Evaluating the Suitability of 3D Bioprinted Samples for Experimental Radiotherapy: A Pilot Study

Abstract

Radiotherapy is an important component in the treatment of lung cancer, one of the most common cancers worldwide, frequently resulting in death within only a few years of diagnosis. In order to evaluate new therapeutic approaches and compare their efficiency with regard to tumour control at a pre-clinical stage, it is important to develop standardized samples which can serve as inter-institutional outcome controls, independent of differences in local technical parameters or specific techniques. Recent developments in 3D bioprinting techniques could provide a sophisticated solution to this challenge. We have conducted a pilot project to evaluate the suitability of standardized samples generated from 3D printed human lung cancer cells in radiotherapy studies. The samples were irradiated at high dose rates using both broad beam and microbeam techniques. We found the 3D printed constructs to be sufficiently mechanically stable for use in microbeam studies with peak doses up to 400 Gy to test for cytotoxicity, DNA damage, and cancer cell death in vitro. The results of this study show how 3D structures generated from human lung cancer cells in an additive printing process can be used to study the effects of radiotherapy in a standardized manner.

Generation of a Perfusable 3D Lung Cancer Model by Digital Light Processing

“…Three-dimensional organ models have developed as an alternative approach to conventional animal experiments, which are composed of human cells and, at the same time, may help to reduce the number of animal experiments [ 33 ]. Bioprinting is one of the most promising technologies for producing disease models for oncology research and can be used to develop anticancer substances and optimize irradiation procedures [ 20 , 34 ]. Compared to other techniques for the generation of 3D cultures, such as organoid formation, bioprinting has the advantage of allowing for the computer-based design of 3D objects with a predefined structure [ 18 , 35 , 36 ].…”

SERS-Active Printable Hydrogel for 3D Cell Culture and Imaging

“…3D printing has gained extensive utilization in producing highly reproducible 3D environments with precise structures for 3D cell growth. ,, In 3D bioprinting, hydrogel ink fluidity is crucial. For this purpose, gelatin is usually mixed with alginate to initiate gelation prior to bioprinting. , Previous studies have shown that an ink consisting of ∼2% (w/v) alginate and ∼3% (w/v) gelatin has good elasticity and loss modulus that are favorable for extrusion printing and cell viability. , These concentrations also ensure the robust stability of the printed products for cell culture process Figure a shows a hydrogel ink prepared using this alginate/gelatin concentration following loading into a 3D printing cartridge.…”

“…44,45 Previous studies have shown that an ink consisting of ∼2% (w/v) alginate and ∼3% (w/v) gelatin has good elasticity and loss modulus that are favorable for extrusion printing and cell viability. 39,46 These concentrations also ensure the robust stability of the printed products for cell culture process. 39 Figure 2a shows a hydrogel ink prepared using this alginate/gelatin concentration following loading into a 3D printing cartridge.…”

The Microbeam Insert at the White Beam Beamline P61A at the Synchrotron PETRA III/DESY: A New Tool for High Dose Rate Irradiation Research

“…5 × 10 mm sample generated in a 3D bioprinting technique from malignant tumor cells. The bioprinting technique has been previously described [ 29 ]. 3D bioprinted material can be reproducibly custom shaped during the printing process, to fit the requirements of each individual experiment.…”

“…In August 2016, we conducted a first MRT feasibility study at the monochromatic beamline P07. Based on the results of that experiment and subsequent studies at the monochromatic beamline P21.2 [ 29 ], we decided to develop a dedicated setup for biomedical high dose rate irradiation studies at the new white beam beamline P61A which was, at that time, designed and constructed under the leadership of the Helmholtz Centre Geesthacht (now HEREON). The safety tests for this new beamline were passed in November 2020.…”