Abstract:
Background: There has been a major burden in diseases associated with critical bone defects. Despite many techniques for defect management has come into use, the common treatment remains controversial. Mollusk nacre is a natural structure with outstanding mechanical property due to its notable “brick-and-mortar” architecture. Combining inorganic brick with organic mortar, natural nacre displays remarkable tensile strength and fracture toughness. Rare elements have exhibited extraordinary promotive capacities in various aspects of physiological process. Cerium ions have been reported with prospective capacities in promoting bone regeneration in many studies. Herein, inspired by the nacre architecture, our team designed and fabricated a nacre-mimetic cerium-doped layered nano-hydroxyapatite/chitosan layered composite scaffold (CeHA/CS). The scaffold displayed a distinct layered HA/CS composite structure with intervals ranging from 50 to 200 μm, which provided compatible environments for the adhesion and proliferation of human bone marrow mesenchymal stem cells (hBMSCs), allowed the in situ growth of newly formed bone tissues. In vitro, The CeHA/CS layered composite scaffolds noticeably promoted the osteogenic process through the upregulated expressions of osteogenesis-related genes like RUNX2, and COL1 by the BMP-2/P-Smad1/5 signal pathway. And simultaneously, the layered scaffolds inhibited osteoclast differentiation evidenced by the reduced TRAP positive osteoclasts and lowered bone resorption. In vivo, calvarial defected rats revealed that the layered CeHA/CS scaffolds remarkably accelerated bone regeneration at the defect site and immunofluorescence suggested the layered CeHA/CS scaffolds lowered RANKL/OPG ratio. Our results showed that CeHA/CS scaffolds may become a promising platform for bone regeneration in critical defect management by promoting osteogenesis and inhibiting osteoclast activation.
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