Metal Ion-Loaded Nanofibre Matrices for Calcification Inhibition in Polyurethane Implants

Abstract

Pathologic calcification leads to structural deterioration of implant materials via stiffening, stress cracking, and other structural disintegration mechanisms, and the effect can be critical for implants intended for long-term or permanent implantation. This study demonstrates the potential of using specific metal ions (MI)s for inhibiting pathological calcification in polyurethane (PU) implants. The hypothesis of using MIs as anti-calcification agents was based on the natural calcium-antagonist role of Mg2+ ions in human body, and the anti-calcification effect of Fe3+ ions in bio-prosthetic heart valves has previously been confirmed. In vitro calcification results indicated that a protective covering mesh of MI-doped PU can prevent calcification by preventing hydroxyapatite crystal growth. However, microstructure and mechanical characterisation revealed oxidative degradation effects from Fe3+ ions on the mechanical properties of the PU matrix. Therefore, from both a mechanical and anti-calcification effects point of view, Mg2+ ions are more promising candidates than Fe3+ ions. The in vitro MI release experiments demonstrated that PU microphase separation and the structural design of PU-MI matrices were important determinants of release kinetics. Increased phase separation in doped PU assisted in consistent long-term release of dissolved MIs from both hard and soft segments of the PU. The use of a composite-sandwich mesh design prevented an initial burst release which improved the late (>20 days) release rate of MIs from the matrix.

Degradation and stabilization of polyurethane elastomers

“…Mg 2+ and Fe 3+ were shown to be able to inhibit pathological calcification in PU implants [533], with calcification also being overcome by blending a PU with silk fibroin [534].…”

Prosthetic vascular grafts engineered to combat calcification: Progress and future directions

“…For example, Singh and Wang explored metal ions as an anticalcification agent in PU implants in in vitro study using metal ion-loaded nanofiber matrices to inhibit calcification. The inclusion of either Fe 3+ or Mg 2+ ions in the PU mesh significantly inhibited calcification depositions after calcium solution incubation for 60 days compared to the unloaded PU mesh control sample (Singh & Wang, 2017). Iron citrate is another compound that can protect against calcification.…”

A critical review of fibrous polyurethane-based vascular tissue engineering scaffolds

“…The high calcification capacity of PEtUs was previously reported [ 131 ]. The presence of metal ions such as Mg 2+ and Fe 3+ [ 132 ] and silk fibroin [ 133 ] could reduce the calcification rate. Ether-free, physically cross-linked, fully aliphatic, and polybutadiene-based PUU was resistant to calcification [ 134 ].…”