Clinical Department, 27100 Pavia, Italy

5. Division of Visceral Surgery, Department of Surgery, Geneva University Hospitals, 1205 Geneva, Switzerland

6. Unit of Anatomic Pathology, Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy

7. Unit of Anatomic Pathology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy

8. Unit of Histology and Embryology, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy

9. Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy

10. Cell Factory, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy

11. Department of General Surgery, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy

12. Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy

13. Collegium Medicum, University of Social Sciences, 90-419 Łodz, Poland

14. Istituti Clinici Scientific Maugeri IRCCS, Radiation Oncology Department, 27100 Pavia, Italy

15. Medical Oncology Unit, Istituti Clinici Scientific Maugeri IRCCS, 27100 Pavia, Italy

16. CNAO National Center for Oncological Hadrontherapy, Medical Physics Unit, Clinical Department, 27100 Pavia, Italy

17. Medical Physic Unit, Istituti Clinici Scientific Maugeri IRCCS, 27100 Pavia, Italy

18. Research and Development Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy

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

Publisher

MDPI AG

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