James P. Oberhauser

Design principles and performance of bioresorbable polymeric vascular scaffolds

AIMS Bioresorbable polymeric vascular scaffolds may spawn a fourth revolution in percutaneous coronary intervention (PCI) and a novel treatment termed vascular restoration therapy. The principal design considerations for bioresorbable scaffolds are discussed in the context of physiological behaviour using the Bioabsorbable Vascular Solutions (BVS) ABSORB Cohort B scaffold (Abbott Vascular) as an example. METHODS AND RESULTS The lifecycle of a bioresorbable scaffold is divided into three phases: (1) revascularisation; (2) restoration; and (3) resorption. In the revascularisation phase spanning the first three months after intervention, the bioresorbable scaffold should perform comparably to metallic drug-eluting stents (DES) in terms of deliverability, radial strength, recoil, and neointimal thickening. The ensuing restoration phase is characterised by gradual erosion of radial strength and a loss of structural continuity, where the time scale at which each occurs is related to the hydrolytic degradation rate of the polymer. Natural vasomotion in response to external stimuli is theoretically possible at the end of this phase. Finally, in the resorption phase, the passive implant is systematically resorbed and processed by the body. CONCLUSIONS Limited clinical data speak to the potential of bioresorbable scaffolds as a new therapy, and future studies will prove critical to inspiring a fourth revolution in PCI.

Sonorheometry: A Noncontact Method for the Dynamic Assessment of Thrombosis

Inappropriate blood coagulation plays a central role in the onset of myocardial infarction, stroke, pulmonary embolism, and other thrombotic disorders. The ability to screen for an increased propensity to clot could prevent the onset of such events by appropriately identifying those at risk and enabling prophylactic treatment. Similarly, the ability to characterize the mechanical properties of clots in vivo might improve patient outcomes by better informing treatment strategies. We have developed a technique called sonorheometry. Unlike existing methods, sonorheometry is able to assess mechanical properties of coagulation with minimal disturbance to the delicate structure of a forming thrombus. Sonorheometry uses acoustic radiation force to produce small, localized displacements within the sample. Time delay estimation is performed on returned ultrasound echoes to determine sample deformation. Mechanical modeling and parametric fitting to experimental data yield maps of mechanical properties. Sonorheometry is well suited to both in vitro and in vivo applications. A control experiment was performed to verify that sonorheometry provides mechanical characterization in agreement with that from a conventional rheometer. We also examined thrombosis in blood samples taken from four subjects. This data suggests that sonorheometry may offer a novel and valuable method for assessing the thrombogenicity of blood samples.

The response of entangled polymer solutions to step changes of shear rate: Signatures of segmental stretch?

Experiments measuring the orientation angle and birefringence in startup and double-step strain rate flows were conducted on a 3.0 wt % 8.42 × 106 molecular weight polystyrene solution in a Couette flow cell. A phase-modulated flow birefringence apparatus was used to noninvasively probe the sample. Upon startup from rest, the orientation angle undershoots its final steady-state value, as seen by earlier investigators. When the shear rate undergoes a step increase from one nonzero value to another, the amplitude of this undershoot is decreased. However, a more significant effect is a shorter time scale overshoot in the orientation angle that is highly counterintuitive in the sense that an increase of shear rate initially produces a rotation of chain segments away from the flow direction. Similarly, a step decrease in shear rate yields an initial transient rotation toward the flow direction. In both cases, the height of the peaks depends upon the magnitude of the shear rate jump, and the width of the peaks is a function of the final shear rate. The longer time transients in the startup and step increase experiments reflect an apparent change in the relaxation time for segment orientation, which we tentatively attribute to a combination of tube dilation and convective constraint release. The shorter time scale over- and undershoots in the orientation angle appear to be qualitatively explained by considering the differences in extension or contraction of segments along the polymer chain.

The nonlinear response of entangled star polymers to startup of shear flow

We consider the response of entangled four-arm polybutadiene star solutions to steady shear and to startup of steady shear in the nonlinear shear-rate regime. Data are reported both for the shear stress, measured in a cone and plate geometry using a temperature controlled ARES rheometer, and for birefringence measured in a Couette device using two-color birefringence. These data are then compared with predictions from the Mead–Larson–Doi (MLD) and Graham, Likhtman, McLeish and Milner (GLaMM) models for linear chains, but with the reptation mechanism turned off as an “ad hoc” means of accounting for the effect of the immobile branch point in these systems. The results for both models are reasonable. However, with the Milner–McLeish model for chain length fluctuations included, the MLD model gives better results at the lowest shear rates where the deep retractions of the arms are a significant contributor to chain relaxation. On the other hand, the local implementation of convective constraint release (CCR) in the GLaMM model gives better predictions for higher shear rates between the inverse reptation and inverse Rouse times, where the CCR mechanism largely obviates any contribution of the deep arm retractions to the relaxation process.We consider the response of entangled four-arm polybutadiene star solutions to steady shear and to startup of steady shear in the nonlinear shear-rate regime. Data are reported both for the shear stress, measured in a cone and plate geometry using a temperature controlled ARES rheometer, and for birefringence measured in a Couette device using two-color birefringence. These data are then compared with predictions from the Mead–Larson–Doi (MLD) and Graham, Likhtman, McLeish and Milner (GLaMM) models for linear chains, but with the reptation mechanism turned off as an “ad hoc” means of accounting for the effect of the immobile branch point in these systems. The results for both models are reasonable. However, with the Milner–McLeish model for chain length fluctuations included, the MLD model gives better results at the lowest shear rates where the deep retractions of the arms are a significant contributor to chain relaxation. On the other hand, the local implementation of convective constraint release (CCR)...

Assessment of Material By-Product Fate from Bioresorbable Vascular Scaffolds

Fully bioresorbable vascular scaffolds (BVS) are attractive platforms for the treatment of ischemic artery disease owing to their intrinsic ability to uncage the treated vessel after the initial scaffolding phase, thereby allowing for the physiological conditioning that is essential to cellular function and vessel healing. Although scaffold erosion confers distinct advantages over permanent endovascular devices, high transient by-product concentrations within the arterial wall could induce inflammatory and immune responses. To better understand these risks, we developed in this study an integrated computational model that characterizes the bulk degradation and by-product fate for a representative BVS composed of poly(l-lactide) (PLLA). Parametric studies were conducted to evaluate the relative impact of PLLA degradation rate, arterial remodeling, and metabolic activity on the local lactic acid (LA) concentration within arterial tissue. The model predicts that both tissue remodeling and PLLA degradation kinetics jointly modulate LA fate and suggests that a synchrony of these processes could minimize transient concentrations within local tissue. Furthermore, simulations indicate that LA metabolism is a relatively poor tissue clearance mechanism compared to convective and diffusive transport processes. Mechanistic understanding of factors governing by-product fate may provide further insights on clinical outcome and facilitate development of future generation scaffolds.

Experimental studies of an entangled polystyrene solution in steady state mixed type flows

Experimental measurements of birefringence and velocity gradient components are reported for steady mixed type flows of a 0.076 g/cm3 solution of 2.89×106 MW polystyrene in a mixed toluene/oligomer solvent. The flow field is produced in a co-rotating two-roll mill with a series of different ratios of the gap width to roller radius chosen so that the flow type at the stagnation point for a Newtonian fluid would range from 0.0196⩽λ⩽0.20, where ‖E‖/‖Ω‖=(1+λ)/(1−λ). Additional data are also reported, for comparison purposes, for a similar polystyrene solution in a simple Couette flow. Finally, the stress-optical relationship is used to obtain a generalized extensional viscosity as a function of strain rate. This viscosity shows a range of strain rate thinning as predicted by reptation theory, followed at a critical Weissenberg number of 0(1) based on the Rouse relaxation time by the initial stages of a region of strain rate thickening, as predicted by the Marrucci–Grizzuti extension of reptation theory that a...

Multiplicity of morphologies in poly (l-lactide) bioresorbable vascular scaffolds

Significance Bioresorbable vascular scaffolds (BVSs) are poised to replace permanent metal stents for the treatment of coronary heart disease (CHD), which claims over 7 million lives each year. BVSs support the artery for 6 mo but completely dissolve in 2 y, eliminating serious long-term complications. The first clinically approved BVS is made from a brittle material, poly (l-lactide) (PLLA), yet it does not fracture during crimping or deployment. We used X-ray microdiffraction to discover multiple, micron-scale morphologies in the crimped BVS, which confer ductility to PLLA and resist fracture upon deployment. Contrary to intuition, the crimping process enhances scaffold strength, a result that researchers should keep in mind when designing thinner scaffolds to make BVSs broadly applicable to CHD. Poly(l-lactide) (PLLA) is the structural material of the first clinically approved bioresorbable vascular scaffold (BVS), a promising alternative to permanent metal stents for treatment of coronary heart disease. BVSs are transient implants that support the occluded artery for 6 mo and are completely resorbed in 2 y. Clinical trials of BVSs report restoration of arterial vasomotion and elimination of serious complications such as late stent thrombosis. It is remarkable that a scaffold made from PLLA, known as a brittle polymer, does not fracture when crimped onto a balloon catheter or during deployment in the artery. We used X-ray microdiffraction to discover how PLLA acquired ductile character and found that the crimping process creates localized regions of extreme anisotropy; PLLA chains in the scaffold change orientation from the hoop direction to the radial direction on micrometer-scale distances. This multiplicity of morphologies in the crimped scaffold works in tandem to enable a low-stress response during deployment, which avoids fracture of the PLLA hoops and leaves them with the strength needed to support the artery. Thus, the transformations of the semicrystalline PLLA microstructure during crimping explain the unexpected strength and ductility of the current BVS and point the way to thinner resorbable scaffolds in the future.

In vivo characterisation of bioresorbable vascular scaffold strut interfaces using optical coherence tomography with Gaussian line spread function analysis

AIMS Optical coherence tomography (OCT) of a bioresorbable vascular scaffold (BVS) produces a highly reflective signal outlining struts. This signal interferes with the measurement of strut thickness, as the boundaries cannot be accurately identified, and with the assessment of coverage, because the neointimal backscattering convolutes that of the polymer, frequently making them indistinguishable from one another. We hypothesise that Gaussian line spread functions (LSFs) can facilitate identification of strut boundaries, improving the accuracy of strut thickness measurements and coverage assessment. METHODS AND RESULTS Forty-eight randomly selected BVS struts from 12 patients in the ABSORB Cohort B clinical study and four Yucatan minipigs were analysed at baseline and follow-up (six months in humans, 28 days in pigs). Signal intensities from the raw OCT backscattering were fit to Gaussian LSFs for each interface, from which peak intensity and full-width-at-half-maximum (FWHM) were calculated. Neointimal coverage resulted in significantly different LSFs and higher FWHM values relative to uncovered struts at baseline (p<0.0001). Abluminal polymer-tissue interfaces were also significantly different between baseline and follow-up (p=0.0004 in humans, p<0.0001 in pigs). Using the location of the half-max of the LSF as the polymer-tissue boundary, the average strut thickness was 158±11 µm at baseline and 152±20 µm at six months (p=0.886), not significantly different from nominal strut thickness. CONCLUSIONS Fitting the raw OCT backscattering signal to a Gaussian LSF facilitates identification of the interfaces between BVS polymer and lumen or tissue. Such analysis enables more precise measurement of the strut thickness and an objective assessment of coverage.

The effect of free surfactant and grafted surfactant surface coverage on the rheology of organoclay dispersions

This work uses rheology to probe the solid-like network formed in organically modified montmorillonite clay dispersions. All dispersions are based upon two commercial organoclays, Cloisite® 15A and 20A, which differ only in the quantity of surfactant used in the cation exchange reaction performed to render the natural Na-montmorillonite organophilic. In both cases, the amount of surfactant used in the cation exchange reactions is in excess of the cation exchange capacity of montmorillonite. Removal of unexchanged, free surfactant and subsequent thermogravimetric analysis demonstrates that the as-received, unexchanged, and surfactant extracted organoclays possess different levels of free surfactant and grafted surfactant surface coverage. The four resulting organoclays were dispersed in p-xylene at two concentrations and subjected to oscillatory and steady shear experiments in a controlled-stress rheometer. Experimental data show that all dispersions exhibit a solid-like response at low applied stress foll...

Humidity effects in magnetic recording

Humidity effects in magnetic recording are reviewed. We highlight the progress made toward quantifying water adsorption on lubricated overcoats, leading up to the present understanding of humidity effects on magnetic recording tribology. Recently, it was found that moisture is also absorbed by hygroscopic atmospheric contaminants to form liquid nanodroplets on the overcoat. Rheological and dielectric measurements were performed to investigate the properties of the nanodroplets. Solutions of 1 wt% to 10 wt% water in Ztetraol are gel like and highly viscous. Dissolved water increases the low-frequency permittivity and conductivity, and shortens the dielectric relaxation time, relative to dry lubricant.