Surface immobilization of MEPE peptide onto HA/ß-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/beta-tricalcium phosphate (HA/beta-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/beta-TCP particles. The free-hydroxyl groups on the surface of the HA/beta-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/beta-TCP was confirmed. Implantation of the MEPE peptide-immobilized HA/beta-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/beta-TCP. Moreover, tartrate-resistant acid phosphatase-positive osteoclasts were observed in regenerated bone by the MEPE peptide-immobilized HA/beta-TCP, indicating that the bones newly formed by the MEPE peptide-immobilized HA/beta-TCP are actively remodeled by osteoclasts. Therefore, our data demonstrate that MEPE peptide immobilization onto the HA/beta-TCP surface stimulates bone regeneration associated with physiological bone remodeling. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.