Modelling arterial wall drug concentrations following the insertion of a drug-eluting stent

A mathematical model of a drug-eluting stent is proposed. The model considers a polymer region, containing the drug initially, and a porous region consisting of smooth muscle cells embedded in an extracellular matrix. An analytical solution is obtained for the drug concentration both in the target cells and the interstitial region of the tissue in terms of the drug release concentration at the interface between the polymer and the tissue. When the polymer region and the tissue region are considered as a coupled system it can be shown, under certain assumptions, that the drug release concentration satisfies a Volterra integral equation which must be solved numerically in general. The drug concentrations, both in the cellular and extracellular regions, are then determined from the solution of this integral equation and used in deriving the mass of drug in the cells and extracellular space

Zein-based smart coatings for drug-eluting stents: investigations via static and microfluidic approaches

Coronary heart disease is currently responsible for a significant percentage of global mortality in developed and developing nations alike. This occurrence takes place despite the advancement in medical technology and improved treatment options, such as stenting procedures. Due to complications with restenosis and stent thrombosis that are associated with current commercial stents, there has been a growing interest in stent research and development in order to eradicate the causes of such clinical events. The selection of an antioxidant, non-thrombogenic coating has been a major obstacle to the development of drug-eluting stents (DES), and, to date, a truly biocompatible stent platform remains elusive. Moreover, there is a need to assess stent coatings within an in vitro platform prior to in vivo and clinical studies in order to minimize adverse effects. Even if considerable progress has been made over the last two decades in the development of flow chambers to monitor and study thrombus formation outside of the circulation, blood-material interactions are still little investigated under static and dynamic modes. In order to avoid some of the drawbacks of synthetic polymers, such as their undesirable degradation products, long-lasting presence, or potential biocompatibility issues, the aim of this PhD thesis was to investigate zein as a green and abundant plant-derived protein as a coating material for DES applications. This study aimed to understand the potential uses of zein as a controlled release matrix for drug delivery systems, in addition to developing a microfluidic platform to assess the behavior and hemocompatibility of the proposed plant-based stent coatings under flow conditions

Modeling Stented Coronary Arteries: Where We are, Where to Go

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Three-dimensional printing as a cutting-edge, versatile and personalizable vascular stent manufacturing procedure:Toward tailor-made medical devices

Vascular stents (VS) have revolutionized the treatment of cardiovascular diseases, as evidenced by the fact that the implantation of VS in coronary artery disease (CAD) patients has become a routine, easily approachable surgical intervention for the treatment of stenosed blood vessels. Despite the evolution of VS throughout the years, more efficient approaches are still required to address the medical and scientific challenges, especially when it comes to peripheral artery disease (PAD). In this regard, three-dimensional (3D) printing is envisaged as a promising alternative to upgrade VS by optimizing the shape, dimensions and stent backbone (crucial for optimal mechanical properties), making them customizable for each patient and each stenosed lesion. Moreover, the combination of 3D printing with other methods could also upgrade the final device. This review focuses on the most recent studies using 3D printing techniques to produce VS, both by itself and in combination with other techniques. The final aim is to provide an overview of the possibilities and limitations of 3D printing in the manufacturing of VS. Furthermore, the current situation of CAD and PAD pathologies is also addressed, thus highlighting the main weaknesses of the already existing VS and identifying research gaps, possible market niches and future directions.This work was funded by the Basque Country Government/Eusko Jaurlaritza (Department of Education, University and Research, Consolidated Groups IT448- 22) . Sandra Ruiz-Alonso and Fouad Al -Hakim thank the Basque Country Government for the granted fellowships PRE_2021_2_0153 and PRE_2021_2_0181, respectively. Denis Scaini gratefully acknowledges support from IKERBASQUE, the Basque Foundation of Science

Mechanoresponsive drug delivery: harnessing forces for controlled release

Mechanically-activated delivery systems harness existing physiological and/or externally-applied forces to provide spatiotemporal control over the release of active agents. The presence and necessity of these forces in the human body and in the increasing use of mechanically-driven medical devices (e.g., stents, balloon catheters, gastric bands, tissue expanders) can serve as functional dynamic triggers. Therefore, this dissertation investigates the use of applied tensile strain and cyclic loading to control release of entrapped agents, and further translates the concept towards clinical applications by integrating the system with commercial medical devices that provide precise forces to trigger release. As an initial proof-of-concept, mechanoresponsive composites, consisting of highly-textured superhydrophobic barrier coatings over a hydrophilic substrate, are fabricated. The release of entrapped agents, controlled by the magnitude of applied strain, results in a graded response due to water infiltration through propagating patterned cracks in the coating. The strain-dependent delivery of anticancer agents with in vitro efficacy as well as the ex vivo delivery to esophageal tissue with an integrated stent system are demonstrated. Release is further modulated by barrier coating properties. Thicker coatings afford slower release rates with preserved in vitro activity for both a chemotherapeutic and an enzyme. Localizing coating crack patterns based on different geometric stress concentration factors further controls the selective sequential release of multiple agents. Finally, the development of a reversible mechanoresponsive system is investigated to provide cycle-mediated pulsatile release. Optimization of mechanical parameters results in delivery of multiple doses. To translate this concept towards the clinic, the system is integrated with commercial balloon catheters to provide multidose delivery of small molecules to ex vivo vessels. Using the inherent inflation and deflation of the catheter to trigger release, the system enhances existing capabilities to treat cardiovascular and peripheral artery diseases. In summary, the development of mechanoresponsive systems that respond to tensile strain and cycle number are described for the delivery of a wide-range of active agents (hydrophilic and hydrophobic small molecules as well as an enzyme), and their integration with existing medical devices. Furthermore, the comprehensive range of specific kinetic profiles, including triggered release, pulsatile delivery, and the sequential delivery of multiple agents, showcases the capabilities and versatility of these dynamic mechanoresponsive systems to modulate release for the treatment of various clinical diseases.2019-02-20T00:00:00

Urinary Stents

This open access book provides a concise overview of a range of aspects related to urinary stents. Sections within the work cover clinical and recent technological advancements in the field. Chapters feature detailed coverage of the different surgical, pharmacological and palliative treatments currently available. Insight is also given on current limitations of urinary stents and how these can be overcome by utilizing anti-biofilm coatings; new biomaterials, drug-eluting stents, and biodegradable stents. Therefore, enabling the reader to systematically gain a detailed understanding of the subject. Urinary Stents is a practical, multi-disciplinary focused resource on the complications and applications of ureteral, urethral and prostatic stents in day-to-day clinical practice. A vital read for all medical professionals and researchers who work in this area

Finite element and mechanobiological modelling of vascular devices

There are two main surgical treatments for vascular diseases, (i) percutaneous stent deployment and (ii) replacement of an atherosclerotic artery with a vascular graft or tissue engineered blood vessel. The aim of this thesis was to develop computational models that could assist in the design of vascular stents and tissue engineered vascular grafts and scaffolds. In this context, finite element (FE) models of stent expansion in idealised and patient specific models of atherosclerotic arteries were developed. Different modelling strategies were investigated and an optimal modelling approach was identified which minimised computational cost without compromising accuracy. Numerical models of thin and thick strut stents were developed using this modelling approach to replicate the ISAR-STEREO clinical trial and the models identified arterial stresses as a suitable measure of stent induced vascular injury. In terms of evaluating vascular graft performance, mechanical characterisation experiments can be conducted in order to develop constitutive models that can be used in FE models of vascular grafts to predict their mechanical behaviour in-situ. In this context, bacterial cellulose (BC), a novel biomaterial, was mechanically characterised and a constitutive model was developed to describe its mechanical response. In addition, the interaction of smooth muscle cells with BC was studied using cell culture experiments. The constitutive model developed for BC was used as an input for a novel multi-scale mechanobiological modelling framework. The mechanobiological model was developed by coupling an FE model of a vascular scaffold and a lattice free agent based model of cell growth dynamics and remodelling in vascular scaffolds. By comparison with published in-vivo and in-vitro works, the model was found to successfully capture the key characteristics of vascular remodelling. It can therefore be used as a predictive tool for the growth and remodelling of vascular scaffolds and graft

Nanoparticles: Potential for Use to Prevent Infections

One of the major issues related to medical devices and especially urinary stents are infections caused by different strains of bacteria and fungi, mainly in light of the recent rise in microbial resistance to existing antibiotics. Lately, it has been shown that nanomaterials could be superior alternatives to conventional antibiotics. Generally, nanoparticles are used for many applications in the biomedical field primarily due to the ability to adjust and control their physicochemical properties as well as their great reactivity due to the large surface-to-volume ratio. This has led to the formation of a new research field called nanomedicine which can be defined as the use of nanotechnology and nanomaterials in diagnostics, imaging, observing, prevention, control, and treatment of diseases. For example, coverings or coatings based on nanomaterials are now seen as a promising strategy for preventing or treating biofilms formation on healthcare kits, implants, and medical devices. Toxicity, inappropriate delivery, or degradation of conventionally used drugs for the treatment of infections may be avoided by using nanoparticles without or with encapsulated/immobilized active substances. Most of the materials which are used and examined for the preparation of the nanoparticles with encapsulated/immobilized active substances or smart reactive nanomaterials with antimicrobial effects are polymers, naturally derived antimicrobials, metal-based and non-metallic materials. This chapter provides an overview of the current state and future perspectives of the nanoparticle-based systems based on these materials for prevention, control, or elimination of biofilm-related infections on urinary stents. It also addresses manufacturing conditions indicating the huge potential for the improvement of existing and development of new promising stent solutions