Bioinspired Multicellular Mandibular Constructs for Craniofacial Bone Regeneration

Objective

Craniofacial bone defects caused by trauma, infection, or tumour resection remain a major clinical challenge, with current treatment—autologous bone grafting—limited by donor site morbidity, insufficient volume, and poor restoration of function. Mesenchymal stem/stromal cell (MSC) therapies have entered clinical trials but show efficacy comparable only to autografts, reflecting the absence of lineage-matched, biologically functional scaffolds. BioMand addresses this unmet need by developing bioinspired mandibular constructs integrating advanced biomaterials, mechanobiology, and neurovascularisation. Unlike the commonly used bone marrow MSCs of mesodermal origin, dental pulp stem cells (DPSCs) are derived from the cranial neural crest (CNC), the embryonic lineage that forms craniofacial bones and peripheral nerves. Their developmental origin makes them uniquely suited for mandibular regeneration and for coupling osteogenesis with neurovascularisation. The project pursues three objectives: (i) design and fabrication of 3D-printable mandibular scaffolds with shareable CAD files and PCL-nHA constructs, (ii) establishment of mechanically induced osteogenesis of DPSCs in bioreactors without chemical supplements, and (iii) development of a multicellular neurovascularised mandibular bone model as a human-relevant preclinical platform. This will provide the first comprehensive demonstration of mechanically induced 3D osteogenesis in lineage-matched craniofacial stem cells and establish a reproducibility benchmark for craniofacial bone biofabrication through open protocols and interoperable datasets. The fellowship will provide the researcher with technical training in biofabrication and advanced cell culture, as well as transferable skills guided by ISO 9001:2015-certified quality management system implemented at AO Research Institute Davos (ARI).