Surface immobilization of MEPE peptide onto HA/β-TCP ceramic particles enhances bone regeneration and remodeling

Calcium phosphate ceramics have been widely used as scaffolds for bone regeneration. Here, to improve the osteogenic potential of hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) and to apply the bioactive peptide in situ, matrix extracellular phosphoglycoprotein (MEPE) peptide, which has been shown to stimulate osteoblast differentiation, was covalently and directionally immobilized on HA/β-TCP particles. The free-hydroxyl groups on the surface of the HA/β-TCP particles were sequentially conjugated with APTES, PEG-(SS)(2), and the synthetic MEPE peptide. Using FTIR and XPS, immobilization of the MEPE peptide on the HA/β-TCP was confirmed. Implantation of the MEPE peptide-immobilized HA/β-TCP into calvarial defect and subsequent analyses using a micro CT and histology showed significant bone regeneration and increased bone area (9.89-fold) as compared to that of unmodified HA/β-TCP. Moreover, tartrate-resistant acid phosphatase-positive osteoclasts were observed in regenerated bone by the MEPE peptide-immobilized HA/β-TCP, indicating that the bones newly formed by the MEPE peptide-immobilized HA/β-TCP are actively remodeled by osteoclasts. Therefore, our data demonstrate that MEPE peptide immobilization onto the HA/β-TCP surface stimulates bone regeneration associated with physiological bone remodeling.