Targeting Local Osteogenic and Ancillary Cells by Mechanobiologically Optimized Magnesium Scaffolds for Orbital Bone Reconstruction in Canines

Large-sized orbital
bone defects have serious consequences that destroy orbital integrity
and result in maxillofacial deformities and vision loss. The treatment
of orbital bone defects is currently palliative and not reparative,
suggesting an urgent demand for biomaterials that regenerate orbital
bones. In this study, via alloying, extrusion and surface modification,
we developed mechanobiologically optimized magnesium (Mg) scaffolds
(Ca–P-coated Mg–Zn–Gd scaffolds, referred to
as Ca–P–Mg) for the orthotopic reconstruction of large-sized
orbital bone defects. At 6 months after transplanting the scaffolds
to a clinically relevant canine large animal model, large-sized defects
were successfully bridged by an abundance of new bone with normal
mechanical properties that corresponded to gradual degradation of
the implants. The osteogenic and ancillary cells, including vascular
endothelial cells and trigeminal neurons, played important roles in
this process. The scaffolds robustly enhanced bone marrow mesenchymal
stem cell (BMSC) osteogenic differentiation. In addition, the increased
angiogenesis including increased ratio of the specific endothelial
subtype CD31hi endomucinhi (CD31hiEmcnhi) endothelial cells can facilitate osteogenesis.
Furthermore, the scaffolds trigger trigeminal neurons via transient
receptor potential vanilloid subtype 1 (Trpv1) to produce the neuropeptide
calcitonin gene-related peptide (CGRP), which promotes angiogenesis
and osteogenesis. Overall, our investigations revealed the efficacy
of Ca–P–Mg scaffolds in healing orbital bone defects
and warrant further exploration of these scaffolds for clinical applications.