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.
Various
kinds of biodegradable Mg alloys have been developed in
recent years due to their appropriate mechanical properties, biodegradation,
and good biocompatibility. In this study, Mg–2.0Zn–xGd alloys (x = 0.5, 1.0, 1.5, and 2.0
wt %) were prepared. Hot extrusion was applied in order to refine
the microstructure and improve the degradation resistance. The microstructure,
mechanical properties, and in vitro degradation behavior of Mg–2.0Zn–xGd alloys were investigated first. The as-extruded Mg–2.0Zn–1.0Gd
alloy exhibits excellent mechanical properties (UTS 338 MPa, YS 284
MPa, elongation 24%) and low in vitro degradation rate (0.24 mm/year)
with uniform degradation morphology, and then, this alloy was selected
for further assessments. The cytotoxicity of as-extruded Mg–2.0Zn–1.0Gd
alloy to MC3T3-E1 cell is found to be grade 0–1, indicating
good biocompatibility. The in vivo experiment shows that the in vivo
degradation rate of this alloy is about 0.31 mm/y after 30 days implantation
in cranial defect of Sprague–Dawley rats. All of these indicate
a promising prospect of Mg–2.0Zn–1.0Gd alloy as biodegradable
applications, especially as orthopedic implants.
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