Biological stability of polyurethane modified with covalent attachment of di‐tert‐butyl‐phenol

Abstract

Polyurethane cardiovascular implants are subject to oxidation initiated surface degradation, which is mediated by monocyte-derived macrophages (MDM); this often leads to surface cracking and device failure. The present studies examined the hypothesis that covalently attaching antioxidant, di-tert-butylphenol (DBP), to the urethane nitrogens of a polyether polyurethane (PU) via bromo-alkylation reactions could prevent this problem. PU was configured with two dosages of DBP, 0.14 mM DBP/g PU of DBP (PU-DBP) and a more highly modified (HM) 0.40 mM DBP/g PU (PU-DBP-HM). THP-1 cells, a human MDM cell line, stimulated with phorbol ester and seeded on PU, PU-DBP, and PU-DBP-HM films were assessed for reactive oxygen species (ROS) production via a fluorescent based dihydrorhodamine-123 assay. Results from these studies showed a significant dose-dependent reduction of ROS levels for THP-1 cells seeded on PU-DBP versus unmodified PU. PU, PU-DBP, or PU-DBP-HM films were implanted into subdermal pouches of Sprague-Dawley rats. Films were explanted after 10 weeks and assessed for oxidative degradation via light and scanning electron microscopy (SEM) and Fourier transformation infrared spectroscopy (FTIR). Light microscopy showed extensive surface cracking, which was confirmed via SEM, on unmodified PU surfaces that was absent in both PU-DBP and PU-DBP-HM explanted films. FTIR analysis showed reduction in oxidation-induced ether crosslinking that was directly related to DBP dosages. It is concluded that modifying PU with the covalent attachment of an antioxidant confers biodegradation resistance in vivo in a dose dependent manner; this effect is likely due to quenching of the ROS generated by the adherent macrophages.

The effect of CD47 modified polymer surfaces on inflammatory cell attachment and activation

“…FTIR analysis has shown that the oxidation of polyurethane elastomers corresponds with an increase in peak intensity at the 1174 cm −1 , assigned to the ʋ(C-O-C) of branched ether, which has been identified as a marker of oxidative degradation [14, 18, 19, 26]. The extent of ether cross-linking is quantitatively determined by normalizing the 1174 cm −1 spectral peak intensity with the peak intensity of the 1590 cm −1 spectral peak, which corresponds to a non-oxidized aromatic ring [14, 18, 19, 26]. Shown in Figure 6B (Spectra shown in Supplemental Data Figure 5), the immobilization of either hCD47 or bCD47 significantly reduced the cross-linking of the polyurethane’s ether groups.…”

“…Male Sprague Dawley rats, weighing between 300 and 350 grams were used for subdermal implant studies as previously described [18]. Rats were anesthetized with isoflurane and administered Flunixamine post surgery for analgesia.…”

“…Explanted PU films were processed for FTIR as previously described [18]. Briefly, explanted films were washed in a 1% Triton X-100 in PBS solution followed by a second series of washes in PBS.…”

“…All spectra were obtained under identical conditions from 200 scans collected at a resolution of 2 cm −1 , at a 45° angle of incidence and the atmospheric water vapor and carbon dioxide were accounted for by subtracting the appropriate reference spectrum using the Omnic software package. Deconvoluted peak measurements were acquired for the 1174 cm −1 peak and normalized to the measured 1590 cm −1 peak heights [14, 18, 19]. …”

The use of CD47-modified biomaterials to mitigate the immune response

“…[83][84][85][86] With respect to pacemaker leads, which commonly use polyurethane insulation, the duration from implantation to device failure has been shown to be as short as $2.5 years. 87 Laboratories, including our own, have tried to address the issue of oxidative degradation of polyurethane by coblending 84 or covalently linking 86,88 phenol-based antioxidants to polyurethane preparations. The limitations of this approach lie primarily in the fact that the antioxidants are expended once they react with hydroxy radicals.…”