Bioresorbable Polymeric Scaffold in Cardiovascular Applications.

Advances in material science and innovative medical technologies have allowed the development of less invasive interventional procedures for deploying implant devices, including scaffolds for cardiac tissue engineering. Biodegradable materials (e.g., resorbable polymers) are employed in devices that are only needed for a transient period. In the case of coronary stents, the device is only required for 6-8 months before positive remodelling takes place. Hence, biodegradable polymeric stents have been considered to promote this positive remodelling and eliminate the issue of permanent caging of the vessel. In tissue engineering, the role of the scaffold is to support favourable cell-scaffold interaction to stimulate formation of functional tissue. The ideal outcome is for the cells to produce their own extracellular matrix over time and eventually replace the implanted scaffold or tissue engineered construct. Synthetic biodegradable polymers are the favoured candidates as scaffolds, because their degradation rates can be manipulated over a broad time scale, and they may be functionalised easily. This review presents an overview of coronary heart disease, the limitations of current interventions and how biomaterials can be used to potentially circumvent these shortcomings in bioresorbable stents, vascular grafts and cardiac patches. The material specifications, type of polymers used, current progress and future challenges for each application will be discussed in this manuscript.

How does the Nature of an Excipient and an Atheroma Influence Drug-Coated Balloon Therapy?

The advent of drug-eluting stents and drug-coated balloons have significantly improved the clinical outcome of patients with vascular occlusions. However, ischemic vascular disease remains the most common cause of death worldwide. Improving the current treatment modalities demands a better understanding of the processes which govern drug uptake and retention in blood vessels. In this study, we evaluated the influence of urea and butyryl-trihexyl citrate, as excipients, on the efficacy of drug-coated balloon therapy. An integrated approach, utilizing both in-vitro and in-silico methods, was used to quantify the tracking loss, vessel adhesion, drug release, uptake, and distribution associated with the treatment. Moreover, a parametric study was used to evaluate the potential influence of different types of lesions on drug-coated balloon therapy. Despite the significantly higher tracking loss (urea: 35.5% vs. butyryl-trihexyl citrate: 8.13%) observed in the urea-based balloons, the drug uptake was almost two times greater than with its hydrophobic counterpart. Non-calcified lesions were found to delay the transmural propagation of sirolimus while calcification was shown to limit the retentive potential of lesions. Ultimately this study helps to elucidate how different excipients and types of lesions may influence the efficacy of drug-coated balloon therapy.

Assessing the influence of atherosclerosis on drug coated balloon therapy using computational modelling.

Interventional therapies such as drug-eluting stents (DES) and drug-coated balloons (DCB) have significantly improved the clinical outcomes of patients with coronary occlusions in recent years. Despite this marked improvement, ischemic cardiovascular disease remains the most common cause of death worldwide. To address this, research efforts are focused on improving the safety and efficacy of the next generation of these devices. However, current experimental methods are unable to account for the influence of atherosclerotic lesions on drug uptake and retention. Therefore, in this study, we used an integrated approach utilizing both in vitro and in silico methods to assess the performance of DCB therapy. This approach was validated against existing in vivo results before being used to numerically estimate the effect of the atheroma. A bolus release of sirolimus was observed with our coating matrix. This, coupled with the rapid saturation of specific and non-specific binding sites observed in our study, indicated that increasing the therapeutic dose coated onto the balloons might not necessarily result in greater uptake and/or retention. Additionally, our findings alluded to an optimal exposure time, dependent on the coating matrix, for the DCBs to be expanded against the vessel. Moreover, our findings suggest that a biphasic drug release profile might be beneficial for establishing and maintaining the saturation of bindings sites within severely occluded vessels. Ultimately, we have demonstrated that computational methods may be capable of assessing the efficacy of DCB therapy as well as predict the influence of atherosclerotic lesions on said efficacy.

Provisional Stenting for the Treatment of Bifurcation Lesions: In Vitro Insights.

Provisional stenting is considered the gold standard approach for most bifurcation lesions, but the benefit of routine side branch (SB) strut dilatation has not been fully elucidated. A benchtop model was used to determine the benefits of routine side branch (SB) dilatation techniques on strut apposition, acute thrombogenicity, and flow disruption. Three different provisional bifurcation techniques were compared: no SB dilatation "keep it open" method (KIO), sequential balloon dilatation (SBD), and kissing balloon inflation (KBI). Stents were deployed in a silicon bifurcation model and perfused with blood at a flow rate of 200 ml/min for 60 min. Optical coherence tomography (OCT) pullbacks were obtained before and after flow perfusion to conduct strut analysis and acute thrombus measurement respectively. Computational fluid dynamics (CFD) models were created using OCT pullbacks and simulated based on experimental conditions to analyze flow disruption. The strut analysis showed that KBI had the lowest percentage of floating (10.6 ± 2.3%) (p = 0.0004) and malapposed (41.2 ± 8.5%) struts (p = 0.59), followed by SBD and then KIO. This correlated to KBI having the lowest amount of thrombus formed at the SB, followed by SBD, with KIO being the most thrombogenic (KBI: 0.84 ± 0.22mm2, SBD: 1.17 ± 0.25mm2, KIO: 1.31 ± 0.36mm2, p = 0.18). CFD models also predicted a similar trend, with KBI having the lowest amount of area of high shear rate as well as flow recirculation. Based on this benchtop model, SB intervention strategies demonstrated a reduction in number of struts and resulting thrombogenicity at the bifurcation ostia. Graphical abstract.