Inhibition of Bioprosthesis Calcification Due to Synergistic Effect of Fe/Mg Ions to Polyethylene Glycol Grafted Bovine Pericardium

Abstract

Calcification has limited the durability of bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium (BP). The present study describes calcium antagonistic effect of polyethylene glycol grafted bovine pericardium (PEG-GABP) with Fe2+/Mg2+ delivery from a co-matrix system in rat subcutaneous model. Retrieved samples were biochemically evaluated for calcification and alkaline phosphate (AP) activity. Scanning electron micrographs of 21-day explants had shown excessive calcification with glutaraldehyde treated BP (control). However, the PEG grafting and Fe/Mg release had substantially inhibited the deposition of calcium on BP. The extractable alkaline phosphatase activity was also reduced with PEG grafting and metal ion release to BP. The extractable AP had shown peak activity at 72 h [for GATBP—250.5 ± 1.2 nm pnp/mg protein/min enzyme activity (unit), PEG-GABP—165.2 ± 16.6 units], but markedly reduced after 21 days (22.1 ± 1.8 and 12.0 ± 1.5 units, respectively). The initial high levels may be due to tissue injury via surgery, which mitigated with time. It is assumed that ferric ions may slow down or retard the calcification process by the inhibition of proper formation of hydroxy apatite while magnesium ions disrupt the growth of these crystals by replacing Ca2+. In addition it may be hypothesized that these metal ions may inhibit the key element alkaline phosphatase, which acts as the substrate for mineralization. Hence, it is conceivable that a combination therapy via surface grafting of PEG and local delivery of low levels of ferric and magnesium ions may prevent the bioprosthesis associated calcification.