Fully biodegradable hierarchically designed high-performance nanocellulose piezo-arrays.

While piezoelectric sensing and energy-harvesting devices still largely rely on inorganic components, biocompatible and biodegradable piezoelectric materials, such as cellulose nanocrystals, might constitute optimal and sustainable building blocks for a variety of applications in electronics and transient implants. To this aim, however, effective methods are needed to position cellulose nanocrystals in large and high-performance architectures. Here, we report on scalable assemblies of cellulose nanocrystals in multilayered piezoelectric systems with exceptional response, for various application scopes.

Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model.

Gut microbiota affect transplantation outcomes; however, the influence of immunosuppression and cell therapy on the gut microbiota in cardiovascular care remains unexplored. We investigated gut microbiota dynamics in a nonhuman primate (NHP) cardiac ischemia/reperfusion model while under immunosuppression and receiving cell therapy with human induced pluripotent stem cell (hiPSC)-derived endothelial cells (EC) and cardiomyocytes (CM). Both immunosuppression and EC/CM co-treatment increased gut microbiota alpha diversity.

Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging.

Restricting the intake of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan in young or adult mice. However, their effects when initiated in aged animals are unknown. Here we investigate the consequences of consuming a diet with 67% reduction of all amino acids (low AA) or of isoleucine alone (low Ile), in male and female C57BL/6J.

Cardiac overexpression of a mitochondrial SUR2A splice variant impairs cardiac function and worsens myocardial ischemia reperfusion injury in female mice.

The small splice variant of the sulfonylurea receptor protein isoform 2 A (SUR2A-55) targets mitochondria and enhances mitoK activity. In male mice the overexpression of this protein promotes cardioprotection, reducing myocardial injury after an ischemic insult. However, it is unclear what impact SUR2A-55 overexpression has on the female myocardium.

Nanoparticle-mediated delivery of placental gene therapy via uterine artery catheterization in a pregnant rhesus macaque.

Nanoparticles offer promise as a mechanism to non-invasively deliver targeted placental therapeutics. Our previous studies utilizing intraplacental administration demonstrate efficient nanoparticle uptake into placental trophoblast cells and overexpression of human IGF1 (hIGF1). Nanoparticle-mediated placental overexpression of hIGF1 in small animal models of placental insufficiency and fetal growth restriction improved nutrient transport and restored fetal growth.

Nanoparticle-mediated delivery of placental gene therapy via uterine artery catheterization in a pregnant rhesus macaque.

Unlabelled: Nanoparticles offer promise as a mechanism to non-invasively deliver targeted placental therapeutics. Our previous studies utilizing intraplacental administration demonstrate efficient nanoparticle uptake into placental trophoblast cells and overexpression of human ( ). Nanoparticle-mediated placental overexpression of in small animal models of placental insufficiency and fetal growth restriction improved nutrient transport and restored fetal growth.

Differential changes in expression of inflammatory mRNA and protein after oleic acid-induced acute lung injury.

Acute Respiratory Distress syndrome (ARDS) is a clinical syndrome of noncardiac pulmonary edema and inflammation leading to acute respiratory failure. We used the oleic acid infusion pig model of ARDS resembling human disease to explore cytokine changes in white blood cells (WBC) and plasma proteins, comparing baseline to ARDS values. Nineteen juvenile female swine were included in the study.

Human iPSC-derived Committed Cardiac Progenitors Generate Cardiac Tissue Grafts in a Swine Ischemic Cardiomyopathy Model without Triggering Ventricular Arrhythmias.

Background: The adult human heart following a large myocardial infarction is unable to regenerate heart muscle and instead forms scar with the risk of progressive heart failure. Large animal studies have shown that intramyocardial injection of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) following a myocardial infarction result in cell grafts but also ventricular arrhythmias. We hypothesized that intramyocardial injection of committed cardiac progenitor cells (CCPs) derived from iPSCs, combined with cardiac fibroblast-derived extracellular matrix (cECM) to enhance cell retention will: i) form cardiomyocyte containing functional grafts, ii) be free of ventricular arrhythmias and iii) restore left ventricular contractility in a post-myocardial infarction (MI) cardiomyopathy swine model.

Indirect cardiac output assessment in a swine pediatric acute respiratory distress syndrome model.

Purpose: To investigate the correlation between volume of carbon dioxide elimination (V̇CO) and end-tidal carbon dioxide (PETCO) with cardiac output (CO) in a swine pediatric acute respiratory distress syndrome (ARDS) model.

Methods: Respiratory and hemodynamic variables were collected from twenty-six mechanically ventilated juvenile pigs under general anesthesia before and after inducing ARDS, using oleic acid infusion.

Results: Prior to ARDS induction, mean (SD) CO, V̇CO, PETCO, and dead space to tidal volume ratio (V/V) were 4.

Stretchable piezoelectric biocrystal thin films.

Stretchability is an essential property for wearable devices to match varying strains when interfacing with soft tissues or organs. While piezoelectricity has broad application potentials as tactile sensors, artificial skins, or nanogenerators, enabling tissue-comparable stretchability is a main roadblock due to the intrinsic rigidity and hardness of the crystalline phase. Here, an amino acid-based piezoelectric biocrystal thin film that offers tissue-compatible omnidirectional stretchability with unimpaired piezoelectricity is reported.

Combined Treatment of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Endothelial Cells Regenerate the Infarcted Heart in Mice and Non-Human Primates.

Background: Remuscularization of the mammalian heart can be achieved after cell transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs). However, several hurdles remain before implementation into clinical practice. Poor survival of the implanted cells is related to insufficient vascularization, and the potential for fatal arrhythmogenesis is associated with the fetal cell-like nature of immature CMs.

Biventricular Interaction During Acute Left Ventricular Ischemia in Mice: A Combined In-Vivo and In-Silico Approach.

Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation.

Disruption of the nuclear localization signal in RBM20 is causative in dilated cardiomyopathy.

Human patients carrying genetic mutations in RNA binding motif 20 (RBM20) develop a clinically aggressive dilated cardiomyopathy (DCM). Genetic mutation knockin (KI) animal models imply that altered function of the arginine-serine-rich (RS) domain is crucial for severe DCM. To test this hypothesis, we generated an RS domain deletion mouse model (Rbm20ΔRS).

Overexpression of a Short Sulfonylurea Splice Variant Increases Cardiac Glucose Uptake and Uncouples Mitochondria by Regulating ROMK Activity.

The mitochondrial splice variant of the sulfonylurea receptor (SUR2A-55) is associated with protection from myocardial ischemia-reperfusion (IR) injury, increased mitochondrial ATP sensitive K channel activity (mitoK) and altered glucose metabolism. While mitoK channels composed of CCDC51 and ABCB8 exist, the mitochondrial K pore regulated by SUR2A-55 is unknown. We explored whether SUR2A-55 regulates ROMK to form an alternate mitoK.

Finding the most suitable puncture site for intraosseous access in term and preterm neonates: an ultrasound-based anatomical pilot study.

The purpose of this prospective ultrasound-based pilot study was to identify the most suitable tibial puncture site for intraosseous (IO) access in term and preterm neonates, describe tibial dimensions at this site, and provide anatomical landmarks for rapid localization. We measured the tibial dimensions and distances to anatomical landmarks at puncture sites A (proximal: 10 mm distal to the tibial tuberosity; distal: 10 mm proximal to the malleolus medialis) and B (chosen by palpation of the pediatrician), in 40 newborns in four weight groups (< 1000 g; 1000-2000 g, 2000-3000 g, and 3000-4000 g). Sites were rejected if they fell short of the assumed safety distance to the tibial growth plate of 10 mm.

Caveolin-3 and Caveolae regulate ventricular repolarization.

Rationale: Flask-shaped invaginations of the cardiomyocyte sarcolemma called caveolae require the structural protein caveolin-3 (Cav-3) and host a variety of ion channels, transporters, and signaling molecules. Reduced Cav-3 expression has been reported in models of heart failure, and variants in CAV3 have been associated with the inherited long-QT arrhythmia syndrome. Yet, it remains unclear whether alterations in Cav-3 levels alone are sufficient to drive aberrant repolarization and increased arrhythmia risk.

Biventricular interaction during acute left ventricular ischemia in mice: a combined in-vivo and in-silico approach.

Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation.

In Vivo Longitudinal Monitoring of Cardiac Remodeling in Murine Ischemia Models With Adaptive Bayesian Regularized Cardiac Strain Imaging: Validation Against Histology.

Adaptive Bayesian regularized cardiac strain imaging (ABR-CSI) uses raw radiofrequency signals to estimate myocardial wall contractility as a surrogate measure of relative tissue elasticity incorporating regularization in the Bayesian sense. We determined the feasibility of using ABR-CSI -derived strain for in vivo longitudinal monitoring of cardiac remodeling in a murine ischemic injury model (myocardial infarction [MI] and ischemia-reperfusion [IR]) and validated the findings against ground truth histology. We randomly stratified 30 BALB/CJ mice (17 females, 13 males, median age = 10 wk) into three surgical groups (MI = 10, IR = 12, sham = 8) and imaged pre-surgery (baseline) and 1, 2, 7 and 14 d post-surgery using a pre-clinical high-frequency ultrasound system (VisualSonics Vevo 2100).

Stimuli-Responsive Polymer Coatings for the Rapid and Tunable Contact Transfer of Plasmid DNA to Soft Surfaces.

We report the design and characterization of thin polymer-based coatings that promote the contact transfer of DNA to soft surfaces under mild and physiologically relevant conditions. Past studies reveal polymer multilayers fabricated using linear poly(ethylene imine) (LPEI), poly(acrylic acid) (PAA), and plasmid DNA promote contact transfer of DNA to vascular tissue. Here, we demonstrate that changes in the structure of the polyamine building blocks of these materials can have substantial impacts on rates and extents of contact transfer.

pH-Responsive Polyelectrolyte Coatings that Enable Catheter-Mediated Transfer of DNA to the Arterial Wall in Short and Clinically Relevant Inflation Times.

We report the design and characterization of pH-responsive polymer coatings that enable catheter balloon-mediated transfer of DNA to arterial tissue in short, clinically relevant inflation times. Our approach exploits the pH-dependent ionization of poly(acrylic acid) (PAA) to promote disassembly and release of plasmid DNA from polyelectrolyte multilayers. We characterized the contact transfer of multilayers composed of PAA, plasmid DNA, and linear poly(ethyleneimine) (LPEI) identified as promising in prior studies on the delivery of DNA to arterial tissue.