Surface modification of porous alpha-tricalcium phosphate granules with heparin enhanced their early osteogenic capability in a rat calvarial defect model

Heparin binds to and modulates various growth factors, potentially augmenting the bone-forming capability of biomaterials. Here, alpha-tricalcium phosphate (alpha-TCP) granules were modified with peptide containing the marine mussel-derived adhesive sequence, which reacts with alpha-TCP surface, and cationic sequence, which binds to heparin (alpha-Ph). alpha-Ph retained the alpha-TCP phase and intergranule spaces after the surface modification. The existence of heparin on alpha-Ph granules was confirmed using X-ray photoelectron spectroscopy. Granules of alpha-TCP and alpha-Ph were implanted into critical-size defects in rat calvaria for 4 weeks. Micro-computed tomography, histological evaluation, and Alcian blue staining revealed that alpha-Ph induced superior bone formation compared with alpha-TCP. Newly formed bone on alpha-Ph was preferentially in contact with the Alcian blue-stained surfaces of granules. These results suggested that heparinization enhanced the early osteogenic capacity of alpha-TCP, possibly by modulating the secretion of Alcian blue-stained extracellular matrixes.