3D Printing and bioprinting of osteomimetic materials for 3D in vitro models and tissue repair applications

Bone disorders have severe impact on body functions and quality life, and no satisfying therapies exist yet. The current models for bone disease study are scarcely predictive and the options existing for therapy fail for complex systems. To mimic and/or restore bone, 3D printing/bioprinting allows the creation of 3D structures with different materials compositions, properties, and designs. In this study, 3D printing/bioprinting has been explored for (i) 3D in vitro tumor models and (ii) regenerative medicine. Tumor models have been developed by investigating different bioinks (i.e., alginate, modified gelatin) enriched by hydroxyapatite nanoparticles to increase printing fidelity and increase biomimicry level, thus mimicking the organic and inorganic phase of bone. High Saos-2 cell viability was obtained, and the promotion of spheroids clusters as occurring in vivo was observed. To develop new syntethic bone grafts, two approaches have been explored. In the first, novel magnesium-phosphate scaffolds have been investigated by extrusion-based 3D printing for spinal fusion. 3D printing process and parameters have been optimized to obtain custom-shaped structures, with competent mechanical properties. The 3D printed structures have been combined to alginate porous structures created by a novel ice-templating technique, to be loaded by antibiotic drug to address infection prevention. Promising results in terms of planktonic growth inhibition was obtained. In the second strategy, marine waste precursors have been considered for the conversion in biogenic HA by using a mild-wet conversion method with different parameters. The HA/carbonate ratio conversion efficacy was analysed for each precursor (by FTIR and SEM), and the best conditions were combined to alginate to develop a composite structure. The composite paste was successfully employed in custom-modified 3D printer for the obtainment of 3D printed stable scaffolds. In conclusion, the osteomimetic materials developed in this study for bone models and synthetic grafts are promising in bone field.

SPHERA, a new Italian convection-permitting regional reanalysis: improving heavy-rainfall representation and describing hail-prone environments

Extreme weather events related to deep convection are high-impact critical phenomena whose reliable numerical simulation is still challenging. High-resolution (convection-permitting) modeling setups allow to switch off physical parameterizations accountable for substantial errors in convection representation. A new convection-permitting reanalysis over Italy (SPHERA) has been produced at ARPAE to enhance the representation and understanding of extreme weather situations. SPHERA is obtained through a dynamical downscaling of the global reanalysis ERA5 using the non-hydrostatic model COSMO at 2.2 km grid spacing over 1995-2020. This thesis aims to verify the expectations placed on SPHERA by analyzing two weather phenomena that are particularly challenging to simulate: heavy rainfall and hail. A quantitative statistical analysis over Italy during 2003-2017 for daily and hourly precipitation is presented to compare the performance of SPHERA with its driver ERA5 considering the national network of rain gauges as reference. Furthermore, two extreme precipitation events are deeply investigated. SPHERA shows a quantitative added skill over ERA5 for moderate to severe and rapid accumulations in terms of adherence to the observations, higher detailing of the spatial fields, and more precise temporal matching. These results prompted the use of SPHERA for the investigation of hailstorms, for which the combination of multiple information is crucial to reduce the substantial uncertainties permeating their understanding. A proxy for hail is developed by combining hail-favoring environmental numerical predictors with observations of ESWD hail reports and satellite overshooting top detections. The procedure is applied to the extended summer season (April-October) of 2016-2018 over the whole SPHERA spatial domain. The results indicate maximum hail likelihood over pre-Alpine regions and the northern Adriatic sea around 15 UTC in June-July, in agreement with recent European hail climatologies. The method demonstrates enhanced performance in case of severe hail occurrences and the ability to separate between ambient signatures depending on hail severity.