Ajay Padsalgikar

In vitro oxidation of high polydimethylsiloxane content biomedical polyurethanes: correlation with the microstructure.

The resistance to in vitro metal ion oxidation of a polydimethylsiloxane (PDMS)-containing thermoplastic polyurethane elastomer (Elast-Eon) is compared with that of a polyurethane consisting of the same hard segment chemistry and content, but with aliphatic polycarbonate soft segments (PCU). Scanning electron microscopy and attenuated total reflectance Fourier transform infrared spectroscopy were used to assess changes in surface morphology and chemistry. The extent of bulk degradation was assessed indirectly by dynamic mechanical analysis and small-angle X-ray scattering experiments. The findings indicate that Elast-Eon is more resistant to oxidation than the PCU, because of the presence of the PDMS soft segments as well as its phase separated microstructure. The PCU exhibits a rather high degree of intermixing between hard and soft segments, rendering the hard segments dissolved or trapped in the soft phase more susceptible to oxidative conditions. By contrast, we propose that the existence of a completely phase separated PDMS soft phase in Elast-Eon protects the remainder of the segments from oxidation.

Limitations of predicting in vivo biostability of multiphase polyurethane elastomers using temperature-accelerated degradation testing

Polyurethane biostability has been the subject of intense research since the failure of polyether polyurethane pacemaker leads in the 1980s. Accelerated in vitro testing has been used to isolate degradation mechanisms and predict clinical performance of biomaterials. However, validation that in vitro methods reproduce in vivo degradation is critical to the selection of appropriate tests. High temperature has been proposed as a method to accelerate degradation. However, correlation of such data to in vivo performance is poor for polyurethanes due to the impact of temperature on microstructure. In this study, we characterize the lack of correlation between hydrolytic degradation predicted using a high temperature aging model of a polydimethylsiloxane-based polyurethane and its in vivo performance. Most notably, the predicted molecular weight and tensile property changes from the accelerated aging study did not correlate with clinical explants subjected to human biological stresses in real time through 5 years. Further, DMTA, ATR-FTIR, and SAXS experiments on samples aged for 2 weeks in PBS indicated greater phase separation in samples aged at 85°C compared to those aged at 37°C and unaged controls. These results confirm that microstructural changes occur at high temperatures that do not occur at in vivo temperatures. In addition, water absorption studies demonstrated that water saturation levels increased significantly with temperature. This study highlights that the multiphase morphology of polyurethane precludes the use of temperature accelerated biodegradation for the prediction of clinical performance and provides critical information in designing appropriate in vitro tests for this class of materials.

Polydimethylsiloxane-Based Polyurethanes: Phase-Separated Morphology and In Vitro Oxidative Biostability

Three series of segmented polyurethane block copolymers were synthesized using 4,4′-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BDO) or 1,3-bis(4-hydroxybutyl)tetramethyl disiloxane (BHTD) as the hard segments, and soft segments composed of poly(dimethyl siloxane) (PDMS)-based and poly(hexamethylene oxide) (PHMO) macrodiols. Copolymers synthesized with the PDMS macrodiol and PDMS and PHMO macrodiol mixtures consist of three microphases: a PDMS phase, hard domains, and a mixed phase of PHMO (when present), PDMS ether end-group segments and some dissolved hard segments. Degrees of phase separation were characterized using small-angle X-ray scattering by applying a pseudo two-phase model, and the morphology resulting from unlike segment demixing was found to be closely related to the in vitro oxidative biostability of these segmented polyurethanes.

The biostability of cardiac lead insulation materials as assessed from long-term human implants.

Accelerated in vitro biostability studies are useful for making relativistic comparisons between materials. However, no in vitro study can completely replicate the complex biochemical and biomechanical environment that a material experiences in the human body. To overcome this limitation, three insulation materials [Optim™ insulation (OPT), Pellethane® 55D (P55D), and silicone elastomer] from cardiac leads that were clinically implanted for up to five years were characterized using visual inspection, SEM, ATR-FTIR, GPC, and tensile testing. Surface cracking was not observed in OPT or silicone samples. Shallow cracking was observed in 17/41 (41%) explanted P55D samples. ATR-FTIR indicated minor surface oxidation in some OPT and P55D samples. OPT molecular weight decreased modestly (∼20%) at 2-3 years before stabilizing at 4-5 years. OPT tensile strength decreased modestly (∼25%) at 2-3 years before stabilizing at 4-5 years. OPT elongation at 4-5 years was unchanged from controls. P55D had no significant changes in molecular weight or tensile properties. Overall, results for OPT and P55D were consistent with and limited to cosmetic surface oxidation. Silicone demonstrated excellent biostability with no identifiable degradation. This study of explanted cardiac leads revealed that OPT, P55D, and silicone elastomer demonstrate similar and excellent biostability through five years of implantation in human patients.

Novel Hard-Block Polyurethanes with High Strength and Transparency for Biomedical Applications

Novel hard-block-only polyurethanes are prepared from 1,4-butanediol (BDO) and a pre-polymer synthesized separately from 1,3-bis (4-hydroxybutyl) tetramethyl disiloxane (BHTD) and 4,4′-diphenylmethane diisocyanate (MDI). Three (co)polymers using different proportions of these chain extenders were synthesized using reaction injection moulding, and their microstructure, mechanical properties and in vitro oxidative biostability were evaluated. These materials were found to form a single-phase system, and exhibit optical transparency, high elastic modulus and tensile strength, as well as significant in vitro oxidative biostability. By controlling the BDO/BHTD composition, the ductility can be tuned over orders of magnitude. These polyurethanes may be potentially suitable for biomedical applications, like electronic headers for defibrillators, pacemakers and neurostimulators, and orthopedic nail encapsulation.

Environmental stress cracking performance of polyether and PDMS‐based polyurethanes in an in vitro oxidation model

Environmental stress cracking (ESC) was replicated in vitro on Optim™ (OPT) insulation, a polydimethylsiloxane-based polyurethane utilized clinically in cardiac leads, using a Zhao-type oxidation model. OPT performance was compared to that of two industry standard polyether urethanes: Pellethane® 80A (P80A), and Pellethane® 55D (P55D). Clinically relevant specimen configurations and strain states were utilized: low-voltage cardiac lead segments were held in a U-shape by placing them inside of vials. To study whether aging conditions impacted ESC formation, half of the samples were subjected to a pretreatment in human plasma for 7 days at 37°C; all samples were then aged in oxidative solutions containing 0.9% NaCl, 20% H2 O2 , and either 0 or 0.1M CoCl2 , with or without glass wool for 72 days at 37°C. Visual and SEM inspection revealed significant surface cracking consistent with ESC on all P80A and P55D samples. Sixteen of twenty P80A and 10/20 P55D samples also exhibited breaches. Seven of 20 OPT samples exhibited shallow surface cracking consistent with ESC. ATR-FTIR confirmed surface changes consistent with oxidation for all materials. The number average molecular weight decreased an average of 31% for OPT, 86% for P80A, and 56% for P55D samples. OPT outperformed P80A and P55D in this Zhao-type in vitro ESC model. An aging solution of 0.9% NaCl, 20% H2 O2 , and 0.1M CoCl2 , with glass wool provided the best combination of ESC replication and ease of use.