Bone Tissue Engineering: structures and strategies for functional scaffold design and evaluation

Skeletal tissue has a good ability to self-regenerate after injury through the processes of bone healing. However, bone can suffer from a wide range of pathologies, cancers or congenital defects which lead to loss of bone mass and density. Current progresses in tissue engineering have shown great potential for creating biological alternatives and new perspectives for the treatment of bone damage and defects. In this approach, scaffolding plays a pivotal role. In particular, the principles of biomimesis have to be followed and the scaffolds have to be designed to this purpose. Furthermore, these tissue engineered systems have not only to support and guide the new tissue formation, but they have to induce a complete tissue functionality. The aim of this research work was the application of these advanced principles to produce and evaluate scaffolds for bone regeneration. Starting from the idea to mimic the extracellular matrix (ECM), template that characterizes the early step of the bone healing process, we design scaffolds for the evaluation of biological outputs considering the initial ECM produced by cells. We used two polymers, naturally (silk fibroin) or synthetically (poly-d,l-lactic acid) derived, and we modulated scaffold geometry (random vs ordered pore distribution), pore size and chemical composition, combining spongy and fibrous structures. The scaffolds were indeed considered as models, to investigate if they control cell production of type I collagen, principle component of the natural template for the final mineralization. Moreover, due to the key role of vessel formation in tissue engineering and the correlation between osteoblasts and endothelial cells, the influence of the scaffolds on angiogenesis and vascularisation was assessed. The innovation of this study consists in the evaluation shift from the final healing stage to the earlier stages. In fact, the results emphasize the possibility to correlate the scaffold morphology to type I collagen assembly, which in turn affects the final mineralization process, allowing to evaluate the tissue produced by osteoblasts from the first steps of bone formation. Moreover, we were able to control some cell behaviours changing construct properties. In a future research, a segmental bone defect models should be considered to better characterize the role of scaffold features during bone healing process and to determine if it would be better to use scaffolds which favour angiogenesis or mineralization to speed up a physiological bone regeneration process.