RICOSTRUZIONE CRANICA DOPO TRAUMA LESIONE CEREBRALE MEDIANTE IMPIANTI FUNZIONALIZZATI STAMPATI IN 3D

Traumatic Brain Injuries (TBIs) are caused by hits, blow or jolts to the head, and they affect both the cranium and the cerebral tissue underneath. The consequences vary depending on the severity of the damage: whenever it is particularly high, cranium reconstruction might be needed. Over the centuries, this has been done by implanting prosthetics of different materials; nowadays, strategies combining the classical approach and a more modern tissue regeneration one are in place to offer the best possible outcome for cranial reconstruction. In fact, tissue engineering is set on providing a strategy allowing for natural bone regeneration and avoiding infection or other troublesome phenomena in the site of implant. In particular, this work intends to propose a new approach based on functionalised, 3D-printed polymeric implants combined with a Drug Delivery System (DDS), to address both the lack of bone and the need to restore natural, living tissue without occurrence of inflammation and subsequent issues. Porous poly-lactic acid (PLA) structures were printed by the Fused Deposition Modelling (FDM) technique, coated in hydroxyapatite (HAp) to provide osteoinductive properties, and implemented with a DDS based on polycaprolactone (PCL) microparticles loaded with dexamethasone, an anti-inflammatory drug. Each step of this strategy has been carefully studied and improved. Thorough characterisation was performed to ensure the suitability of each step of the implant production. Among the used techniques, optical and electronic microscopy, Differential Scanning Calorimetry, Fourier Transform Infrared Spectroscopy, mechanical tests and biological assays. The results of the characterisation were deemed satisfactory enough, allowing to identify both the strong suits of the produced structures and their criticalities, in order to be able to address them in the future. The porosity and the mechanical and thermal properties of the porous poly-lactic acid structures were deemed adequate; the hydroxyapatite coating, which can be performed in more than one way, actually succeeded in providing homogeneity and some of the needed properties; the developed DDS grants a modulated release of anti-inflammatory without negatively affecting cellular viability, and its incorporation onto the structures through different approaches was successful. Some parameters and synthetic steps of this implant production still need refinement: on one hand, a more detailed characterisation is needed to ensure an in-depth knowledge of the final implants in 2 every aspect; on the other hand, there is still room for improvement, namely in the modulated drug release field and in the incorporation of the DDS onto the printed structures. Future efforts should therefore focus on the establishment of fixed protocols, both to define the procedures entailing the best yields for the desired results and to ensure the reproducibility of the operations

Le lesioni craniche traumatiche (TBI) sono causate da colpi, colpi o scosse alla testa e colpiscono sia il cranio che il tessuto cerebrale sottostante. Le conseguenze variano a seconda della gravità del danno: quando è particolarmente grave, potrebbe essere necessaria una ricostruzione cranica. Nel corso dei secoli, questo è stato fatto impiantando protesi di materiali diversi; oggigiorno, sono in atto strategie che combinano l'approccio classico con uno più moderno di rigenerazione tissutale per offrire il miglior risultato possibile per la ricostruzione cranica. L'ingegneria tissutale, infatti, si propone di fornire una strategia che consenta la rigenerazione ossea naturale ed eviti infezioni o altri fenomeni problematici nel sito di impianto. I