DNA double-strand breaks (DSB) are among the most harmful DNA lesions induced by ionizing radiation (IR). Although the induction and repair of radiation-induced DSB is well studied for acute irradiation, responses to DSB produced by chronic IR exposures are poorly understood, especially in human stem cells. The aim of this study was to examine the formation of DSB markers (γH2AX and phosphorylated kinase ATM, pATM, foci) in human mesenchymal stem cells (MSCs) exposed to chronic gamma-radiation (0.1 mGy/min) in comparison with acute irradiation (30 mGy/min) at cumulative doses of 30, 100, 160, 240 and 300 mGy. A linear dose-dependent increase in the number of both γH2AX and pATM foci, as well as co-localized γH2AX/pATM foci (“true” DSB), were observed after an acute radiation exposure. In contrast, the response of MSCs to a chronic low dose-rate IR exposure deviated from linearity towards a threshold model, for γH2AX, pATM foci and γH2AX/pATM foci, with an indication of a “plateau”. The state of equilibrium between newly formed DSB at a low rate during the protracted exposure time and the elimination of a fraction of DSB is proposed as a mechanistic explanation of the non-linear DSB responses following a low dose-rate irradiation. This notion is supported by the observation of the elimination of a substantial fraction of DSB 6 h after the cessation of the exposures. Our results demonstrate non-linear dose responses for γH2AX and pATM foci in human MSCs exposed to low dose-rate IR and showed the existence of a threshold, which may have implications for radiation protection in humans.

The study was aimed at the applicability of a bioink based on 4% collagen and chondrocytes for de novo cartilage formation. Extrusion-based bioprinting was used for the biofabrication. The printing parameters were tuned to obtain stable material flow. In vivo data proved the ability of the tested bioink to form a cartilage within five to six weeks after the subcutaneous scaffold implantation. Certain areas of cartilage formation were detected as early as in one week. The resulting cartilage tissue had a distinctive structure with groups of isogenic cells as well as a high content of glycosaminoglycans and type II collagen.

During biofabrication, a tissue scaffold may require temporary support. The aim of this study was to develop an approach of human thyroid cartilage scaffold temporal support formation. The scaffold 3D-model was based on DICOM images. XY plane projections were used to form scaffold supporting part. To verify the technique, collagen hydrogel was chosen as the main scaffold component. Gelatin was applied for the supporting part. To test the applicability of the approach, a model of thyroid cartilage scaffold with the support was printed. The scaffold corresponded to a given model, although some discrepancy in geometry was observed during verification by computed tomography.