MAXINNERV

Vascularization is one of the most pressing challenges in tissue engineering, as it is essential for tissue survival giving access to nutrients and oxygen exchange. However, implanted engineered constructs also lack neural networks and depend on host bed-induced innervation to integrate with the native nerve supply. Sufficient attention has not been given to promoting appropriate connections between the host neurovascular networks and engineered implants. We hypothesize that Schwann cells activity fosters neurovascular recruitment, promoting bone regeneration. The MAXINNERV project proposes to develop innervated and vascularized spheroids for bone regeneration, (i) in vitro to study the nervous and vascular tissue recruitment and communication, and (ii) in vivo as a spheroid-based strategy to induce neurovascular recruitment during regeneration. We will (i) use human inducible pluripotent stem cells (iPSC) to obtain sensory neurons (iPSC-SNs) and Schwann cells (iPSC-SCs), (ii) produce spheroids containing dental pulp mesenchymal stromal cells, endothelial cells, and iPSC-SCs (here called neurovascular spheroids), (iii) develop a model of innervated neurovascular spheroid-on-a-chip and (iv) evaluate the craniofacial bone regeneration potential of neurovascular spheroids in vivo. This proposition paves the way for novel breakthroughs from basic to translational research, by (i) developing a 3D cellular model that allows the study of nervous, vascular, and bone tissue communication; (ii) creating a physiological model of innervated vascularized spheroids-on-a-chip capable of identifying target molecules that guide the process of innervation, vascularization, and osteogenesis; and (iii) proposing a cellular strategy to promote implant integration through neurovascular colonization.