Polyester urethane urea (PEUU) functionalization for enhanced anti-thrombotic performance: advancing regenerative cardiovascular devices through innovative surface modifications.

Introduction: Thrombogenesis, a major cause of implantable cardiovascular device failure, can be addressed through the use of biodegradable polymers modified with anticoagulating moieties. This study introduces a novel polyester urethane urea (PEUU) functionalized with various anti-platelet deposition molecules for enhanced antiplatelet performance in regenerative cardiovascular devices. Methods: PEUU, synthesized from poly-caprolactone, 1,4-diisocyanatobutane, and putrescine, was chemically oxidized to introduce carboxyl groups, creating PEUU-COOH. This polymer was functionalized in situ with polyethyleneimine, 4-arm polyethylene glycol, seleno-L-cystine, heparin sodium, and fondaparinux. Functionalization was confirmed using Fourier-transformed infrared spectroscopy and X-ray photoelectron spectroscopy. Bio-compatibility and hemocompatibility were validated through metabolic activity and hemolysis assays. The anti-thrombotic activity was assessed using platelet aggregation, lactate dehydrogenase activation assays, and scanning electron microscopy surface imaging. The whole-blood clotting time quantification assay was employed to evaluate anticoagulation properties. Results: Results demonstrated high biocompatibility and hemocompatibility, with the most potent anti-thrombotic activity observed on pegylated surfaces. However, seleno-L-cystine and fondaparinux exhibited no anti-platelet activity. Discussion: The findings highlight the importance of balancing various factors and addressing challenges associated with different approaches when developing innovative surface modifications for cardiovascular devices.

Cortical Thinning in High-Grade Asymptomatic Carotid Stenosis.

BACKGROUND AND PURPOSE: High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere. METHODS: We used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis-Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis. RESULTS: Among 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032). CONCLUSIONS: Our findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.

Small Diameter Cell-Free Tissue-Engineered Vascular Grafts: Biomaterials and Manufacture Techniques to Reach Suitable Mechanical Properties.

Vascular grafts (VGs) are medical devices intended to replace the function of a blood vessel. Available VGs in the market present low patency rates for small diameter applications setting the VG failure. This event arises from the inadequate response of the cells interacting with the biomaterial in the context of operative conditions generating chronic inflammation and a lack of regenerative signals where stenosis or aneurysms can occur. Tissue Engineered Vascular grafts (TEVGs) aim to induce the regeneration of the native vessel to overcome these limitations. Besides the biochemical stimuli, the biomaterial and the particular micro and macrostructure of the graft will determine the specific behavior under pulsatile pressure. The TEVG must support blood flow withstanding the exerted pressure, allowing the proper compliance required for the biomechanical stimulation needed for regeneration. Although the international standards outline the specific requirements to evaluate vascular grafts, the challenge remains in choosing the proper biomaterial and manufacturing TEVGs with good quality features to perform satisfactorily. In this review, we aim to recognize the best strategies to reach suitable mechanical properties in cell-free TEVGs according to the reported success of different approaches in clinical trials and pre-clinical trials.

Development of novel measures for Alzheimer's disease prevention trials (NoMAD).

INTRODUCTION: Assessment of cognition and everyday function is essential in clinical trials for Alzheimer's disease (AD). Two novel measures of cognition (No Practice Effects (NPE) cognitive battery and Miami Computerized Functional Assessment Scale (CFAS)) were designed to have robust psychometric properties and reduced practice and ceiling effects. This study aims to evaluate if the NPE and CFAS demonstrate stronger psychometric properties and reduced practice effects compared with established measures, including the Preclinical Alzheimer Cognitive Composite (PACC), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Functional Activities Questionnaire (FAQ). METHODS: This parallel group, four-site study will randomize 320 cognitively intact adults aged 60 to 85 years to novel or well-established measures of cognition and function. All participants will receive assessments at baseline (week 0), 3-months, and 12-months, as well as a brain MRI scan and Apolipoprotein E genetic test at study entry. Analyses will determine psychometric properties of the NPE and CFAS, compare the sensitivity of measures to AD risk markers, and identify cognitive domains within the NPE. DISCUSSION: Practice effects have been a major limitation of Alzheimer's disease clinical trials that typically assess cognitive changes over serial assessments. Detection of functional impairment in cognitively normal individuals with biomarkers for Alzheimer's disease requires instruments sensitive to very subtle functional changes. This study is intended to support the validation of two new composite measures, the NPE battery and the CFAS, which may advance clinical testing of interventions for individuals across the spectrum of early stage Alzheimer's disease. TRIAL REGISTRATION: NCT03900273.