Crimping-induced structural gradients explain the lasting strength of poly l-lactide bioresorbable vascular scaffolds during hydrolysis.

Biodegradable polymers open the way to treatment of heart disease using transient implants (bioresorbable vascular scaffolds, BVSs) that overcome the most serious complication associated with permanent metal stents-late stent thrombosis. Here, we address the long-standing paradox that the clinically approved BVS maintains its radial strength even after 9 mo of hydrolysis, which induces a ∼40% decrease in the poly l-lactide molecular weight (Mn). X-ray microdiffraction evidence of nonuniform hydrolysis in the scaffold reveals that regions subjected to tensile stress during crimping develop a microstructure that provides strength and resists hydrolysis. These beneficial morphological changes occur where they are needed most-where stress is localized when a radial load is placed on the scaffold. We hypothesize that the observed decrease in Mn reflects the majority of the material, which is undeformed during crimping. Thus, the global measures of degradation may be decoupled from the localized, degradation-resistant regions that confer the ability to support the artery for the first several months after implantation.

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.

Spatial distribution and temporal evolution of scattering centers by optical coherence tomography in the poly(L-lactide) backbone of a bioresorbable vascular scaffold.

BACKGROUND: Scattering centers (SC) are often observed with optical coherence tomography (OCT) in some struts of bioresorbable vascular scaffolds (BVS). These SC might be caused by crazes in the polymer during crimp-deployment (more frequent at inflection points) or by other processes, such as physiological loading or hydrolysis (eventually increasing with time). The spatial distribution and temporal evolution of SC in BVS might help to understand their meaning. METHODS AND RESULTS: Three patients were randomly selected from 12 imaged with Fourier-domain OCT at both baseline and 6 months in the ABSORB cohort B study (NCT00856856). Frame-by-frame analysis of the SC distribution was performed using spread-out vessel charts, and the results from baseline and 6 months were compared. A total of 4,328 struts were analyzed. At baseline and follow-up all SC appeared at inflection points. No significant difference was observed between baseline and 6 months in the number of SC struts (14.9 vs. 14.5%, P=0.754) or in the distribution of SC. The proportion and distribution of SC did not vary substantially among the patients analyzed. CONCLUSIONS: The SC observed in OCT imaging of the BVS are located exclusively at inflection points and do not increase with time. These findings strongly suggest that SC are caused by crazes in the polymer during crimp-deployment, ruling out any major role of hydrolysis or other time-dependent processes.

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.

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.