Pristine Photopolymerizable Gelatin Hydrogels: A Low-Cost and Easily Modifiable Platform for Biomedical Applications.

The study addresses the challenge of temperature sensitivity in pristine gelatin hydrogels, widely used in biomedical applications due to their biocompatibility, low cost, and cell adhesion properties. Traditional gelatin hydrogels dissolve at physiological temperatures, limiting their utility. Here, we introduce a novel method for creating stable hydrogels at 37 °C using pristine gelatin through photopolymerization without requiring chemical modifications.

Experimentally-guided in silico design of engineered heart tissues to improve cardiac electrical function after myocardial infarction.

Engineered heart tissues (EHTs) built from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) showed promising results for cardiac function restoration following myocardial infarction. Nevertheless, human iPSC-CMs have longer action potential and lower cell-to-cell coupling than adult-like CMs. These immature electrophysiological properties favor arrhythmias due to the generation of electrophysiological gradients when hiPSC-CMs are injected in the cardiac tissue.

Biomaterials-Based Antioxidant Strategies for the Treatment of Oxidative Stress Diseases.

Oxidative stress is characterized by an increase in reactive oxygen species or a decrease in antioxidants in the body. This imbalance leads to detrimental effects, including inflammation and multiple chronic diseases, ranging from impaired wound healing to highly impacting pathologies in the neural and cardiovascular systems, or the bone, amongst others. However, supplying compounds with antioxidant activity is hampered by their low bioavailability.

Generation of heart and vascular system in rodents by blastocyst complementation.

Generating organs from stem cells through blastocyst complementation is a promising approach to meet the clinical need for transplants. In order to generate rejection-free organs, complementation of both parenchymal and vascular cells must be achieved, as endothelial cells play a key role in graft rejection. Here, we used a lineage-specific cell ablation system to produce mouse embryos unable to form both the cardiac and vascular systems.

Fabrication of human myocardium using multidimensional modelling of engineered tissues.

Biofabrication of human tissues has seen a meteoric growth triggered by recent technical advancements such as human induced pluripotent stem cells (hiPSCs) and additive manufacturing. However, generation of cardiac tissue is still hampered by lack of adequate mechanical properties and crucially by the often unpredictable post-fabrication evolution of biological components. In this study we employ melt electrowriting (MEW) and hiPSC-derived cardiac cells to generate fibre-reinforced human cardiac minitissues.

A Fibrosis Biomarker Early Predicts Cardiotoxicity Due to Anthracycline-Based Breast Cancer Chemotherapy.

Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC.

Multiplexing physical stimulation on single human induced pluripotent stem cell-derived cardiomyocytes for phenotype modulation.

Traditional in vitro bioengineering approaches whereby only individual biophysical cues are manipulated at any one time are highly inefficient, falling short when recapitulating the complexity of the cardiac environment. Multiple biophysical cues are present in the native myocardial niche and are essential during development, as well as in maintenance of adult cardiomyocyte (CM) phenotype in both health and disease. This study establishes a novel biofabrication workflow to study and manipulate hiPSC-CMs and to understand how these cells respond to a multiplexed biophysical environment, namely 3D shape and substrate stiffness, at a single cell level.

Engineering and Assessing Cardiac Tissue Complexity.

Cardiac tissue engineering is very much in a current focus of regenerative medicine research as it represents a promising strategy for cardiac disease modelling, cardiotoxicity testing and cardiovascular repair. Advances in this field over the last two decades have enabled the generation of human engineered cardiac tissue constructs with progressively increased functional capabilities. However, reproducing tissue-like properties is still a pending issue, as constructs generated to date remain immature relative to native adult heart.

Cells, Materials, and Fabrication Processes for Cardiac Tissue Engineering.

Cardiovascular disease is the number one killer worldwide, with myocardial infarction (MI) responsible for approximately 1 in 6 deaths. The lack of endogenous regenerative capacity, added to the deleterious remodelling programme set into motion by myocardial necrosis, turns MI into a progressively debilitating disease, which current pharmacological therapy cannot halt. The advent of Regenerative Therapies over 2 decades ago kick-started a whole new scientific field whose aim was to prevent or even reverse the pathological processes of MI.

Engineering a Humanised Niche to Support Human Haematopoiesis in Mice: Novel Opportunities in Modelling Cancer.

Despite the bone marrow microenvironment being widely recognised as a key player in cancer research, the current animal models that represent a human haematopoietic system lack the contribution of the humanised marrow microenvironment. Here we describe a murine model that relies on the combination of an orthotopic humanised tissue-engineered bone construct (ohTEBC) with patient-specific bone marrow (BM) cells to create a humanised bone marrow (hBM) niche capable of supporting the engraftment of human haematopoietic cells. Results showed that this model supports the engraftment of human CD34 cells from a healthy BM with human haematopoietic cells migrating into the mouse BM, human BM compartment, spleen and peripheral blood.

Exploring the inner environment of protein hydrogels with fluorescence spectroscopy towards understanding their drug delivery capabilities.

Hydrogels are common platforms for drug delivery applications. Amongst the different loading and release methodologies, physisorption loading and passive release stand out for their straightforwardness. However, evaluating the inner environment and the surface of the polymer can be complicated, as they can be very different from the properties of the monomer composing the hydrogel.

Activatable cell-biomaterial interfacing with photo-caged peptides.

Spatio-temporally tailoring cell-material interactions is essential for developing smart delivery systems and intelligent biointerfaces. Here we report new photo-activatable cell-material interfacing systems that trigger cellular uptake of various cargoes and cell adhesion towards surfaces. To achieve this, we designed a novel photo-caged peptide which undergoes a structural transition from an antifouling ligand to a cell-penetrating peptide upon photo-irradiation.

Surface Dynamics and Ligand-Core Interactions of Quantum Sized Photoluminescent Gold Nanoclusters.

Quantum-sized metallic clusters protected by biological ligands represent a new class of luminescent materials; yet the understanding of structural information and photoluminescence origin of these ultrasmall clusters remains a challenge. Herein we systematically study the surface ligand dynamics and ligand-metal core interactions of peptide-protected gold nanoclusters (AuNCs) with combined experimental characterizations and theoretical molecular simulations. We show that the peptide sequence plays an important role in determining the surface peptide structuring, interfacial water dynamics and ligand-Au core interaction, which can be tailored by controlling peptide acetylation, constituent amino acid electron donating/withdrawing capacity, aromaticity/hydrophobicity and by adjusting environmental pH.

Elastic serum-albumin based hydrogels: mechanism of formation and application in cardiac tissue engineering.

Hydrogels are promising materials for mimicking the extra-cellular environment. Here, we present a simple methodology for the formation of a free-standing viscoelastic hydrogel from the abundant and low cost protein serum albumin. We show that the mechanical properties of the hydrogel exhibit a complicated behaviour as a function of the weight fraction of the protein component.

Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information.

Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis.

Quantitative volumetric Raman imaging of three dimensional cell cultures.

The ability to simultaneously image multiple biomolecules in biologically relevant three-dimensional (3D) cell culture environments would contribute greatly to the understanding of complex cellular mechanisms and cell-material interactions. Here, we present a computational framework for label-free quantitative volumetric Raman imaging (qVRI). We apply qVRI to a selection of biological systems: human pluripotent stem cells with their cardiac derivatives, monocytes and monocyte-derived macrophages in conventional cell culture systems and mesenchymal stem cells inside biomimetic hydrogels that supplied a 3D cell culture environment.