The management of extensive bone loss remains a clinical
challenge.
Numerous studies are underway to develop a combination of biomaterials,
biomolecules, and stem cells to address this challenge. In particular,
the systemic administration of antibodies against sclerostin, a regulator
of bone formation, was recently shown to enhance the bone repair efficiency
of dense collagen hydrogels (DCHs) hosting murine dental pulp stem
cells (mDPSCs). The aim of the present study was to assess whether
these antibodies, encapsulated and released from DCHs, could promote
craniofacial bone repair by the local inhibition of sclerostin. In
vitro studies showed that antibody loading modified neither the hydrogel
structure nor the viability of seeded mDPSCs. When implanted in a
mouse calvaria critical-size bone defect, antibody-loaded DCHs showed
repair capabilities similar to those of acellular unloaded DCHs combined
with antibody injections. Importantly, the addition of mDPSCs provided
no further benefit. Altogether, the local delivery of antisclerostin
antibodies from acellular dense collagen scaffolds is highly effective
for bone repair. The drastic reduction in the required amount of antibody
compared to systemic injection should reduce the cost of the procedure,
making the strategy proposed here a promising therapeutic approach
for large bone defect repair.