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

Abstract

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