Effects of heterogeneous surface characteristics on hemocompatibility and cytocompatibility of bacterial nanocellulose.

The surface properties of cardiovascular biomaterials play a critical role in their biological responses. Although bacterial nanocellulose (BNC) materials have exhibited potential applications in cardiovascular implants, the impact of their surface characteristics on biocompatibility has rarely been studied. This study investigated the mechanism for the biocompatibility induced by the physicochemical properties of both sides of BNC. With greater wettability and smoothness, the upper BNC surface reduced protein adsorption by 25 % compared with the lower surface. This prolonged the plasma re-calcification time by 14 % in venous blood. Further, compared with the lower BNC surface, the upper BNC surface prolonged the activated partial thromboplastin time by 5 % and 4 % in arterial and venous blood, respectively. Moreover, the lower BNC surface with lesser rigidity, higher roughness, and sparser fiber structure promoted cell adhesion. The lower BNC surface enhanced the proliferation rate of L929 and HUVECs cells by 15 % and 13 %, respectively, compared with the upper BNC surface. With lesser stiffness, the lower BNC surface upregulated the expressions of CD31 and eNOS while down-regulating the ICAM-1 expression - This promoted the proliferation of HUVECs. The findings of this study will provide valuable insights into the design of blood contact materials and cardiovascular implants.

[Thoughts on the Biological Evaluation of Biodegradable Cardiovascular Implants].

In recent years, new degradable materials have been applied to cardiovascular implants. Cardiovascular implants with different physicochemical properties and degradation properties have special endpoints for their biological evaluation. In this study, the end points of biological evaluation of degradable cardiovascular implants were reviewed by taking vascular stents and occluders as examples.

Effects of semiquinone-rich surface on the behaviors of vascular cells.

Dopamine has been widely used for surface modification of cardiovascular medical devices as it forms films on most substrates that provide functional groups for surface chemical modification. However, under oxidative stress, the phenolic hydroxyl group on dopamine can undergo reversible transformation into phenol-semiquinone-quinone, which can cause cytotoxicity and immunotoxicity. In this study, we measured the effects of semiquinone on the behavior of vascular wall cells and inflammatory cells under oxidative stress via ultraviolet irradiation with a hydrogen peroxide diluent. Na2S2O3 was used as a stabilizer to obtain a semiquinone-rich poly-dopamine film, then phenol-semiquinone-quinone ratio on its surface was evaluated at three irradiation-oxidation time points. We found that the poly-dopamine film with ultraviolet irradiation in hydrogen peroxide solution for 15 min had the highest semiquinone occupancy of 19.18%. In the experimental group irradiated for 15 min, endothelial cells were cultured statically for 3 days and the number of surface adherent endothelial cells in the group with added semiquinone stabilizer was reduced to 73% of that in the group without stabilizer, indicating that semiquinone rich surface inhibits adhesion and proliferation of endothelial cells; Smooth muscle cells were cultured statically for 3 days, and the number of adherent smooth muscle on surfaces without stabilizer was reduced to 75% of that on surfaces with stabilizer added, indicating that semiquinone rich surfaces promote smooth muscle proliferation. These results demonstrate that semiquinone can adversely affect the repair effect after implantation of cardiovascular materials. Therefore, our study provides a reference for the application and optimization of dopamine in cardiovascular implant materials.

Inflammation-triggered dual release of nitroxide radical and growth factor from heparin mimicking hydrogel-tissue composite as cardiovascular implants for anti-coagulation, endothelialization, anti-inflammation, and anti-calcification.

Cardiovascular implants made from heterogeneous tissues (HT) often clinically face premature failures such as thrombosis, inflammation, and calcification. Herein, we report a hydrogel-tissue composite exhibiting inflammation instructive release of multiple components towards preventing coagulation, promoting endothelial growth, and modulating reactive oxygen species (ROS) homeostasis. The hydrogel composed of MMP-responsive segment-crosslinked heparin mimicking polymer was loaded with a nitroxide radical via ROS cleavable boronic ester bonds and vascular endothelial growth factor (VEGF) via electrostatic attraction. Matrix metalloproteinase (MMP), which reportedly showed elevated expression in inflammation response to foreign implant degraded the hydrogel and led to the release of heparin mimicking polymer and VEGF, enhancing its anti-coagulation capacity and accelerating the growth of endothelial cells on it. In addition, the composite could sense oxidation biosignal present in the inflammation environment and subsequently release a ROS scavenger for auto-regulation of ROS balance. Subcutaneous implantation in mice suggested that the composite could steer the immune response toward an anti-inflammation state and subcutaneous implantation in rats suggested an anti-calcification effect of it. The enhanced hemocompatibility and endothelialization effects in vivo were further confirmed by the endovascular implantation of tissues via membrane-covered stent delivery. The current findings demonstrate that the incorporation of functional hydrogel into the tissue sophistically exploiting host response for controlled release of multiple active cargos is a feasible approach to boost the anticoagulant, endothelialization, anti-inflammatory, and anti-calcification functions of HT-based cardiovascular implants.

Bacteriophage therapy as a treatment option for complex cardiovascular implant infection: The German Heart Center Berlin experience.

Conventional antimicrobials have low or no activity against multidrug-resistant or chronic implant-associated infections. Lytic bacteriophages can rapidly and selectively kill bacteria, and can be combined with antibiotics. However, clinical experience of bacteriophage therapy in patients with cardiovascular infections is limited. We documented the outcome and safety of intravenous and local adjunctive bacteriophage therapy, to treat chronic relapsing cardiovascular implant infections at our institution.

2006 to 2019 Story; percutaneously implantable aortic valve prototypes.

AIMS: A review was conducted on the composition, advantages and limitations of available aortic valve prototypes to create an ideal valve for percutaneous implantation. Patients Patients with multiple comorbidities who cannot withstand the risks of open cardiac surgery. METHODOLOGY: The search was performed using online databases and textbooks. Articles were excluded based on specific criterion. RESULTS: Ten prototypes created between 2006 and 2019 were found and reviewed. The prototypes had a set of advantages and limitations with their characteristics coinciding at times. CONCLUSIONS: The ideal percutaneously implantable aortic valve should have minimum coaptation height, zero folds in the leaflets, minimum valve height, minimum leaflet flexion and three leaflets. It can be composed of biological or synthetic material, as long as it provides minimal risk of thrombosis. However, more studies are needed to ensure other ideal parameters.

Clinical and procedural implications of congenital vena cava anomalies in adults: A systematic review.

BACKGROUND: Although congenital vena cava (CVC) anomalies in adults have implications for surgical and radiological interventions, the literature is scare and disparate. The aim of this systematic review was to assess cardiovascular clinical and procedural implications of CVC anomalies in adults without congenital heart disease. METHODS AND RESULTS: We searched PubMed and EMBASE from database conception through October 2018 for English-language studies describing the epidemiology of CVC anomalies or their clinical or procedural implications in humans. Two independent reviewers screened 7093 records and identified 16 relevant studies. We found two major implications of CVC anomalies: 1) congenital inferior vena cava (CIVC) anomalies are associated with a 50-100-fold higher risk of deep venous thrombosis, particularly among younger patients, and 2) persistent left superior vena cava (PLSVC) is associated with a 2-3-fold higher risk of supraventricular arrhythmias. PLSVC also poses technical challenges to cardiovascular electronic device implantation, requiring alterations in surgical approach and lengthening procedure and X-ray exposure times. Due to the large disparity in reported prevalence rates of CIVC anomalies, we performed a meta-analysis of CIVC anomaly prevalence including 8 studies, which showed a weighted prevalence of 6.8% (95% CI, 4.5-9.2%). CONCLUSION: These findings challenge the notion that CVC anomalies are rare and asymptomatic in adults. Rather, the literature indicates that CVC anomalies are not uncommon and have important clinical and procedural implications. To further understand the prevalence and implications of CVC anomalies, a robust US population-based study and nationwide registry is warranted in the current era of venous interventions.

One step bulk modification of poly(L-lactic acid) composites with functional additives to improve mechanical and biological properties for cardiovascular implant applications.

Poly(L-lactic acid) (PLLA) has been widely used as a promising biomaterial in biomedical applications due to its biodegradability and high mechanical strength. However, because of the inherent brittleness, low impact resistance, and weak thermal stability of PLLA, the modification process is usually required to utilize it for biomedical devices. Furthermore, acidic byproducts resulting from the hydrolysis of PLLA after implantation reduce the pH of the surrounding environment and cause inflammatory responses in the implanted area, leading to the failure of their clinical applications. To this end, here, we demonstrate a novel modification process for the PLLA composite with various functional additives, such as cis-aconitic anhydride (AA), triacetin (TA), isosorbide derivative (ISB), and/or Pluronic® F127 (F). The modified PLLA composite with TA and F (PLLA/TF) showed significantly improved elongation at break and Young's modulus and retained tensile strength. Moreover, incorporating magnesium hydroxide (MH) nanoparticles (PLLA/TFMH) significantly reduced acid-induced inflammation responses caused by the acidic degradation products of PLLA. Reduced plasma protein adsorption was observed in the PLLA/TFMH. These results suggest that the one step bulk modification of biodegradable PLLA using TA, F, and MH will have great potential in cardiovascular implant applications.

Construction and application of service quality evaluation system in the preclinical research on cardiovascular implant devices.

BACKGROUND: Services for the preclinical development and evaluation of cardiovascular implant devices (CVIDs) is a new industry. However, there is still no indicator system for quality evaluation. Our aim is to construct a service for quality evaluation system for the preclinical research and development of CVIDs based on Fuzzy Analytical Hierarchy Process (FAHP). METHODS: First, we reviewed the related literature to identify and select possible factors. Second, we developed an analytic hierarchy process framework. Third, we developed a questionnaire based on pairwise comparisons and invited 10 experienced specialists to rate these factors. We then used FAHP to compute the weights of these factors and prioritize them. Finally, to demonstrate the effectiveness of the proposed indicator system, a case study was performed as a practical example. RESULTS: Four main indicators (professionalism, functionality, stability and security) and 15 subindicators were selected to form the service evaluation system based on literature review and expert's proposals. According to the weight calculation data, the order of primary indicators by importance, is professionalism (0.6457), security (0.1193), functionality (0.0958) and stability (0.0596) in sequence. Top five secondary indices are personnel's technical ability, facility and equipment attractiveness, data auditability, confidentiality capability and professional service procedures. In the case study, FW's final actual effectiveness value was 0.9076, which is the same as the actual situation. CONCLUSION: The indicator system established in this study is comprehensive, reasonable, reliable and with strong practicality. It is worth popularizing and applying. The implementation of this evaluation system can provide measurable evidence for service demander and a way to improve service quality for suppliers.

Adaptation of cardiovascular system stent implants.

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.

Investigating Regional Variation of Cardiac Implantable Electrical Device Implant Rates in European Healthcare Systems: What Drives Differences?

Despite established efficacy for cardiac implantable electrical devices (CIEDs), large differences in CIED implant rates have been documented across and within countries. The aim of this paper is to investigate the influence of socio-economic, epidemiological and supply side factors on CIED implant rates across 57 Regions in 5 EU countries and to assess the feasibility of using administrative data for this purpose. A total of 1 330 098 hospitalizations for CIED procedures extracted from hospital discharge databases in Austria, England, Germany, Italy and Slovenia from 2008 to 2012 was used in the analysis. Higher levels of tertiary education among the labour force and percent of aged population are positively associated with implant rates of CIED. Regional per capita GDP and number of implanting centres appear to have no significant effect. Institutional factors are shown to be important for the diffusion of CIED. Wide variation in CIED implant rates across and within five EU countries is undeniable. However, regional factors play a limited part in explaining these differences with few exceptions. Administrative databases are a valuable source of data for investigating the diffusion of medical technologies, while the choice of appropriate modelling strategy is crucial in identifying the drivers for variation across countries. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.

Adhesion and activation of platelets from subjects with coronary artery disease and apparently healthy individuals on biomaterials.

On the basis of the clinical studies in patients with coronary artery disease (CAD) presenting an increased percentage of activated platelets, we hypothesized that hemocompatibility testing utilizing platelets from healthy individuals may result in an underestimation of the materials' thrombogenicity. Therefore, we investigated the interaction of polymer-based biomaterials with platelets from CAD patients in comparison to platelets from apparently healthy individuals. In vitro static thrombogenicity tests revealed that adherent platelet densities and total platelet covered areas were significantly increased for the low (polydimethylsiloxane, PDMS) and medium (Collagen) thrombogenic surfaces in the CAD group compared to the healthy subjects group. The area per single platelet-indicating the spreading and activation of the platelets-was markedly increased on PDMS treated with PRP from CAD subjects. This could not be observed for collagen or polytetrafluoroethylene (PTFE). For the latter material, platelet adhesion and surface coverage did not differ between the two groups. Irrespective of the substrate, the variability of these parameters was increased for CAD patients compared to healthy subjects. This indicates a higher reactivity of platelets from CAD patients compared to the healthy individuals. Our results revealed, for the first time, that utilizing platelets from apparently healthy donors bears the risk of underestimating the thrombogenicity of polymer-based biomaterials.