Publications

The low endogenous regenerative capacity of the heart,added tothe prevalence of cardiovascular diseases, triggered the advent ofcardiac tissue engineering in the last decades. The myocardial nicheplays a critical role in directing the function and fate of cardiomyocytes;therefore, engineering a biomimetic scaffold holds excellent promise.We produced an electroconductive cardiac patch of bacterial nanocellulose(BC) with polypyrrole nanoparticles (Ppy NPs) to mimic the naturalmyocardial microenvironment. BC offers a 3D interconnected fiber structurewith high flexibility, which is ideal for hosting Ppy nanoparticles.BC-Ppy composites were produced by decorating the network of BC fibers(65 & PLUSMN; 12 nm) with conductive Ppy nanoparticles (83 & PLUSMN; 8 nm).Ppy NPs effectively augment the conductivity, surface roughness, andthickness of BC composites despite reducing scaffolds' transparency.BC-Ppy composites were flexible (up to 10 mM Ppy), maintained theirintricate 3D extracellular matrix-like mesh structure in all Ppy concentrationstested, and displayed electrical conductivities in the range of nativecardiac tissue. Furthermore, these materials exhibit tensile strength,surface roughness, and wettability values appropriate for their finaluse as cardiac patches. In vitro experiments withcardiac fibroblasts and H9c2 cells confirmed the exceptional biocompatibilityof BC-Ppy composites. BC-Ppy scaffolds improved cell viability andattachment, promoting a desirable cardiomyoblast morphology. Biochemicalanalyses revealed that H9c2 cells showed different cardiomyocyte phenotypesand distinct levels of maturity depending on the amount of Ppy inthe substrate used. Specifically, the employment of BC-Ppy compositesdrives partial H9c2 differentiation toward a cardiomyocyte-like phenotype.The scaffolds increase the expression of functional cardiac markersin H9c2 cells, indicative of a higher differentiation efficiency,which is not observed with plain BC. Our results highlight the remarkablepotential use of BC-Ppy scaffolds as a cardiac patch in tissue regenerativetherapies.

JTD Keywords: bacterial nanocellulose, cardiac patches, conducting polymers, polypyrrole, Arrhythmias, Bacterial nanocellulose, Biomaterials, Cardiac patches, Cell therapy, Cellulose, Conductingpolymers, H9c2, In-vitro, Polymer, Polypyrrole, Scaffolds, Tissue, Tissue engineering, Viability

Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case-control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini-Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias.

JTD Keywords: Arrhythmias, Fish-oil, Omega-3-fatty-acids, Sudden cardiac death

Background: The peptide hormone relaxin-2 (RLX) exerts beneficial effects during myocardial ischemia, but functional data on lower-dose RLX in myocardial infarction (MI) is lacking. Therefore, we investigated the impact of 75 μg/kg/d RLX treatment on electrical vulnerability and left ventricular function in a mouse model of MI. Methods and results: Standardized cryoinfarction of the left anterior ventricular wall was performed in mice. A two week treatment period with vehicle or RLX via subcutaneously implanted osmotic minipumps was started immediately after MI. The relaxin receptor RXFP1 was expressed on ventricular/atrial cardiomyocytes, myofibroblasts, macrophages and endothelial but not vascular smooth muscle cells of small coronary vessels. RLX treatment resulted in a significant reduction of ventricular tachycardia inducibility (vehicle: 91%, RLX: 18%, p < 0.0001) and increased epicardial conduction velocity in the left ventricle and borderzone. Furthermore, left ventricular function following MI was improved in RLX treated mice (left ventricular ejection fraction; vehicle: 41.1 ± 1.9%, RLX: 50.5 ± 3.5%, p = 0.04). Interestingly, scar formation was attenuated by RLX with decreased transcript expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1β were upregulated in hearts of vehicle treated animals compared to mice without MI. Application of RLX attenuated this inflammatory response. In addition, macrophage infiltration was reduced in the borderzone of RLX treated mice. Conclusion: Treatment with lower-dose RLX in mice prevents post-infarction ventricular tachycardia due to attenuation of scar formation and cardiac inflammation. Therefore, RLX could be evaluated as new therapeutic option in the treatment of MI.

JTD Keywords: Arrhythmia, Myocardial infarction, Relaxin-2, Ventricular tachycardia