Sclerostin\nAntibody-Loaded Dense Collagen Hydrogels\nPromote Critical-Size Bone Defect Repair

The management of extensive bone loss remains a clinical\nchallenge.\nNumerous studies are underway to develop a combination of biomaterials,\nbiomolecules, and stem cells to address this challenge. In particular,\nthe systemic administration of antibodies against sclerostin, a regulator\nof bone formation, was recently shown to enhance the bone repair efficiency\nof dense collagen hydrogels (DCHs) hosting murine dental pulp stem\ncells (mDPSCs). The aim of the present study was to assess whether\nthese antibodies, encapsulated and released from DCHs, could promote\ncraniofacial bone repair by the local inhibition of sclerostin. In\nvitro studies showed that antibody loading modified neither the hydrogel\nstructure nor the viability of seeded mDPSCs. When implanted in a\nmouse calvaria critical-size bone defect, antibody-loaded DCHs showed\nrepair capabilities similar to those of acellular unloaded DCHs combined\nwith antibody injections. Importantly, the addition of mDPSCs provided\nno further benefit. Altogether, the local delivery of antisclerostin\nantibodies from acellular dense collagen scaffolds is highly effective\nfor bone repair. The drastic reduction in the required amount of antibody\ncompared to systemic injection should reduce the cost of the procedure,\nmaking the strategy proposed here a promising therapeutic approach\nfor large bone defect repair.