Biocompósitos eletrofiados e microfabricação 3D em engenharia do tecido ósseo

Abstract

Bone tissue regeneration is still an important challenge in orthopedics and traumatology.Despite the natural ability of bone repair, a trauma beyond the critical limit (critical fracture) cannot be regenerated. Tissue Engineering is a multidisciplinary field that applies the principles of engineering and biological sciences to the development of biological substitutes that restore, maintain or improve the tissue function or of an organ as a whole. The aim of this work was to develop osteogenic and mechanically improved biomimetic scaffolds for bone tissue engineering; to improve the vascularization of a bone tissue engineered implant by the design and development of a suturable vessel graft embedded in hydrogels for 3D biofabrication. Biodegradable PCL membranes for guided bone regeneration, obtained by electrospinning, reinforced with various ratios of natural nanocomposites obtained from cellulose nanocrystals (CNCs) were produced.Results showed an improvement of mechanical properties, in the degree of crystallinity and in the melting temperature according to the ratio of cellulose nanocrystals. I employed Biosilicate® as bioactive phase into these membranes. The Biosilicate®, combined with the cellulose nanocrystals, considerably improved their mechanical properties. Osteoblasts were able to proliferate and biomineralize in these membranes. Thus, a biomimetic and biodegradable membranes, with osteogenicity and improved mechanical properties for guided bone regeneration and bone tissue engineering were developed. In order to improve the vascularization of bone tissue engineering constructs, new GelMA-CNC composites were developed. Cell-laden GelMA-CNC hydrogels with endothelial cells were biofabricated. Endothelial cells were able sprout and to organize in tubules. As rapid vascularization strategy, a rapid degrading biomimetic suturable graft obtained from electrospun membranes fusing, in order to allow endothelial cell migration from the vascular graft to the bone-like grafts and, following, new capillary formation, was manufactured. A porous pattern over the suturable grafts was fabricated by laser micromachining.The obtained elastic scaffolds were suturable and supported stress and recoil. The scaffolds are autoclavable and possess no in vitro toxicity. The porous patterned created on the suturable grafts allowed the endothelial cell towards the 3D culture of osteoblasts in GelMA, and 3D structures formed from the interaction of endothelial cells and osteoblasts were observed. Therefore, this strategy can potentially be employed to enhance the size and the survival biofabricated bone implants, accelerating the clinical translation of bone tissue engineering.