Development of newly conceived biomimetic nano-structured biomaterials as scaffolds for bone and osteochondral regeneration

The present research thesis was focused on the development of new biomaterials and devices for application in regenerative medicine, particularly in the repair/regeneration of bone and osteochondral regions affected by degenerative diseases such as Osteoarthritis and Osteoporosis or serious traumas. More specifically, the work was focused on the synthesis and physico-chemical-morphological characterization of: i) a new superparamagnetic apatite phase; ii) new biomimetic superparamagnetic bone and osteochondral scaffolds; iii) new bioactive bone cements for regenerative vertebroplasty. The new bio-devices were designed to exhibit high biomimicry with hard human tissues and with functionality promoting faster tissue repair and improved texturing. In particular, recent trends in tissue regeneration indicate magnetism as a new tool to stimulate cells towards tissue formation and organization; in this perspective a new superparamagnetic apatite was synthesized by doping apatite lattice with di-and trivalent iron ions during synthesis. This finding was the pin to synthesize newly conceived superparamagnetic bone and osteochondral scaffolds by reproducing in laboratory the biological processes yielding the formation of new bone, i.e. the self-assembly/organization of collagen fibrils and heterogeneous nucleation of nanosized, ionically substituted apatite mimicking the mineral part of bone. The new scaffolds can be magnetically switched on/off and function as workstations guiding fast tissue regeneration by minimally invasive and more efficient approaches. Moreover, in the view of specific treatments for patients affected by osteoporosis or traumas involving vertebrae weakening or fracture, the present work was also dedicated to the development of new self-setting injectable pastes based on strontium-substituted calcium phosphates, able to harden in vivo and transform into strontium-substituted hydroxyapatite. The addition of strontium may provide an anti-osteoporotic effect, aiding to restore the physiologic bone turnover. The ceramic-based paste was also added with bio-polymers, able to be progressively resorbed thus creating additional porosity in the cement body that favour cell colonization and osseointegration.

Development of Core Design Methods and Tools for Gen-IV Heavy Liquid Metal Cooled Reactors

Heavy Liquid Metal Cooled Reactors are among the concepts, fostered by the GIF, as potentially able to comply with stringent safety, economical, sustainability, proliferation resistance and physical protection requirements. The increasing interest around these innovative systems has highlighted the lack of tools specifically dedicated to their core design stage. The present PhD thesis summarizes the three years effort of, partially, closing the mentioned gap, by rationally defining the role of codes in core design and by creating a development methodology for core design-oriented codes (DOCs) and its subsequent application to the most needed design areas. The covered fields are, in particular, the fuel assembly thermal-hydraulics and the fuel pin thermo-mechanics. Regarding the former, following the established methodology, the sub-channel code ANTEO+ has been conceived. Initially restricted to the forced convection regime and subsequently extended to the mixed one, ANTEO+, via a thorough validation campaign, has been demonstrated a reliable tool for design applications. Concerning the fuel pin thermo-mechanics, the will to include safety-related considerations at the outset of the pin dimensioning process, has given birth to the safety-informed DOC TEMIDE. The proposed DOC development methodology has also been applied to TEMIDE; given the complex interdependence patterns among the numerous phenomena involved in an irradiated fuel pin, to optimize the code final structure, a sensitivity analysis has been performed, in the anticipated application domain. The development methodology has also been tested in the verification and validation phases; the latter, due to the low availability of experiments truly representative of TEMIDE's application domain, has only been a preliminary attempt to test TEMIDE's capabilities in fulfilling the DOC requirements upon which it has been built. In general, the capability of the proposed development methodology for DOCs in delivering tools helping the core designer in preliminary setting the system configuration has been proven.

Development of a Computer-Based methodology for tolerance selection and optimization applied to the automotive sector

The design optimization of industrial products has always been an essential activity to improve product quality while reducing time-to-market and production costs. Although cost management is very complex and comprises all phases of the product life cycle, the control of geometrical and dimensional variations, known as Dimensional Management (DM), allows compliance with product and process requirements. Hence, the tolerance-cost optimization becomes the main practice to provide an effective application of Design for Tolerancing (DfT) and Design to Cost (DtC) approaches by enabling a connection between product tolerances and associated manufacturing costs. However, despite the growing interest in this topic, a profitable application in the industry of these techniques is hampered by their complexity: the definition of a systematic framework is the key element to improving design optimization, enhancing the concurrent use of Computer-Aided tools and Model-Based Definition (MBD) practices. The present doctorate research aims to define and develop an integrated methodology for product/process design optimization, to better exploit the new capabilities of advanced simulations and tools. By implementing predictive models and multi-disciplinary optimization, a Computer-Aided Integrated framework for tolerance-cost optimization has been proposed to allow the integration of DfT and DtC approaches and their direct application for the design of automotive components. Several case studies have been considered, with the final application of the integrated framework on a high-performance V12 engine assembly, to achieve both functional targets and cost reduction. From a scientific point of view, the proposed methodology provides an improvement for the tolerance-cost optimization of industrial components. The integration of theoretical approaches and Computer-Aided tools allows to analyse the influence of tolerances on both product performance and manufacturing costs. The case studies proved the suitability of the methodology for its application in the industrial field, providing the identification of further areas for improvement and refinement.

Development of molecular-level switches and implementation into novel nanostructures and smart materials

The work presented in this thesis deals with the design, synthesis and investigation of (supra)molecular switches, and their implementation into novel nanostructures and smart devices. Part A deals with investigation of fundamental properties of Donor Acceptor Stenhouse Adducts (DASAs) as well as their implementation into polymer matrices in order to construct novel smart materials. Part B deals with the implementation of azobenzene photoswitches into pseudorotaxanes and the investigation of the effect of light-driven isomerization on the self-assembly and disassembly processes.