New developments on tissue engineering strategies should realize the complexity of tissue remodelling and the inter-dependency of many variables associated to stem cells and biomaterials interactions. ComplexiTE proposes an integrated approach to address such multiple factors in which different innovative methodologies are implemented, aiming at developing tissue-like substitutes with enhanced in vivo functionality. Several ground-breaking advances are expected to be achieved, including: i) improved methodologies for isolation and expansion of sub-populations of stem cells derived from not so explored sources such as adipose tissue and amniotic fluid; ii) radically new methods to monitor human stem cells behaviour in vivo; iii) new macromolecules isolated from renewable resources, especially from marine origin; iv) combinations of liquid volumes mingling biomaterials and distinct stem cells, generating hydrogel beads upon adequate cross-linking reactions; v) optimised culture of the produced beads in adequate 3D bioreactors and a novel selection method to sort the beads that show a (pre-defined) positive biological reading; vi) random 3D arrays validated by identifying the natural polymers and cells composing the positive beads; v) 2D arrays of selected hydrogel spots for brand new in vivo tests, in which each spot of the implanted chip may be evaluated within the living animal using adequate imaging methods; vi) new porous scaffolds of the best combinations formed by particles agglomeration or fiber-based rapid-prototyping. The ultimate goal of this proposal is to develop breakthrough research specifically focused on the above mentioned key issues and radically innovative approaches to produce and scale-up new tissue engineering strategies that are both industrially and clinically relevant, by mastering the inherent complexity associated to the correct selection among a great number of combinations of possible biomaterials, stem cells and culturing conditions.
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