Traumatic brain injury (TBI) leads to cellular loss, destabilization of membranes, disruption of synapses and altered brain connectivity, and increased risk of neurodegenerative disease. A significant and long-lasting decrease in phospholipids (PLs), essential membrane constituents, has recently been reported in plasma and brain tissue, in human and experimental TBI. We hypothesized that supporting PL synthesis post-injury could improve outcome post-TBI. We tested this hypothesis using a multi-nutrient combination designed to support the biosynthesis of PLs and available for clinical use. The multi-nutrient, Fortasyn ^® Connect (FC), contains polyunsaturated omega-3 fatty acids, choline, uridine, vitamins, cofactors required for PL biosynthesis, and has been shown to have significant beneficial effects in early Alzheimer's disease. Male C57BL/6 mice received a controlled cortical impact injury and then were fed a control diet or a diet enriched with FC for 70 days. FC led to a significantly improved sensorimotor outcome and cognition, reduced lesion size and oligodendrocyte loss, and it restored myelin. It reversed the loss of the synaptic protein synaptophysin and decreased levels of the axon growth inhibitor, Nogo-A, thus creating a permissive environment. It decreased microglia activation and the rise in ß-amyloid precursor protein and restored the depressed neurogenesis. The effects of this medical multi-nutrient suggest that support of PL biosynthesis post-TBI, a new treatment paradigm, has significant therapeutic potential in this neurological condition for which there is no satisfactory treatment. The multi-nutrient tested has been used in dementia patients and is safe and well tolerated, which would enable rapid clinical exploration in TBI.

Catheter-related infections are a common worldwide health problem, highlighting the need for antimicrobial catheters. Here, antibacterial potential of graphene nanoplatelets (GNP) incorporated in the commonly used polymer for catheter manufacture—polyurethane (PU)—is investigated. Two strategies are explored: melt-blending, producing a composite, and dip coating, where a composite layer is deposited on top of PU. GNP with different lateral sizes and oxidation degrees—GNP-M5, GNP-M15, GNP-M5ox, GNP-M15ox—are applied in both strategies, and the antimicrobial potential towards Staphylococcus epidermidis of GNP dispersions and GNP-containing PU evaluated. As dispersions, oxidized and smaller GNP powders (GNP-M5ox) inhibit 74% bacteria growth at 128 µg/mL. As surfaces, GNP exposure strongly impacts their antimicrobial profile: GNP absence at the surface of composites yields no significant effects on bacteria, while by varying GNP: PU ratio and GNP concentration, coatings enhance GNP exposure, depicting an antimicrobial profile. Oxidized GNP-containing coatings induce higher antibacterial effect than non-oxidized forms, particularly with smaller GNPox, where a homogeneous layer of fused platelets is formed on PU, leading to 70% reduction in bacterial adhesion and 70% bacterial death. This pioneering work unravels how to turn a polymer clinically used to produce catheters into an antimicrobial surface, crucial to reducing risk of infection associated with catheterization.

Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during coronary artery bypass grafting (CABG) from two MI cohorts, patients with non-ST-segment elevation MI (NSTEMI) and patients with ST-segment elevation MI (STEMI), and a control group composed of patients with stable angina and without previous history of MI. The PF miR content was analyzed by small RNA sequencing, and its biological effect was assessed on human cardiac fibroblasts. PF accumulates fibrotic and inflammatory molecules in STEMI patients, namely causing the soluble suppression of tumorigenicity 2 (ST-2), which inversely correlates with the left ventricle ejection fraction. Although the PF of the three patient groups induce similar levels of fibroblast-to-myofibroblast activation in vitro, RNA sequencing revealed that PF from STEMI patients is particularly enriched not only in pro-fibrotic miRs but also anti-fibrotic miRs. Among those, miR-22-3p was herein found to inhibit TGF-β-induced human cardiac fibroblast activation in vitro. PF constitutes an attractive source for screening diagnostic/prognostic miRs and for unveiling novel therapeutic targets in cardiac fibrosis.

Cardiovascular diseases (CVD), the leading cause of death worldwide, and their strong association with fibrosis highlight the pressing need for innovative antifibrotic therapies. In vitro models have emerged as valuable tools for replicating cardiac fibrosis ‘in a dish’, facilitating the study of disease mechanisms and serving as platforms for drug testing and development. These in vitro systems encompass 2D and 3D models, each with its own limitations and advantages. 2D models offer high reproducibility, cost-effectiveness, and high-throughput capabilities, but they oversimplify the complex fibrotic environment. On the other hand, 3D models provide greater biological relevance but are more complex, harder to reproduce, and less suited for high-throughput screening. The choice of model depends on the specific research question and the stage of drug development. Despite significant progress, challenges remain, including the integration of immune cells in cardiac fibrosis and optimizing the scalability and throughput of highly biomimetic systems. Herein, we review recent in vitro cardiac fibrosis models, with a focus on their shared characteristics and remaining challenges, and explore how in vitro fibrosis models of other organs could inspire novel approaches in cardiac research, showcasing potential strategies that could be adapted to refine myocardial fibrosis models.

The authors wish to make the following corrections to this paper