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Smart materials have intrinsic properties that change in a controlled fashion in response to external stimuli. Currently, the only smart materials with a significant clinical impact in cardiovascular implant design are shape memory alloys, particularly Nitinol. Recent prodigious progress in material science has resulted in the development of sophisticated shape memory polymers. In this article, we have reviewed the literature and outline the characteristics, advantages, and disadvantages of shape memory alloys and shape memory polymers which are relevant to clinical cardiovascular applications, and describe the potential of these smart materials for applications in coronary stents and transcatheter valves.

Time-consuming design and manufacturing processes are a serious disadvantage when adapting human cardiovascular implants as they cause unacceptable delays after the decision to intervene surgically has been made. An ideal cardiovascular implant should have a broad range of characteristics such as strength, viscoelasticity and blood compatibility. The present research proposes the sequence of the geometrical adaptation procedures and presents their results. The adaptation starts from the identification of a person’s current health status while performing abdominal aortic aneurysm (AAA) imaging, which is a point of departure for the mathematical model of a cardiovascular implant. The computerized tomography scan shows the patient-specific geometry parameters of AAA and helps to create a model using COMSOL Multiphysics software. The initial parameters for flow simulation are taken from the results of a patient survey. The simulation results allow choosing the available shape of an implant which ensures a non-turbulent flow. These parameters are essential for the design and manufacturing of an implant prototype which should be tested experimentally for the assurance that the mathematical model is adequate to a physical one. The article gives a focused description of competences and means that are necessary to achieve the shortest possible preparation of the adapted cardiovascular implant for the surgery.

Objectives: Cell sources for cardiovascular tissue engineering (TE) are scant. However, the need for an ideal TE cardiovascular implant persists. We investigated the cardiotomy reservoir (CR) as a potential cell source that is more accessible and less ethically problematic. Methods: CR (n = 10) were removed from the bypass system after surgery. Isolation was performed using different isolation methods: blood samples were taken from the cardiopulmonary bypass and centrifuged at low density. The venous filter screen was cut out and placed into petri dishes for cultivation. The spongelike filter was removed, washed and treated in the same way as the blood samples. After cultivation, cell lines of fibroblasts (FB) and endothelial cells (EC) were obtained for analysis. The cells were seeded on polyurethane patches and analyzed via scanning electron microscopy (SEM), Life/Dead assay and immunohistochemistry. Results: No correlation between age, time of surgery and quality of cells was observed. The successful extraction of FB and was proven by positive staining results for TE-7, CD31 and vWF. Cell morphology, cytoskeleton staining and quantification of proliferation using WST-1 assay resembled the cells of the control group in all ways. The topography of a confluent and vital cell layer after cell seeding was displayed by SEM analysis, Life/Dead Assay and immunohistochemistry. The establishment of an extracellular matrix (ECM) was proven by positive staining for collagen IV, laminin, fibronectin and elastin. Conclusions: Viable FB and EC cell lines were extracted from the CR after surgery. Easy access and high availability make this cell source destined for widespread application in cardiovascular tissue engineering.

Shear-mediated platelet activation (SMPA) is central in thrombosis of implantable cardiovascular therapeutic devices. Despite the morbidity and mortality associated with thrombosis of these devices, our understanding of mechanisms operative in SMPA, particularly in free flowing blood, remains limited. Herein we present and discuss a range of emerging mechanisms for consideration for “free flow” activation under supraphysiologic shear. Further definition and manipulation of these mechanisms will afford opportunities for novel pharmacologic and mechanical strategies to limit SMPA and enhance overall implant device safety.

In an effort to better understand current test practices and improve nonclinical testing of cardiovascular metallic implants, the Food and Drug Administration (FDA) held a public workshop on Cardiovascular Metallic Implants: corrosion, surface characterization, and nickel leaching. The following topics were discussed: (1) methods used for corrosion assessments, surface characterization techniques, and nickel leach testing of metallic cardiovascular implant devices, (2) the limitations of each of these in vitro tests in predicting in vivo performance, (3) the need, utility, and circumstances when each test should be considered, and (4) the potential testing paradigms, including acceptance criteria for each test. In addition to the above topics, best practices for these various tests were discussed, and knowledge gaps were identified. Prior to the workshop, discussants had the option to provide feedback and information on issues relating to each of the topics via a voluntary preworkshop assignment. During the workshop, the pooled responses were presented and a panel of experts discussed the results. This article summarizes the proceedings of this workshop and background information provided by workshop participants. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. J Biomed Mater Res Part B: Appl Biomater, 105B: 1330-1341, 2017.

Glass coatings are of great interest for biomedical implant application due to their excellent properties. Nowadays they are used in different fields including drug delivery, for bone tissue regeneration or as implant. Nevertheless they can only be applied using high temperatures. Therefore their usage in the field of cardiovascular implant application is still restricted. Accordingly new developments in this field have been carried out to overcome this problem and to coat cardiovascular implants. Here, novel glass-like coatings have been developed and applied using sol-gel technique at moderate temperatures. The biocompatibility and selectivity have been analyzed using human endothelial cells. The obtained results clarify that the developed compositions can either promote or suppress endothelial cell growth only by altering the sintering atmosphere. A later application as thin layer on cardiovascular implants like stents is conceivable.

Ophiopogonin D, a traditional Chinese medicinal ingredient, was immobilized to form a coating onto the surface of 316L stainless steel (316L SS), which is often used in cardiovascular implant materials, and evaluated for its endothelialization ability in vitro. The immobilized coating showed more hydrophilic property compared with the 316L SS control, contributing to protein absorption and cell spreading. A CCK-8 assay was performed to investigate the attachment and proliferation of vascular endothelial cells (VEC) onto the coating, and the results showed that there were more VEC on the Ophiopogonin D coating than on the 316L SS surface. The acridine orange (AO)/propidium iodide (PI) staining images of the VEC proved that the Ophiopogonin D coating could effectively inhibit VEC apoptosis, compared with the control. In addition, VEC on the Ophiopogonin D coating released more nitric oxide (NO) and PGI2 compared with VEC on the 316L SS. All the results indicated that Ophiopogonin D could significantly improve surface endothelialization and possessed potential applications for the surface modification of cardiovascular devices.

Owing to their success in clinical practice, the prevalence of cardiovascular implants is continuously increasing. Implant infection is a relevant complication but remains a diagnostic challenge because echocardiography as a first-line test may be limited. Accordingly, a multimodality approach is increasingly used for diagnostic workup and supported by recent guidelines. As reviewed here, computed tomography and nuclear imaging provide incremental diagnostic value and may be combined in a single hybrid imaging session using positron emission tomography/computed tomography or single photon emission computed tomography/computed tomography. Molecular or cellular imaging helps to overcome the limitations of morphological imaging in implants. Larger-scale clinical studies, earlier application in the time course of diagnosis, monitoring of therapy success, technical advances, and novel radiopharmaceuticals will all contribute to sustained growth of advanced infection-targeted imaging in cardiovascular medicine.

Many cardiovascular device alloys contain nickel, which if released in sufficient quantities, can lead to adverse health effects. However, in-vivo nickel release from implanted devices and subsequent biodistribution of nickel ions to local tissues and systemic circulation are not well understood. To address this uncertainty, we have developed a multi-scale (material, tissue, and system) biokinetic model. The model links nickel release from an implanted cardiovascular device to concentrations in peri-implant tissue, as well as in serum and urine, which can be readily monitored. The model was parameterized for a specific cardiovascular implant, nitinol septal occluders, using in-vitro nickel release test results, studies of ex-vivo uptake into heart tissue, and in-vivo and clinical measurements from the literature. Our results show that the model accurately predicts nickel concentrations in peri-implant tissue in an animal model and in serum and urine of septal occluder patients. The congruity of the model with these data suggests it may provide useful insight to establish nickel exposure limits and interpret biomonitoring data. Finally, we use the model to predict local and systemic nickel exposure due to passive release from nitinol devices produced using a wide range of manufacturing processes, as well as general relationships between release rate and exposure. These relationships suggest that peri-implant tissue and serum levels of nickel will remain below 5 μg/g and 10 μg/l, respectively, in patients who have received implanted nitinol cardiovascular devices provided the rate of nickel release per device surface area does not exceed 0.074 μg/(cm2 d) and is less than 32 μg/d in total. Statement of significance The uncertainty in whether in-vitro tests used to evaluate metal ion release from medical products are representative of clinical environments is one of the largest roadblocks to establishing the associated patient risk. We have developed and validated a multi-scale biokinetic model linking nickel release from cardiovascular devices in-vivo to both peri-implant and systemic levels. By providing clinically relevant exposure estimates, the model vastly improves the evaluation of risk posed to patients by the nickel contained within these devices. Our model is the first to address the potential for local and systemic metal ion exposure due to a medical device and can serve as a basis for future efforts aimed at other metal ions and biomedical products.

Highlights: • We examine vascular stem cell function on microgrooved and micropost patterned polymer substrates. • 10 μm microgrooved surfaces significantly lower VSC proliferation but do not modulate calcified matrix deposition. • Micropost surfaces significantly lower VSC proliferation and decrease calcified matrix deposition. - Abstract: Multipotent vascular stem cells have been implicated in vascular disease and in tissue remodeling post therapeutic intervention. Hyper-proliferation and calcified extracellular matrix deposition of VSC cause blood vessel narrowing and plaque hardening thereby increasing the risk of myocardial infarct. In this study, to optimize the surface design of vascular implants, we determined whether micropatterned polymer surfaces can modulate VSC differentiation and calcified matrix deposition. Undifferentiated rat VSC were cultured on microgrooved surfaces of varied groove widths, and on micropost surfaces. 10 μm microgrooved surfaces elongated VSC and decreased cell proliferation. However, microgrooved surfaces did not attenuate calcified extracellular matrix deposition by VSC cultured in osteogenic media conditions. In contrast, VSC cultured on micropost surfaces assumed a dendritic morphology, were significantly less proliferative, and deposited minimal calcified extracellular matrix. These results have significant implications for optimizing the design of cardiovascular implant surfaces.

In an era of increased cardiovascular disease burden in the ageing population, there is great demand for devices that come in to contact with the blood such as heart valves, stents, and bypass grafts that offer life saving treatments. Nitric oxide (NO) elution from healthy endothelial tissue that lines the vessels maintains haemostasis throughout the vasculature. Surgical devices that release NO are desirable treatment options and N-diazeniumdiolates and S-nitrosothiols are recognized as preferred donor molecules. There is a keen interest to investigate newer methods by which NO donors can be retained within biomaterials so that their release and kinetic profiles can be optimized. A range of polymeric scaffolds incorporating microparticles and nanomaterials are presenting solutions to current challenges, and have been investigated in a range of clinical applications. This review outlines the application of NO donors for cardiovascular therapy using biomaterials that release NO locally to prevent thrombosis and intimal hyperplasia (IH) and enhance endothelialization in the fabrication of next generation cardiovascular device technology.

Antibody-conjugated surfaces are being studied for cardiovascular implant applications to capture endothelial progenitor cells and promote endothelialization. However, despite the large amount of literature on endothelial progenitor cell capture efficiency, little effort has been made to understand acute blood responses to the modified surfaces. We hypothesize that CD34 antibody conjugation passivates surfaces against procoagulatory events, and thus improves hemocompatibility. To test this hypothesis, we subjected the modified films to hemocompatibility tests to evaluate contact activation, platelet adhesion and activation, as well as whole blood clotting response to the films. Here, we demonstrate the alteration of blood responses due to polyacrylic acid (PAAc) engraftment and subsequent antibody conjugation on biaxially stretched polycaprolactone (PCL) films. Compared to PCL, PAAc-engrafted PCL (PCL-PAAc) and CD34-antibody-conjugated films (PCL-PAAC-CD34) resulted in a four- to ninefold (p0.001) reduced platelet activation. PCL-PAAc, however, resulted in an increased contact activation on thromboelastography, and a poorer blood compatibility index assay (43.4% +/- 2.3% vs. 60.9% +/- 2.5%, p0.05). PCL-PAAC-CD34, on the other hand, resulted in delayed clot formation (r = 19.3 +/- 1.5, k = 6.8 +/- 0.6 min) and reduced platelet adhesion and activation, and yielded the highest blood compatibility index score, indicating least thrombogenicity (69.3% +/- 3.2%). Our results suggest that CD34 antibody conjugation significantly improved the hemocompatibility of PAAc-conjugated PCL.

Purpose: The increasing popularity of both magnetic resonance angiography and minimally invasive cardiovascular interventional procedures has led to the requirement for the development of implant devices that not only provide for patient safety, but produce minimal artifacts in diagnostic images. The purpose of this paper is to assess and discuss physical principles and ASTM testing standards related to the MRI compatibility of implanted devices. Analysis and review of imaging compatibility and safety of common implants and devices: Standard procedures are described to assess safety and ability to image near implanted stents and heart valves made from different materials and of varying geometry. MRI physical principles, material properties and MR simulations are discussed in the context of estimation of ferromagnetic force, displacement, torque, tissue heating, susceptibility artifacts, and radiofrequency shielding in cardiovascular stents and heart valves during MR imaging. Conclusion: MRI compatibility is a function of both material composition and device geometry. MR-safe devices are available that provide for reduced image artifacts over stainless-steel devices.

Regenerating failed tissue and organs through tissue engineering offers hope of treating disease and revolutionizing the practice of medicine in ways as significant as the introduction of antibiotics. However, major technological success is only one leg of the race. Commercializing technology with a viable business model in a rapidly changing healthcare system requires not just the successful development of technology but also a consideration of the investment required to scale manufacturing and meet regulatory requirements, integration within standard care delivery models, and demonstration of clinical and health economic value necessary to provide a return on investment.

In this review, surface modification of implant devices by immobilization of biological molecules is discussed. A brief introduction to the development of biomolecular surface science is presented, followed by a review of current activities in selected fields. Bone-contacting devices and some cardiovascular implant devices are reviewed as paradigmatic examples of research that is currently taking place. Advances in the basic fields of cell and tissue biology, in addition to concurrent developments in surface science tools, suggest that 'peri-implant biologics', or the control and direction of the host response at the implant-tissue interface by implant-surface-linked biomolecules, could be a major area of growth in the medical devices field in the next few years.

Cardiovascular diseases are still one of the major causes of death for the people in the world. Biomedical implantable devices are the basic approach on the treatment of cardiovascular diseases. However, unexpected and serious complications can be observed in the case of their usage. Nanotechnology gives a promising perspective to overcome these drawbacks. Nanoparticulate drug delivery systems have develop superior medical solutions and offer better prospects to patients. This review comprehensively summarizes the recent situation, the benefits and the role of nanocarriers in cardiovascular implant technology.

In the field of cardiovascular implant technology, synthetic implants, biological grafts and biohybrids are used for valves and vascular grafts. There is a great need for vascular grafts with small inner diameters and heart valve prostheses with growing potential for children. New opportunities for the design of artificial tissue structures via ice templating and electrospinning are described. Exemplarily, developments of vascular grafts, and heart valves will be presented.

Bioelectric charge transfer at the blood–wall interface may be a crucial factor affecting thrombosis on implant materials. A program of studies was conducted to determine the electrokinetic and other physical properties of a wide spectrum of materials including organic polymers, metals, inorganics, heterogeneous compounds, and animal tissue. From these tests, materials were selected for in-vivo cannulation experiments. In this manner, a search was made to find a correlation between surface charge characteristics and thrombosis on cardiovascular implant materials. It was found that materials exhibiting a substantial positive charge were prone to rapid thrombosis. No clear correlation can be stated, as yet, regarding the thrombogenecity of highly charged negative surfaces or slightly charged surfaces. However, many heterogeneous materials have exhibited prolonged in-vivo patency. It appears necessary to isolate surface effects from volumetric effects to seek the role of bioelectric charge transfer in blood thrombus formation.

Nucleation and growth of calcium phosphate crystals on blood pumps designed to assist or replace the natural heart is a limiting factor in the long-term survival of experimental animals. This phenomenon, first reported by Olsen et al. [24] in 1975, is an acknowledged problem in all cardiovascular implant centers with routine animal survival times greater than 100 days[8]. The exact cause of the deposition of calcium phosphate, crystallization, and growth is not known, but several factors have been identified as important participants in the process. These factors will be discussed in some detail below.

Bioelectric charge transfer between blood and the vascular wall appears to play a significant role in maintaining vascular homeostasis. Since the surface charge characteristics of the vessel wall are a function of the dielectric properties of the material, a study was made of the dielectric characteristics of various ion permeable materials and their relationship to electrokinetic phenomena and thrombogenicity. The dielectric properties of the ion permeable materials and of animal tissue were determined and found to be strikingly similar. Several models of electrodiffusion phenomena are reviewed with respect to dielectric properties. The electro-osmotic characteristics of animal tissue and ion permeable materials were investigated, and it was found that animal tissue exhibited electro-osmotic characteristics to a greater degree than did any other man-made materials. The propensity of a material to electro-osmose could not be predicted from the dielectric properties. In addition, no correlation could be found between thrombogenicity and dielectric properties. Dielectric relaxation phenomena is reviewed, and its possible contribution to nonthrombogenicity through the generation of a uniform, constant wall surface charge is presented. It is concluded that to mimic the ion content and mobility characteristics of animal tissue, as determined by dielectric properties, is insufficient to preclude thrombus formation.