Mechanoresponsive Hydrogels Emerging from Dynamic and Non-Covalent Interactions.

Mechanoresponsive hydrogels undergo changes in their physical and chemical properties in response to mechanical stimuli such as strain, force, or shear stress. These responses are often mediated by dynamic or non-covalent intermolecular interactions. Unlike covalent bonds, which confer desirable mechanical strength but result in static networks, dynamic crosslinking motifs introduce reversibility that enables mechanically actuatable behaviors such as self-healing, shear-thinning or -thickening, and strain-stiffening.

Long-Term Clinical Outcomes and Predictors of Mortality in Implantable Cardioverter-Defibrillator Recipients in New Zealand (ANZACS-QI 83).

Background: The long-term clinical outcomes of implantable cardioverter-defibrillator (ICD) recipients across New Zealand are unknown. This study aims to compare the all-cause mortality of primary and secondary prevention ICD recipients in New Zealand and identify predictors of mortality.

Method: Patients who received a primary or secondary prevention ICD in New Zealand between 2016 and 2020 were identified using the Aotearoa NZ All Cardiology Services Quality Improvement Cardiac Implanted Device Registry [ANZACS-QI DEVICE], a national registry for cardiac implantable electronic devices.

Electrocardiographic imaging: technical developments and future applications for non-invasive electroanatomical study of the human heart.

Electrocardiographic imaging (ECGI) is a non-invasive technique that combines patient-specific cardiac anatomy with numerous body-surface potentials to gain insight into the electrical epicardial activity across the whole heart. This review summarises some of the latest hardware developments for ECGI data acquisition as well as innovative software solutions to address the inverse problem of electrocardiography. It delves into some of the successful clinical applications of ECGI while highlighting the hurdles that still stand in the way of its more widespread roll-out to healthcare.

Programmable Host-Guest Recognition for Shape-Shifting Supramolecular Nanostructure States.

The ability to design nanostructures with programmable and reversible morphological transformations is essential for advancing supramolecular chemistry toward functional biomaterials. Here, a pH-sensitive supramolecular system is shown comprising a peptide amphiphile functionalized with carboxylate-terminated bicyclo[2.2.

Mechanistic Insights for Glucose-Driven Coacervation of a Supramolecular Peptide and Therapeutic Protein.

Biological systems leverage spontaneous and transient liquid-liquid phase separation (LLPS) of proteins and biomolecules to achieve remarkable functionality. In particular, the LLPS of intrinsically disordered proteins underpins the formation of membraneless compartments in living cells, inspiring synthetic designs based on polymers and polypeptides. While these bioinspired materials have garnered significant interest, LLPS driven by ordered supramolecular assemblies of low-molecular-weight building blocks remains less explored.

Injectable hydrogel-based drug formulation for enhancing tertiary lymphoid structure formation and cancer immunotherapy efficacy.

Tertiary lymphoid structures (TLSs) in the tumor microenvironment are associated with improved cancer prognosis and enhanced immune checkpoint blockade (ICB) responses. In this study, an injectable hydrogel-based drug formulation is developed to stimulate TLSs formation in a B16-OVA melanoma mouse model. A hydrogel, termed HA-CPP⸦CB[8], is formed by supramolecular interactions between 4-(4-chlorophenyl)pyridine modified hyaluronic acid (HA-CPP) and cucurbit[8]uril (CB[8]).

Diboronate-Modified Hyaluronic Acid for Glucose-Responsive Insulin Delivery.

Diabetes requires precise insulin management to maintain glycemic control and prevent severe complications. Glucose-responsive delivery systems envision an autonomous approach to improve insulin therapy. Here, a glucose-sensitive insulin delivery system comprising hyaluronic acid conjugated with a diboronate glucose binder as a carrier for diol-modified insulin is shown.

Supramolecular Peptide Depots for Glucose-Responsive Glucagon Delivery.

Precise blood glucose control continues to be a critical challenge in the treatment and management of type 1 diabetes in order to mitigate both acute and chronic complications. This study investigates the development of a supramolecular peptide amphiphile (PA) material functionalized with phenylboronic acid (PBA) for glucose-responsive glucagon delivery. The PA-PBA system self-assembles into nanofibrillar hydrogels in the presence of physiological glucose levels, resulting in stable hydrogels capable of releasing glucagon under hypoglycemic conditions.

Enhancing Gene Delivery to Breast Cancer with Highly Efficient siRNA Loading and pH-Responsive Small Extracellular Vesicles.

Small extracellular vesicles (sEVs) are promising nanocarriers for drug delivery to treat a wide range of diseases due to their natural origin and innate homing properties. However, suboptimal therapeutic effects, attributed to ineffective targeting, limited lysosomal escape, and insufficient delivery, remain challenges in effectively delivering therapeutic cargo. Despite advances in sEV-based drug delivery systems, conventional approaches need improvement to address low drug-loading efficiency and to develop surface functionalization techniques for precise targeting of cells of interest, all while preserving the membrane integrity of sEVs.

A Supramolecular-Quantum Dot System for Broad-Spectrum Detection of Fentanyl Analogs.

Synthetic opioids, especially fentanyl and its analogs, have created an epidemic of abuse and significantly increased overdose deaths in the United States. Current detection methods have drawbacks in their sensitivity, scalability, and portability that limit field-based application to promote public health and safety. The need to detect trace amounts of fentanyl in complex mixtures with other drugs or interferents, and the continued emergence of new fentanyl analogs, further complicates detection.

Impact of Guest Orientation in Host-Guest Supramolecular Hydrogels.

Host-guest interactions have been increasingly explored for use in the dynamic physical cross-linking of polymeric precursors to form hydrogel networks. However, the orientation of guest motifs is restricted upon macromolecule conjugation. The implications of such restriction on both the kinetics and thermodynamics of the resulting host-guest supramolecular cross-links are poorly understood.

Lignin deoxygenation for the production of sustainable aviation fuel blendstocks.

Lignin is an abundant source of renewable aromatics that has long been targeted for valorization. Traditionally, the inherent heterogeneity and reactivity of lignin has relegated it to direct combustion, but its higher energy density compared with polysaccharides makes it an ideal candidate for biofuel production. This Review critically assesses lignin's potential as a substrate for sustainable aviation fuel blendstocks.

Designing Phenolphthalein-Based Adsorptive Membranes for the High-Affinity, High-Capacity Capture of Contaminants from Water.

The selective removal of solutes is crucial for ensuring a sustainable water supply, recovering resources, and cost-effective biomanufacturing. Adsorptive membranes are promising in this regard due to their rapid mass transfer and low energy demands. However, state-of-the-art adsorptive membranes offer limited pore sizes and surface chemistries.

Engineering Supramolecular Nanofiber Depots from a Glucagon-Like Peptide-1 Therapeutic.

Diabetes and obesity have emerged as major global health concerns. Glucagon-like peptide-1 (GLP-1), a natural incretin hormone, stimulates insulin production and suppresses glucagon secretion to stabilize and reduce blood glucose levels and control appetite. The therapeutic use of GLP-1 receptor agonists (e.

Iterative Design Reveals Molecular Domain Relationships in Supramolecular Peptide-Drug Conjugates.

Supramolecular peptide-drug conjugates (sPDCs) are prepared by covalent attachment of a drug moiety to a peptide motif programmed for one-dimensional self-assembly, with subsequent physical entanglement of these fibrillar structures enabling formation of nanofibrous hydrogels. This class of prodrug materials presents an attractive platform for mass-efficient and site-specific delivery of therapeutic agents using a discrete, single-component molecular design. However, a continued challenge in sPDC development is elucidating relationships between supramolecular interactions in their drug and peptide domains and the resultant impacts of these domains on assembly outcomes and material properties.

Strain-Stiffening Mechanoresponse in Dynamic-Covalent Cellulose Hydrogels.

Mechanical stimuli such as strain, force, and pressure are pervasive within and beyond the human body. Mechanoresponsive hydrogels have been engineered to undergo changes in their physicochemical or mechanical properties in response to such stimuli. Relevant responses can include strain-stiffening, self-healing, strain-dependent stress relaxation, and shear rate-dependent viscosity.

Using a biocatalyzed reaction cycle for transient and pH-dependent host-guest supramolecular hydrogels.

The formation of transient structures plays important roles in biological processes, capturing temporary states of matter through influx of energy or biological reaction networks catalyzed by enzymes. These natural transient structures inspire efforts to mimic this elegant mechanism of structural control in synthetic analogues. Specifically, though traditional supramolecular materials are designed on the basis of equilibrium formation, recent efforts have explored out-of-equilibrium control of these materials using both direct and indirect mechanisms; the preponderance of such works has been in the area of low molecular weight gelators.

Engineering a Pathway to Glucose-Responsive Therapeutics.

In 2014, the American Diabetes Association instituted a novel funding paradigm to support diabetes research through its Pathway to Stop Diabetes program. This program took a multifaceted approach to providing key funding to diabetes researchers to advance a broad spectrum of research programs on all aspects of understanding, managing, and treating diabetes. Here, the personal perspective of a 2019 Pathway Accelerator awardee is offered, describing a research program seeking to advance a materials-centered approach to engineering glucose-responsive devices and new delivery tools for better therapeutic outcomes in treating diabetes.

Engineering a Pathway to Glucose-Responsive Therapeutics.

In 2014, the American Diabetes Association instituted a novel funding paradigm to support diabetes research through its Pathway to Stop Diabetes® Program. Pathway took a multifaceted approach to provide key funding to diabetes researchers in advancing a broad spectrum of research programs centered on all aspects of understanding, managing, and treating diabetes. Herein the personal perspective of a 2019 Pathway Accelerator awardee is offered, describing a research program seeking to advance a materials-centered approach to engineering glucose-responsive devices and new delivery tools for better therapeutic outcomes in treating diabetes.

APOE ε4 carriage associates with improved myocardial performance from adolescence to older age.

Background: Although APOE ε4 allele carriage confers a risk for coronary artery disease, its persistence in humans might be explained by certain survival advantages (antagonistic pleiotropy).

Methods: Combining data from ~ 37,000 persons from three older age British cohorts (1946 National Survey of Health and Development [NSHD], Southall and Brent Revised [SABRE], and UK Biobank) and one younger age cohort (Avon Longitudinal Study of Parents and Children [ALSPAC]), we explored whether APOE ε4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional metrics by echocardiography and cardiovascular magnetic resonance (CMR).

Results: Compared to the non-APOE ε4 group, APOE ε4 carriers had similar cardiac phenotypes in terms of LV ejection fraction, E/e', posterior wall and interventricular septal thickness, and LV mass.

Glucose-Driven Droplet Formation in Complexes of a Supramolecular Peptide and Therapeutic Protein.

Biology achieves remarkable function through processes arising from spontaneous or transient liquid-liquid phase separation (LLPS) of proteins and other biomolecules. While polymeric systems can achieve similar phenomena through simple or complex coacervation, LLPS with supramolecular materials has been less commonly shown. Functional applications for synthetic LLPS systems are an expanding area of emphasis, with particular focus on capturing the transient and dynamic state of these structures for use in biomedicine.

Heart Rhythm New Zealand consensus statement on the practical management of cardiac implanted electronic devices in the peri-operative environment.

Electrosurgery is commonly used during a range of operations in order to maintain effective haemostasis. This can cause electromagnetic interference (EMI) with cardiac implanted electronic devices (CIEDs), which prevents normal device function. CIEDs include pacemakers (PPM), implantable cardiac defibrillators (ICD), cardiac resynchronisation therapy devices-both pacemakers and defibrillators (CRT-P/CRT-D)-and implantable loop recorders (ILRs).

Electrophysiological Characterization of Subclinical and Overt Hypertrophic Cardiomyopathy by Magnetic Resonance Imaging-Guided Electrocardiography.

Background: Ventricular arrhythmia in hypertrophic cardiomyopathy (HCM) relates to adverse structural change and genetic status. Cardiovascular magnetic resonance (CMR)-guided electrocardiographic imaging (ECGI) noninvasively maps cardiac structural and electrophysiological (EP) properties.

Objectives: The purpose of this study was to establish whether in subclinical HCM (genotype [G]+ left ventricular hypertrophy [LVH]-), ECGI detects early EP abnormality, and in overt HCM, whether the EP substrate relates to genetic status (G+/G-LVH+) and structural phenotype.

Glucose-Triggered Gelation of Supramolecular Peptide Nanocoils with Glucose-Binding Motifs.

Peptide self-assembly is a powerful tool to prepare functional materials at the nanoscale. Often, the resulting materials have high aspect-ratio, with intermolecular β-sheet formation underlying 1D fibrillar structures. Inspired by dynamic structures in nature, peptide self-assembly is increasingly moving toward stimuli-responsive designs wherein assembled structures are formed, altered, or dissipated in response to a specific cue.