Rega, Andrea (2022) Design of 3D additively manufactured scaffolds and collaborative biomanufacturing systems for tissue engineering. [Tesi di dottorato]

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Additive Manufacturing (AM) technologies represent a useful and cost-effective tool for the timely fabrication of geometrically complex objects. The suitability of AM in achieving complex shapes, the accuracy, the reproducibility, and the high degree of automation of the processes, have contributed to affirm the great utility of these technologies in several contexts, including medical and healthcare. AM technologies enabled to rapidly fabricate medical devices meeting patient-specific requirements and, as a result, they have greatly enhanced routine clinical procedures. This work provides an overview of the different AM classes as classified by the ISO reference standards, then focusing on the main applications of these technologies in the medical field. In the field of Tissue Engineering (TE), AM enables the designing and manufacturing of customized scaffolds with complex shapes, lightweight, and tailored properties, mimicking closely the heterogeneity and complexity of tissues and organs to substitute or promote tissue healing and regeneration. Bone tissue regeneration has particularly benefited from these scaffold-based approaches. The usage of scaffolds as temporary three-dimensional frameworks to provide structural support for cell growth, proliferation and adhesion during the regenerative process, the ideal features of such constructs, are the main topics addressed by this work. A focus on the porosity effect on both biological and mechanical features of scaffolds is presented. Magnetic nanocomposite scaffolds were designed and manufactured by means of AM to investigate the possible enhancing in bone tissue regeneration due to the magnetic characteristics of the constructs. The work reports the analysis of the role of magnetic features on biological performance. Even the mechanical characteristics of scaffolds were improved by using magnetic nanoparticles (MNPs) as reinforcement of the polymeric matrices. Despite the encouraging outcomes of scaffold-based TE, the commercial translation of Additive Manufacturing technologies for scaffold fabrication is still a challenge. The production methodology of 3D scaffolds for tissue regeneration is a complex and discontinuous process involving several stages going from the isolation of the stem cells to the in vitro dynamic cell culture. Even though in this scenario industries are increasingly implementing automated robotic systems, current technologies are not sufficient for the development of large industrial scale scaffold fabrication. Accordingly, a relevant improvement could raise from the implementation of a modern collaborative workplace in an existing production line, combining strength endurance and accuracy of cobots, with intelligence, flexibility and adaptability of the human being. In a such system, the drawbacks related to the low level of process control, low productivity and risk of contaminations may be solved. Therefore, the current work also proposes a systematic approach to the design of collaborative biomanufacturing systems. The last chapter of this work provides a further insight into the potential to upscale the scaffolds manufacturing process, taking advantage of the possibilities given from the Human-Robot Collaboration (HRC) and gives evidence of critical features for workplace definition.

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