Anagrafe della ricerca

Goal of DESIRE is to engineer and build innovative osteochondral (OC) scaffolds to boost the regeneration of either bone and cartilage tissues beyond the levels reached by state-of-art products. Scaffolds, designed to maximize the formation of new bone and cartilage, will be fabricated by Stereolithography (SL), allowing to achieve unprecedented control over scaffold inner architecture. New biopolymers for SL will be developed, to match 3D printing technical specifications with biological and mechanical requirements of the constructs. Scaffolds will be seeded with human Mesenchymal Stem Cells (MSCs) under perfusion culturing conditions, as the most advanced technique to prompt cells differentiation. Ministero dell'Università e della Ricerca MUR - BANDO 2022 Scaffolds will be designed as a single structure, but with a gradual/adjustable variation of the inner features from bone to cartilage-side, also taking care of their transition zone. Design will be supported by Finite Element Method analysis, where on the ground of mechanical properties and permeability of constituent tissues, different sets of porosity features (amount, size and shape) will be predicted, to deepen their role on cells differentiation. A selected number of modelled structures (from 3 to 5) will be designed based on the minimal surface structures approach, able to satisfy the modelled inner features and their adjustable gradation along the scaffold. New photocurable polymer inks for SL will be developed, by considering both natural polymers (prompting cell adhesion and differentiation, but low mechanical strength) and synthetic polymers (higher mechanical response but high viscosity and lower biocompatibility). Bioinks will be conceived as a blend of natural and synthetic polymers, also including the discrete addition of calcium phosphate particles for yielding the bone-like part of the scaffold, providing a unique printable extra cellular matrix-like formulation. The challenge in the SL process will be to fabricate scaffolds with the tuned inner features and to build structural-compositional graded structures while satisfying accuracy and reproducibility requirements. 3D construct will be finally cultured under perfusion bioreactor, to boost cells differentiation into both bone and cartilage-like cells, deepening the role of the inner features in prompting cells differentiation. The ambition of DESIRE is to quantitatively asses, by histological and morphometric analyses, the higher OC regeneration potential of the developed scaffolds compared to current available products. In DESIRE, the synergic combination of the most advanced strategies in OC scaffolds are addressed, namely new printable bioinks, tailored design of scaffold architecture, SL technology and perfusion bioreactor, thus boosting knowledge, technologies and clinical practices.