Biological stability of polyurethane modified with covalent attachment of di-tert-butyl-phenol (original) (raw)
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Journal of Biomedical Materials Research Part A, 2006
Polyurethane (PU) components of cardiovascular devices are subjected to oxidation-initiated surface degradation, which leads to cracking and ultimately device failure. In the present study, we investigated a novel bromoalkylation chemical strategy to covalently attach the antioxidant, di-tert-butylphenol (DBP), and/or cholesterol (Chol) to the PU urethane nitrogen groups to hypothetically prevent oxidative degradation. These experiments compared PU, PU-DBP, PU-Chol, and PU-Chol-DBP. A series of comparative oxidative degradation studies involved exposing PU samples (modified and unmodified) to H 2 O 2 -CoCl 2 for 15 days at 37°C, to cause accelerated oxidative degradation. The extent and effects of degradation were assessed by attenuated total reflectance Fourier transformation infrared spectroscopy (FTIR), scanning electron microscopy (SEM), surface contact angle measurements, and mechanical testing. Both the Chol and DBP modification conferred signifi-cant resistance to oxidation related changes compared to unmodified PU per FTIR and SEM results. SEM demonstrated cavitation only in unmodified PU. However, contact angle analysis showed significant oxidation-induced changes only in the Chol-modified PU formulations. Most importantly, uniaxial stress-strain testing revealed that only PU-DBP demonstrated bulk elastomeric properties that were minimally affected by oxidation; PU, PU-Chol, PU-Chol-DBP showed marked deterioration of their stressstrain properties following oxidation. In conclusion, these results demonstrate that derivatizing PU with DBP confers significant resistance to oxidative degradation compared with unmodified PU.
Journal of Biomedical Materials Research Part A, 2010
Oxidative degradation of the polyurethane elastomeric (PU) components greatly reduces the efficacy of PU-containing cardiovascular devices. Covalently appending the phenol-based antioxidant, 4-substituted 2,6-di-tert-butylphenol (DBP), to PU hard segments effectively reduced oxidative degradation of the PU in vivo and in vitro in prior studies by our group. In these experiments, we analyze the contribution of the tethering molecule to the antioxidant capabilities of the DBP-modified PU. Bromoalkylation chemistry was used to link DBP to the hard segment of the polyether PU, Tecothane, via our original linker (PU-DBP) or variants containing side chains with one (PU-C-DBP) or three (PU-3C-DBP) carbons. Two additional DBP variants were fabricated in which the DBP group was appended to the alkyl chain via an oxygen atom (PU-O-DBP) or an amide linkage in the middle of the tether (PU-NHCO-DBP). All DBP variant films and unmodified control films were subject to oxidative degradation via 15-day immersion in a solution of 20% H 2 O 2 þ 0.1M CoCl 2 . At the end of the oxidation protocol, films were analyzed for the presence of oxidation-related endpoints via scanning electron microscopy, contact angle measurements, and Fourier transformation infrared spectroscopy (FTIR). All DBP-containing variants resisted oxidation damage significantly better than the unmodified control PU. SEM analysis of oxidized PU-C-DBP and PU-O-DBP showed evidence of surface cracking, consistent with oxidative degradation of the PU surfaces. Similarly, there was a trend in increased ether crosslinking, a marker for oxidative degradation, in PU-C-DBP and PU-NHCO-DBP films. Consistent with these FTIR results, both PU-C-DBP and PU-NHCO-DBP had significant reductions in measured surface hydrophobicity as a result of oxidation. These data show for the first time that the choice of linker molecule significantly affects the efficiency of the linked phenolic antioxidant. V C 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 94A: 751-759, 2010
Biomaterials, 2005
After almost half a century of use in the health field, polyurethanes (PUs) remain one of the most popular group of biomaterials applied for medical devices. Their popularity has been sustained as a direct result of their segmented block copolymeric character, which endows them with a wide range of versatility in terms of tailoring their physical properties, blood and tissue compatibility, and more recently their biodegradation character. While they became recognized in the 1970s and 1980s as the blood contacting material of choice in a wide range of cardiovascular devices their application in long-term implants fell under scrutiny with the failure of pacemaker leads and breast implant coatings containing PUs in the late 1980s. During the next decade PUs became extensively researched for their relative sensitivity to biodegradation and the desire to further understand the biological mechanisms for in vivo biodegradation. The advent of molecular biology into mainstream biomedical engineering permitted the probing of molecular pathways leading to the biodegradation of these materials. Knowledge gained throughout the 1990s has not only yielded novel PUs that contribute to the enhancement of biostability for in vivo long-term applications, but has also been translated to form a new class of bioresorbable materials with all the versatility of PUs in terms of physical properties but now with a more integrative nature in terms of biocompatibility. The current review will briefly survey the literature, which initially identified the problem of PU degradation in vivo and the subsequent studies that have led to the field's further understanding of the biological processes mediating the breakdown. An overview of research emerging on PUs sought for use in combination (drug+polymer) products and tissue regeneration applications will then be presented.
Journal of Biomedical Materials Research Part A, 2007
Although relatively resistant to oxidation, polycarbonate-based polyurethanes (PCNUs) are degraded by monocyte-derived macrophages (MDM) by a co-mediated mechanism involving both hydrolytic and oxidative pathways. Since a previous study showed that PCNU pretreatment with H 2 O 2 modulated degradation by esterases, human MDM were used to further elucidate this dual pathway mechanism of degradation for 14 C-radiolabeled PCNUs (synthesized with 1,6-hexane diisocyanate:polycarbonatediol: butanediol with different stoichiometry (HDI431 and HDI321) or another diisocyanate 4,4 0 -methylene bisphenyl diisocyanate (MDI321)). Scanning electron microscopy of PCNU slips pretreated with 20% H 2 O 2 showed that HDI431 had visible holes with more radiolabel release than from the other PCNUs. When MDM were seeded on H 2 O 2 -treated PCNUs, degradation of HDI321 and MDI321, but not HDI431 was decreased. Esterase activ-ity was inhibited in MDM on all surfaces except MDI321, whereas inhibition of acid phosphatase occurred on all surfaces. The material surface itself, induced H 2 O 2 release from live MDM, with more H 2 O 2 elicited by phorbol myristate acetate treated MDM when cultured on HDI431 but not the other materials. H 2 O 2 pretreatment affected cell function by chemically altering the material surface and MDM-mediated degradation, known to be dependent on surface chemistry. The findings highlight that both oxidative and hydrolytic mechanisms need to be understood in order to tailor material chemistry to produce desired cell responses for in vivo applications.
Recent advances in biomedical polyurethane biostability and biodegradation
Polymer International, 1998
This paper summarizes our recent e †orts to better understand the e †ects of antioxidants, the e †ects of strain-state, mechanistic studies of soft segment cleavage by reactive oxygen radicals, and the e †ects of di †erent soft segment chemistries on the biostability/biodegradation of polyether polyurethanes (PEUUs). In vivo cage implant system studies and in vitro cobalt ion/ hydrogen peroxide studies have been carried out on PEUUs and the polymers have been analysed by attenuated total reÑectance and Fourier transform infrared (ATR-FTIR) spectroscopy, and scanning electron microscopic (SEM) characterization of the PEUU surfaces. The natural antioxidant, vitamin E, has been shown to inhibit biodegradation and enhance biostability of PEUUs. Studies of the e †ect of stress state on PEUU biodegradation demonstrate that stress can inhibit biodegradation. While polyether soft segments may be cleaved by the presence of reactive oxygen radicals, the presence of oxygen has a profound e †ect in accelerating biodegradation. The biodegradation of polyurethanes may be inhibited by substituting di †erent chemistries such as polydimethylsiloxanes, polycarbonates, and hydrocarbon soft segments for the polyether soft segments. To safely utilize polyurethanes in long-term biomedical devices, the biodegradation mechanisms of polyurethane elastomers must be fully understood and subsequently prevented. 1998 SCI.
Journal of Biomedical Materials Research Part A, 2013
The resistance to oxidation and environmental stress cracking of poly(carbonate urethanes) (PCUs) has generated significant interest as potential replacements of poly(ether urethanes) in medical devices. Several in vitro models have been developed to screen segmented polyurethanes for oxidative stability. High concentrations of reactive oxygen intermediates produced by combining hydrogen peroxide and dissolved cobalt ions has frequently been used to predict long-term oxidative degradation with short-term testing. Alternatively, a 3% H 2 O 2 concentration without metal ions is suggested within the ISO 10993-13 standard to simulate physiological degradation rates. A comparative analysis which evaluates the predictive capabilities of each test method has yet to be completed. To this end, we have utilized both systems to test three commercially available PCUs with low and high soft segment content: Bionate V R PCU and Bionate V R II PCUs, two materials with different soft segment chemistries, and CarboSil V R TSPCU, a thermoplastic silicone PCU. Bulk properties of all PCUs were retained with minor changes in molecular weight and tensile properties indicating surface oxidative degradation in the accelerated system after 36 days. Soft segment loss and surface damage were comparable to previous in vivo data. The 3% H 2 O 2 method exhibited virtually no changes on the surface or in bulk properties after 12 months of treatment despite previous in vivo results. These results indicate the accelerated test method more effectively characterized the oxidative degradation profiles than the 3% H 2 O 2 treatment system. The lack of bulk degradation in the 12-month study also supports the hydrolytic stability of these PCUs. V
In vitro evaluation of the inflammatory activity of ultra-high molecular weight polyethylene
Biomaterials, 2003
To understand the inflammatory potential of oxidised ultra high molecular weight polyethylene (ox-UHMWPE) compared with the virgin one (UHMWPE), we analysed in vitro the predisposition of their interaction with plasma proteins and cells involved in the inflammatory response. The adsorption on the surface of the two materials of adhesion proteins (Fibronectin and Albumin), and pro-inflammatory proteins (IgG and IgA) have been studied. Moreover, we have evaluated the materials effect on complement activation and on macrophages and monocytes-neutrophils behaviour.
Journal of Biomedical Materials Research, 2001
Poly(ester)urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly-(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonateurea)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether)urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A 2 and cholesterol esterase; solutions of H 2 O 2 /CoCl 2 , tbutyl peroxide/CoCl 2 (t-but/CoCl 2), and glutathione/tbutyl peroxide/CoCl 2 (Glut/t-but/CoCl 2); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37°C for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl 2 , Glut/ t-but/CoCl 2 , and plasma fractions I-III. Pulse-Tec grafts exposed to the H 2 O 2 /CoCl 2 mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl 2 and Glut/t-but/CoCl 2 showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl 2 mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)urethane grafts do.
Degradation of polyurethanes in vitro and in vitro: comparison of different models
Colloids and Surfaces B: Biointerfaces, 1993
This study compares and contrasts mechanisms of polyetherurethane (PEU) degradation m vitro and in vivo. Models comprising incubation with hydrogen peroxide in vitro (H202). m vtvo subcutaneous rat implant (SUBQ). and subcutaneous rat cage implant (CAGE) are described and compared with in vivo degradation of the pacemaker lead device retrieved after human implant (PACE). Experimental results support the hypothesis that stress accelerates PEU degradation. Scanning electron microscopy (SEMI, gel permeation chromatography (GPC), and Fourier transform IR spectroscopy/attenuated total reflectance (FT-IR/ATR) evaluation of tested PEU samples suggests, for all models. decreased soft segment and increased ester functtonality at the polymer surface These observations are consistent with a single, metal ton catalyzed. polyester intermediate, oxidative degradation mechanism common to all models, and with device performance m VIVO. Model comparison suggests that m vitro H,Oz and in vivo SUBQ and CAGE models accurately mimic m vtvo degradation of the pacemaker lead device (PACE).