Description du projet
De nouvelles greffes osseuses conçues par ingénierie tissulaire
Le tissu osseux conçu par ingénierie tissulaire présente de nombreux avantages par rapport aux greffes osseuses naturelles, notamment en termes de sécurité et du fait de leur approvisionnement illimité. Cependant, les méthodes d’ingénierie actuelles ne permettent pas de créer de grands greffons vascularisés pouvant faire l’objet d’une intégration et d’un remodelage in vivo. Pour résoudre ce problème, le projet REBORN, financé par l’UE, propose de combiner des biomatériaux basés sur des protéines obtenues à partir de la membrane amniotique et des cellules du cordon ombilical pour mettre au point un dispositif en 3D capable de soutenir la formation du tissu osseux. Les scientifiques utiliseront des hydrogels pour fournir des repères géométriques, mécaniques et topographiques, ainsi que des facteurs bioactifs solubles pour stimuler la différenciation cellulaire et recréer la niche de la moelle osseuse.
Objectif
Engineered bone tissue has been viewed as a potential alternative to the traditional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice as it was not yet possible to fully recreate the right conditions to produce relevant large vascularized grafts and enabling their in vivo integration and remodelling. REBORN proposes rather unique toolboxes combining bionstructive biomaterials only based on human proteins obtained from the amniotic membrane (AM) and cells from the umbilical/blood cord for the ground-breaking advances of engineering totally time-self-regulated complex 3D devices, able to adjust the cascade of processes leading to faster high-quality and vascularized new bone tissue formation with minimum pre-processing of cells. Proteins from AM will be chemically modified with bioorthogonal clickable moieties enabling their selective association during the fabrication of liquified pockets or hydrogels. Perm-selective AM-protein membranes will be formed at the interface of aqueous-based emulsions to produce liquified pockets confining all necessary ingredients for internal in vitro tissue development to recreate the bone niche including: (i) the correct cells’ ratio, (ii) hydrogel MicroBlocks that will provide geometrical, mechanical and topographic cues to control cellular behaviour and (iii) bioactive soluble factors. Jammed liquified pockets will be assembled into a final desired implantable device, bound by the developed hydrogels, with clinically relevant size, shape and structural integrity, using non-conventional 3D bioprinting processing methodologies or by physical fixation in bioinspired, periosteum-like, regenerative membranes. Advanced techniques will be employed to characterise the new tissue developed in the hybrid devices, from the ultrastructure of the mineral/organic component, including under distinctive dynamic culturing conditions.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-ADG - Advanced GrantInstitution d’accueil
3810-193 Aveiro
Portugal