Full human-based multi-scale constructs with jammed regenerative pockets for bone engineering

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.