Preparation of a nanoemulsion containing active ingredients of cannabis extract and its application for glioblastoma: in vitro and in vivo studies.

Recently, the anti-tumor effects of cannabis extract on various cancers have attracted the attention of researchers. Here, we report a nanoemulsion (NE) composition designed to enhance the delivery of two active components in cannabis extracts (∆9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)) in an animal model of glioblastoma. The efficacy of the NE containing the two drugs (NED) was compared with the bulk drugs and carrier (NE without the drugs) using the C6 tumor model in rats. Hemocompatibility factors (RBC, MCV, MCH, MCHC, RDW, PPP, PT and PTT) were studied to determine the potential in vivo toxicity of NED. The optimized NED with mean ± SD diameter 29 ± 6 nm was obtained. It was shown that by administering the drugs in the form of NED, the hemocompatibility increased. Cytotoxicity studies indicated that the NE without the active components (i.e. mixture of surfactants and oil) was the most cytotoxic group, while the bulk group had no toxicity. From the in vivo MRI and survival studies, the NED group had maximum efficacy (with ~4 times smaller tumor volume on day 7 of treatment, compared with the control. Also, survival time of the control, bulk drug, NE and NED were 9, 4, 12.5 and 51 days, respectively) with no important adverse effects. In conclusion, the NE containing cannabis extract could be introduced as an effective treatment in reducing brain glioblastoma tumor progression.

Limited cellular uptake of liposomes: Might thiolated phospholipids hold the key?

AIM: It was the aim of this study to evaluate the impact of surface thiolation on cellular uptake of liposomes. METHODS: Liposomes were prepared via the thin lipid film method, incorporating cholesterol, dipalmitoylphosphatidylcholin (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol). The characterization of liposomes included size, polydispersity index, surface morphology, zeta potential and stability in simulated gastric and intestinal fluid. Hemocompatibility and cytotoxicity of liposomes were investigated. Cellular uptake studies were performed on Caco-2, HeLa, HEK and SW620 cells, involving both quantitative analysis through flow cytometry and qualitative evaluation via confocal microscopy. Additionally, we investigated the impact of an oxidizing agent on thiol-dependent uptake. RESULTS: Non-thiolated and thiolated liposomes exhibited a size of 149 nm to 274 nm and a PDI between 0.3 and 0.45. Liposomes were stable in simulated intestinal and gastric fluid. Hemocompatibility studies and cytocompatibility studies of liposomes showed negligible toxic effects of liposomes. Cellular uptake of thiolated liposomes was 1.8-, 2.1-, 5.4- and 1.4-fold enhanced in comparison to non-thiolated liposomes on Caco-2, HEK, HELA and SW620 cells, respectively. The results were qualitatively verified by confocal microscopy. Thiol dependent uptake was influenced by oxidizing agents on HeLa cells. CONCLUSION: Surface thiolation represents a promising approach to enhance cellular uptake of liposomes.

Characterization and Hemocompatibility of α, ß, and γ Cyclodextrin-Modified Magnetic Nano-Adsorbents.

Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can be chemically modified to enhance toxin capture and the ability to be easily collected from the blood using an external magnetic field. Cyclodextrins (CDs) present a chemical structure that facilitates the binding of small molecules. However, the hemocompatibility of MNPs modified with films composed of different native types of CDs (α, ß, or γ) has not yet been investigated, which is information crucial to the potential clinical application of MNPs to supplement hemodialysis. To this end, films of α-, ß-, or γ-CDs were formed on MNPs and characterized. The impact of these films on the adsorbed protein structure, composition of key adsorbed proteins, and clotting kinetics were evaluated. It was found that modified MNPs did not significantly affect the secondary structure of some proteins (albumin, lysozyme, α-lactalbumin). The adsorbed proteome from platelet-poor human plasma was evaluated as a function of film properties. Compared to non-modified nanoparticles, CD-modified MNPs exhibited a significant decrease in the adsorbed protein per surface area of MNPs. The immunoblot results showed variations in the adsorption levels of C3, fibrinogen, antithrombin, Factor XI, and plasminogen across CD-modified MNPs. The hemocompatibility experiments showed that CD-modified MNPs are compatible with human whole blood, with no significant impact on platelet activation, hemolysis, or hemostasis.

Development and characterization of PLA nanocomposites reinforced with bio-ceramic particles for orthognathic implants: Enhanced mechanical and biological properties.

The clinical application of osteofixation materials is crucial for maxillofacial reconstruction and orthognathic surgeries. To overcome the limitations of traditional metallic implants, bioabsorbable materials are gaining popularity due to their ability to avoid secondary removal surgeries and reduce stress shielding. This study investigates third-generation biomaterials, focusing on polylactic acid (PLA) for its biocompatibility and biodegradability, and hydroxyapatite (HAP) for its bioactive osteoconductive and bioresorbable properties. Eggshell nanoparticles (ES-NP), HAP, and bioinert alumina particles coated with titanium dioxide (TiO2@Al2O3) were prepared using ball milling, co-precipitation, and sol-gel methods, respectively. PLA-based nanocomposites PLA/ESNP/Al2O3 (PEA), PLA/HAP/Al2O3 (PHA), PLA/ESNP/TiO2@Al2O3 (PEAT), and PLA/HAP/TiO2@Al2O3 (PHAT) were fabricated via solvent casting. Characterization techniques including X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), and Field-Emission Scanning Electron Microscopy (FE-SEM) were used to analyze the developed nanoparticles and composites. Results indicated PEAT and PHAT composites exhibited tensile strengths of 33.59 ±â€¯0.38 MPa and 32.46 ±â€¯0.46 MPa, tensile moduli of 1756.17 ±â€¯95.43 MPa and 2367.21 ±â€¯158.84 MPa, and shore d hardness values of 84.10 ±â€¯1.45 SHN and 78.00 ±â€¯2.25 SHN, respectively. Both composites achieved a wettability angle of ~65° and surface roughness below 2.19 µm, enhancing osteoblast adhesion. Additionally, MG63 cell viability was approximately 80 %, and hemolysis rates were below 2.17 %, demonstrating their potential for maxillofacial implant applications.

Anatomical compatibility of a novel total artificial heart-An in-silico study.

BACKGROUND: ShuttlePump is a novel total artificial heart (TAH) recently introduced to potentially overcome the limitations associated with the current state-of-the-art mechanical circulatory support devices intended for adults. In this study, we adapted the outflow cannulation of the previously established ShuttlePump TAH and evaluated the anatomical compatibility using the virtual implantation technique. METHODS: We retrospectively assessed the anatomical compatibility of the ShuttlePump using virtual implantation techniques within 3D-reconstructed anatomies of adult heart failure patients. Additionally, we examined the impact of outflow cannula modification on the hemocompatibility of the ShuttlePump through computational fluid dynamic simulations. RESULTS: A successful virtual implantation in 9/11 patients was achieved. However, in 2 patients, pump interaction with the thoracic cage was observed and considered unsuccessful virtual implantation. A strong correlation (r <-0.78) observed between the measured anatomical parameters and the ShuttlePump volume exceeding pericardium highlights the importance of these measurements apart from body surface area. The numerical simulation revealed that the angled outflow cannulation resulted in a maximum pressure drop of 1.8 mmHg higher than that of the straight outflow cannulation. With comparable hemolysis index, the shear stress thresholds of angled outflow differ marginally (<5%) from the established pump model. Similar washout behavior between the pump models indicate that the curvature did not introduce stagnation zone. CONCLUSION: This study demonstrates the anatomic compatibility of the ShuttlePump in patients with biventricular failure, which was achieved by optimizing the outflow cannulation without compromising hemocompatibility. Nevertheless, clinical validation is critical to ensure the clinical applicability of these findings.

Hydroxyapatite synthesis and characterization from marine sources: A comparative study.

Background: Hydroxyapatite (HAP) is a biocompatible material widely used in biomedical applications. Recent studies have explored various marine sources for HAP synthesis, demonstrating its potential for diverse applications. Objective: This study aims to compare the characteristics of hydroxyapatite synthesized from sea shells and fish bones, specifically from the shells of Scylla olivacea (orange mud crab) and bones of Eleutheronema tetradactylum (fourfinger threadfin). Materials & methods: HAP was synthesized from Scylla olivacea shells and Eleutheronema tetradactylum bones. The synthesized HAP underwent comprehensive characterization, including scanning electron microscopy (SEM) for structural analysis, hemocompatibility testing, antibacterial assays, and energy-dispersive X-ray spectroscopy (EDS) analysis. Results: SEM revealed a complex structure of HAP with a clustered arrangement and biofilm-like features. HAP derived from crab shells exhibited superior structural properties compared to that from fish bones. Both sources demonstrated good hemocompatibility, essential for biomedical applications. The antibacterial assays indicated effective antibacterial properties for both HAP sources, with crab shell-derived HAP showing slightly better performance. EDS analysis confirmed the presence of key elements necessary for HAP, with a consistent composition in both sources. Conclusion: Our study concludes that hydroxyapatite derived from Scylla olivacea shells exhibits superior properties compared to that from Eleutheronema tetradactylum bones. This research establishes a precedent for future investigations into other marine species, thereby broadening the scope and potential of hydroxyapatite synthesis from natural sources.

Simulation-based assessment of zwitterionic pendant group variations on the hemocompatibility of polyethersulfone membranes.

In the realm of hemodialysis, Polyethersulfone (PES) membranes dominate due to their exceptional stability and mechanical properties, capturing 93% of the market. Despite their widespread usage, the hydrophobic nature of PES introduces complications in hemodialysis, potentially leading to severe adverse reactions in patients with end-stage renal disease (ESRD) through protein fouling. Addressing this issue, our study focused on enhancing hemocompatibility by modifying PES surfaces with zwitterionic materials, known for their hydrophilicity and biological membrane compatibility. We investigated the functionalization of PES membranes utilizing various zwitterions in different ratios. Utilizing molecular docking, we examined the interactions of three zwitterionic ligands-carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl) phosphorylcholine (MPC)-with human serum proteins. Our analysis revealed that a 1:1 ratio of phosphobetaine and sulfobetaine exhibits the lowest affinity energy towards serum proteins, denoting an optimal hemocompatibility without the limitations associated with increased zwitterion ratios. This pivotal finding offers a new pathway for developing more efficient and safer hemodialysis membranes, promising improved care for ESRD patients. Supplementary information: The online version contains supplementary material available at 10.1186/s42252-024-00062-6.

Endothelium-Mimicking Materials: A "Rising Star" for Antithrombosis.

The advancement of antithrombotic materials has significantly mitigated the thrombosis issue in clinical applications involving various medical implants. Extensive research has been dedicated over the past few decades to developing blood-contacting materials with complete resistance to thrombosis. However, despite these advancements, the risk of thrombosis and other complications persists when these materials are implanted in the human body. Consequently, the modification and enhancement of antithrombotic materials remain pivotal in 21st-century hemocompatibility studies. Previous research indicates that the healthy endothelial cells (ECs) layer is uniquely compatible with blood. Inspired by bionics, scientists have initiated the development of materials that emulate the hemocompatible properties of ECs by replicating their diverse antithrombotic mechanisms. This review elucidates the antithrombotic mechanisms of ECs and examines the endothelium-mimicking materials developed through single, dual-functional and multifunctional strategies, focusing on nitric oxide release, fibrinolytic function, glycosaminoglycan modification, and surface topography modification. These materials have demonstrated outstanding antithrombotic performance. Finally, the review outlines potential future research directions in this dynamic field, aiming to advance the development of antithrombotic materials.

Molecular Biomarkers for In Vitro Thrombogenicity Assessment of Medical Device Materials.

To develop standardized in vitro thrombogenicity test methods for evaluating medical device materials, three platelet activation biomarkers, beta-thromboglobulin (ß-TG), platelet factor 4 (PF4), soluble p-selectin (CD62P), and a plasma coagulation marker, thrombin-antithrombin complex (TAT), were investigated. Whole blood, drawn from six healthy human volunteers into Anticoagulant Citrate Dextrose Solution A was recalcified and heparinized over a concentration range of 0.5-1.5 U/mL. The blood was incubated with test materials with different thrombogenic potentials for 60 min at 37°C, using a 6 cm2/mL material surface area to blood volume ratio. After incubation, the blood platelet count was measured before centrifuging the blood to prepare platelet-poor plasma (PPP) and platelet-free plasma (PFP) for enzyme-linked immunosorbent assay analysis of the biomarkers. The results show that all four markers effectively differentiated the materials with different thrombogenic potentials at heparin concentrations from 1.0 to 1.5 U/mL. When a donor-specific heparin concentration (determined by activated clotting time) was used, the markers were able to differentiate materials consistently for blood from all the donors. Additionally, using PFP instead of PPP further improved the test method's ability to differentiate the thrombogenic materials from the negative control for ß-TG and TAT. Moreover, the platelet activation markers were able to detect reversible platelet activation induced by adenosine diphosphate (ADP). In summary, all three platelet activation markers (ß-TG, PF4, and CD62P) can distinguish thrombogenic potentials of different materials and detect ADP-induced reversible platelet activation. Test consistency and sensitivity can be enhanced by using a donor-specific heparin concentration and PFP. The same test conditions are applicable to the measurement of coagulation marker TAT.

A Self-Skin Permeable Doxorubicin Loaded Nanogel Composite as a Transdermal Device for Breast Cancer Therapy.

Modern drug delivery research focuses on developing biodegradable nanopolymer systems. The present study proposed a polymer-based composite nanogel as a transdermal drug delivery system for the pH-responsive targeted and controlled delivery of anticancer drug doxorubicin (DOX). Nanogels have properties of both hydrogels and nanomaterials. The ß-cyclodextrin-based nanogels can enhance the loading capacity of poorly soluble drugs and promote a sustained drug release. The ß-cyclodextrin-grafted methacrylic acid conjugated hyaluronic acid composite nanogel was successfully synthesized. ß-Cyclodextrin was first grafted onto methacrylic acid. The composite nanogel-based drug carrier was prepared by controlled radical polymerization (CRP) of ß-cyclodextrin-grafted methacrylic acid with hyaluronic acid. The doxorubicin-loaded carrier was characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, zeta potential analysis, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug loading and release efficiencies were carried out at different pH levels. The maximum drug loading and encapsulation efficiencies of the synthesized final nanogel composite material at pH 8.0 were 86.44 ± 2.12 and 96.07 ± 2.01%, respectively. The DOX-loaded final material showed a 90.0 ± 2.6% release percentage of DOX at pH 5.5, whereas at pH 7.4, the release percentage of DOX was observed to be only 35.0 ± 0.3%. In vitro swelling, degradation, hemocompatibility, drug release kinetics, cytotoxicity, apoptosis, cell colocalization, skin irritation, and skin permeation studies, along with in vivo pharmacokinetic studies, were performed to prove the efficacy of the synthesized nanogel composite as a transdermal carrier for doxorubicin.

Study on the Bioactivity Response of the Newly Developed Zn-Cu-Mn/Mg Alloys for Biodegradable Implant Application.

Scaffolds play a crucial role in bone tissue engineering to support the defect area through bone regeneration and defect reconstruction. Promising tissue regeneration without negative repercussions and avoidance of the lifelong presence inside the body make bioresorbable metals prosper in the field of regenerative medicine. Recently, Zn and its alloys have emerged as promising biodegradable materials for their moderate degradation rate and satisfactory biocompatibility. Nevertheless, it is very challenging for cells to adhere and grow over the Zn surface alone, which influences the tissue-implant integration. In this study, an attempt has been made to systematically investigate the bioactivity responses in terms of in vitro hemocompatibility, cytotoxicity, antibacterial activity, and in vivo biocompatibility of newly developed Zn-2Cu-0.5Mn/Mg alloy scaffolds with different surface roughness. The rough surface of Zn-2Cu-0.5Mg shows the highest degradation rate of 0.16 mm/yr. The rough surface exhibits a prominent role in the adsorption of protein, further enhancing cell adhesion. Concentration-dependent alloy extract shows the highest cell proliferation for 12.5% of the extract with a maximum cell viability of 101% in Zn-2Cu-0.5Mn and 108% in Zn-2Cu-0.5Mg after 3 d. Acceptable hemolysis percentages (less than 5%) with promising anticoagulation properties are observed for all of the conditions. Enhanced antibacterial (Staphylococcus aureus and Escherichia coli) activity due to a significant effect of ions illustrates the maximum killing effect on the bacterial colony for the rough Zn-2Cu-0.5Mg alloy. In addition, it is observed that for rough Zn-2Cu-0.5Mn/Mg alloys, the inflammatory response is minimal after subcutaneous implantation, and neo-bone tissue forms in the defect areas of the rat femur with satisfactory biosafety response. The osseointegration property of the Zn-2Cu-0.5Mg alloy is comparable to that of the Zn-2Cu-0.5Mn alloy. Therefore, the rough surface of the Zn-2Cu-0.5Mg alloy has the potential to enhance biocompatibility and promote better osseointegration activity with host tissues for various biomedical applications.

Heparin-modified polyether ether ketone hollow fiber membrane with improved hemocompatibility and air permeability used for extracorporeal membrane oxygenation.

To expand the selection of raw material for fabricating extracorporeal membrane oxygenation (ECMO) and promote its application in lung disease therapy, polyether ether ketone hollow fiber membrane (PEEK-HFM) with designable pore characteristics, desired mechanical performances, and excellent biocompatibility was selected as the potential substitute for existing poly (4-methyl-1-pentene) hollow fiber membrane (PMP-HFM). To address the platelet adhesion and plasma leakage issues with PEEK-HFM, a natural anticoagulant heparin was grafted onto the surface using ultraviolet irradiation. Additionally, to explore the substitutability of the heparin layer while considering cost and scalability, a heparin-like layer composed of copolymers of acrylic acid and sodium p-styrenesulfonate was also constructed on the surface of PEEK-HFM Even though the successful grafting of heparin and heparin-like layers on the PEEK-HFM surface reduced the pore parameters, improvements in surface hydrophilicity also prevented the platelet-adhesion phenomenon and improved the anticoagulant behaviour, making it a viable alternative for commercial PMP-HFMs in ECMO production. Furthermore heparin-modified and heparin-like modified PEEK-HFMs demonstrated similar performance, indicating that synthetic layers can effectively replace natural heparin. This study holds practical and instructive significance for future research and the application of membranes in the development of oxygenators.

Hemocompatibility-related Adverse Events in Patients With Temporary Mechanical Circulatory Support: The Scoring Haemostasis Events and Assessment for Risk (SHEAR) Score.

Evaluation of treatment outcomes in patients supported by temporary mechanical circulatory support (tMCS) currently relies mainly on mortality, which may not sufficiently address other patient benefits or harms. Bleeding and thrombosis are major contributors to mortality. Still, current bleeding scores are not designed for critically ill patients undergoing tMCS, only consider selected populations, and do not account for the high heterogeneity among bleeding and thrombotic adverse events. To improve clinical management, a group of European experts has proposed a revised scoring system based on the MOMENTUM 3 Hemocompatibility Score and the Society of Cardiac Angiography and Interventions (SCAI)classification of cardiogenic shock. The new system termed the Scoring Haemostasis Events and Assessment for Risk (SHEAR) score, is divided into a baseline characterization stage and four escalating scoring stages encompassing all aspects of clinical relevance. This report summarizes the literature on hemocompatibility-related adverse events associated with tMCS, including bleeding, stroke, vascular access complications, hemolysis, thrombosis, and device failure. The SHEAR score provides a simple and rapid bedside scoring system aiming to provide a univocal tool to increase physician awareness of hemocompatibility complications at baseline and beyond, improve clinical research, and enable the capture of device-related complications that will inform relevant outcomes beyond mortality.

Evaluation of properties for Carbothane™ 3575A-based electrospun vascular graftsin vitroandin vivo.

Bioengineered vascular grafts (VGs) have emerged as a promising alternative to the treatment of damaged or occlusive vessels. It is thought that polyurethane (PU)-based scaffolds possess suitable hemocompatibility and biomechanics comparable to those of normal blood vessels. In this study, we investigated the properties of electrospun scaffolds comprising various blends of biostable polycarbonate-based PU (Carbothane™ 3575A) and gelatin. Scaffolds were characterized by scanning electron microscopy, infra-red spectroscopy, small-angle x-ray scattering, stress-loading tests, and interactions with primary human cells and blood. Data fromin vitroexperiments demonstrated that a scaffold produced from a blend of 5% Carbothane™ 3575A and 10% gelatin has proven to be a suitable material for fabricating a small-diameter VG. A comparativein vivostudy of such VGs and expanded polytetrafluoroethylene (ePTFE) grafts implanted in the abdominal aorta of Wistar rats was performed. The data of intravital study and histological examination indicated that Carbothane-based electrospun grafts outclass ePTFE grafts and represent a promising device for preclinical studies to satisfy vascular surgery needs.

Influence of titanium surface roughness on a nanoscale on the zeta potential and platelet adhesion.

Thromboembolic complications still arise on blood contacting surfaces. Surface charge and topography influence the subsequent deposition of proteins and platelets, potentially leading to thrombi. Research showed a correlation of surface charge and nanoscale roughness, and a negative surface charge as well as a smooth surface finish are associated with lower thrombogenicity. The aim of this study was to compare the platelet adhesion on titanium with different nanoscale roughnesses and to examine if those roughness variations caused a change in surface charge. Titanium samples were polished and roughened to four different nanoscale roughness levels. Platelet adhesion (covered surface area (CSA), N = 8) was tested in flow chambers with human whole blood using fluorescence imaging. ζ-potential was measured over a broad range of pH-values and interpolated to obtain the ζ-potential for pHBlood (7.4). Platelet adhesion tests were evaluated in terms of p-values and the Wilcoxon test effect size and the trend of the ζ-potential at pHBlood and the CSA was compared. Ra-values ranged between 35 (polished) and 156 nm. Regarding platelet adhesion, the polished sample showed the lowest mean CSA with a medium or strong effect size compared to the roughened samples. The interpolated ζ-potentials for pHBlood follow a similar trend as the CSA, with the lowest ζ-potential measured for the polished surface. These findings suggest that the decreasing ζ-potential due to lower nanoscale roughness might be an additional explanation for the improved hemocompatibility besides the smoother topography.

Production of a magnetic nanocomposite for biological and hyperthermia applications based on chitosan-silk fibroin hydrogel incorporated with carbon nitride.

Hydrogels based on natural polymers have lightened the path of novel drug delivery systems, wound healing, and tissue engineering fields because they are renewable, non-toxic, biocompatible, and biodegradable. Furthermore, applying modified hydrogels can upgrade their biological activity. Herein, Chitosan (CS) was used to create a hydrogel using terephthaloyl thiourea as a cross-linker. Silk fibroin (SF) and carbon nitride (CN) were added to the hydrogel to enhance its strength and biocompatibility. Finally, CS hydrogel/SF/CN was in situ magnetized using Fe3O4 magnetic nanoparticles (MNPs) and manufactured as a nanobiocomposite for improved hyperthermia. The structural properties of the nanobiocomposite were assessed using several analytical techniques, including VSM, FTIR, TGA, EDX, XRD, and FESEM. The saturation magnetization of this magnetic nanocomposite was 23.94 emu/g. The hemolytic experiment on the nanobiocomposite resulted in ca. 98 % cell survival, with a hemolysis rate of 1.69 %. Anticancer property is confirmed by a 20.0 % reduction in cell viability of BT549 cells at 1.75 mg/mL concentration compared to 0.015 mg/mL. The nanocomposite is non-toxic to the human embryonic kidney cell line (HEK293T), indicating its potential for biomedical applications. Finally, the magnetic nanocomposite's hyperthermia behavior was examined using a specific absorption rate (SAR), achieving the highest value of 47.44 W/g at 200.0 kHz. When subjected to an alternating magnetic field, the nanobiocomposite may perform well in hyperthermia therapy. These results indicate that the magnetic nanobiocomposite has the potential to perform well in hyperthermia therapy when subjected to an alternating magnetic field.

Constructing sodium alginate/carboxymethyl chitosan coating capable of catalytically releasing NO or CO for improving the hemocompatibility and endothelialization of magnesium alloys.

Although significant progress in developing biodegradable magnesium alloy materials in cardiovascular stents has been achieved recently, they still face challenges such as rapid in vivo corrosion degradation, inferior blood compatibility, and limited re-endothelialization after the implantation. Hydrogel coating that can catalyze the liberation of gas signal molecules offers a good solution to alleviate the corrosion rate and enhance the biocompatibility of magnesium and its alloys. In this study, based on alkaline heat treatment and construction of polydopamine coating on the surface of magnesium alloy, sodium alginate/carboxymethyl chitosan (SA/CMCS) gel was simultaneously covalently grafted onto the surface to build a natural polymer hydrogel coating, and selenocystamine (SeCA) and CO release molecules (CORM-401) were respectively immobilized on the surface of the hydrogel coating to ameliorate the anticoagulant performance and accelerate endothelial cells (ECs) growth by catalyzing the release of endogenous gas signal molecules (NO or CO). The findings verified that the as-prepared hydrogel coating can catalyze the liberation of CO or NO and significantly improve the corrosion resistance of magnesium alloy. At the same time, owing to the excellent hydrophilicity of the hydrogel coating, the good anticoagulant property of sodium alginate, and the ability of CMCS to promote the ECs growth, the modified magnesium alloy could significantly improve the albumin adsorption while preventing the adsorption of fibrinogen, hence significantly augmenting the anticoagulant properties and promoting the ECs growth. Under the catalytic release of NO or CO, the released gas molecules further enhanced hemocompatibility and promoted endothelial cell (EC) growth and the expression of vascular endothelial growth factor (VEGF) and NO of ECs. Therefore, the bioactive coatings that can catalyze the release of NO or CO have potential applications in constructing surface bioactive coatings for magnesium alloy materials used for intravascular stents.

Preoperative anatomical landmarks and longitudinal HeartMate 3 pump position in X-rays: Relevance for adverse events.

BACKGROUND: Left ventricular assist device (LVAD) malposition has been linked to hemocompatibility-related adverse events (HRAEs). This study aimed to identify preoperative anatomical landmarks and postoperative pump position, associated with HRAEs during LVAD support. METHODS: Pre- and postoperative chest X-ray measures (≤14 days pre-implantation, first postoperative standing, 6, 12, 18, and 24 months post-implantation) were analyzed for their association with HRAEs over 24 months in 33 HeartMate 3 (HM3) patients (15.2% female, age 66 (9.5) years). RESULTS: HM3 patients with any HRAE showed significantly lower preoperative distances between left ventricle and thoracic outline (dLVT) (25.3 ± 10.2 mm vs. 40.3 ± 15.5 mm, p = 0.004). A ROC-derived cutoff dLVT ≤ 29.2 mm provided 85.7% sensitivity and 72.2% specificity predicting any HRAE during HM3 support (76.2% (>29.2 mm) vs. 16.7% (≤29.2 mm) freedom from HRAE, p < 0.001) and significant differences in cardiothoracic ratio (0.58 ± 0.04 vs. 0.62 ± 0.04, p = 0.045). Postoperative X-rays indicated lower pump depths in patients with ischemic strokes (9.1 ± 16.2 mm vs. 38.0 ± 18.5 mm, p = 0.007), reduced freedom from any neurological event (pump depth ≤ 28.7 mm: 45.5% vs. 94.1%, p = 0.004), and a significant correlation between pump depth and inflow cannula angle (r = 0.66, p < 0.001). Longitudinal changes were observed in heart-pump width (F(4,60) = 5.61, p < 0.001). CONCLUSION: Preoperative X-ray markers are associated with postoperative HRAE occurrence. Applying this knowledge in clinical practice may enhance risk stratification, guide therapy optimization, and improve HM3 recipient management.

Antithrombotic Strategies With Left Ventricular Assist Devices.

Long-term outcomes of patients with advanced heart failure treated with durable left ventricular assist devices (LVADs) have been augmented due to improved durability and hemocompatibility on the backbone of pump engineering enhancements. The incidence of hemocompatibility-related adverse events (pump thrombosis, stroke and nonsurgical bleeding events) are device specific and vary by type of engineered pump. A fully magnetically levitated rotor containing LVAD in concert with use of antithrombotic therapy has successfully overcome an increased risk of pump thrombosis and stroke-risk, albeit with only modest reduction in bleeding events. Modifications to antithrombotic strategies have focused on reduced-dose vitamin K antagonist use or use of direct oral anticoagulants with demonstration of safety and progress in reduction of mucosal bleeding episodes with elimination of antiplatelet agents. This review outlines the current landscape of advances in anticoagulation management in LVAD patients, highlighting the need for ongoing research and cautious application of emerging therapies and technologies.