A Combined Computational and Experimental Analysis of PLA and PCL Hybrid Nanocomposites 3D Printed Scaffolds for Bone Regeneration.

A combined computational and experimental study of 3D-printed scaffolds made from hybrid nanocomposite materials for potential applications in bone tissue engineering is presented. Polycaprolactone (PCL) and polylactic acid (PLA), enhanced with chitosan (CS) and multiwalled carbon nanotubes (MWCNTs), were investigated in respect of their mechanical characteristics and responses in fluidic environments. A novel scaffold geometry was designed, considering the requirements of cellular proliferation and mechanical properties. Specimens with the same dimensions and porosity of 45% were studied to fully describe and understand the yielding behavior. Mechanical testing indicated higher apparent moduli in the PLA-based scaffolds, while compressive strength decreased with CS/MWCNTs reinforcement due to nanoscale challenges in 3D printing. Mechanical modeling revealed lower stresses in the PLA scaffolds, attributed to the molecular mass of the filler. Despite modeling challenges, adjustments improved simulation accuracy, aligning well with experimental values. Material and reinforcement choices significantly influenced responses to mechanical loads, emphasizing optimal structural robustness. Computational fluid dynamics emphasized the significance of scaffold permeability and wall shear stress in influencing bone tissue growth. For an inlet velocity of 0.1 mm/s, the permeability value was estimated at 4.41 × 10-9 m2, which is in the acceptable range close to human natural bone permeability. The average wall shear stress (WSS) value that indicates the mechanical stimuli produced by cells was calculated to be 2.48 mPa, which is within the range of the reported literature values for promoting a higher proliferation rate and improving osteogenic differentiation. Overall, a holistic approach was utilized to achieve a delicate balance between structural robustness and optimal fluidic conditions, in order to enhance the overall performance of scaffolds in tissue engineering applications.

Computational Fluid Dynamic Analysis of customised 3D-printed bone scaffolds with different architectures.

Through the recent years, tissue engineering has been proven as a solid substitute of autografts in the stimulation of bone tissue regeneration, through the development of three dimensional (3D) porous matrices, commonly known as scaffolds. In this work, we analysed two scaffold structures with 500µm pore size, by performing computational fluid dynamics simulations, to compare permeability, Wall Shear Stress (WSS), velocity and pressure distributions. Taking into account those parameters the geometry named as "PCL-50" was the best to anticipate showing a superior performance in supporting cell growth due to the improved flow characteristics in the scaffold.Clinical Relevance- Bone defects that require invasive surgical treatment with high risks in terms of success and effectiveness. Bone tissue engineering (BTE) in combination with the use of computational fluid dynamics (CFD) analysis tools aim to assist in designing optimal scaffolds that better promote bone growth and repair. The fluid dynamic characteristics of a porous scaffold plays a vital role in cell viability and cell growth, affecting the osteogenic performance of the scaffold.

Comparison of three U-Net family architectures for left ventricular myocardial wall automatic segmentation.

Left ventricular (LV) segmentation is an important process which can provide quantitative clinical measurements such as volume, wall thickness and ejection fraction. The development of an automatic LV segmentation procedure is a challenging and complicated task mainly due to the variation of the heart shape from patient to patient, especially for those with pathological and physiological changes. In this study, we focus on the implementation, evaluation and comparison of three different Deep Learning architectures of the U-Net family: the custom 2-D U-Net, the ResU-Net++ and the DenseU-Net, in order to segment the LV myocardial wall. Our approach was applied to cardiac CT datasets specifically derived from patients with hypertrophic cardiomyopathy. The results of the models demonstrated high performance in the segmentation process with minor losses. The model revealed a dice score for U-Net, Res-U-net++ and Dense U-Net, 0.81, 0.82 and 0.84, respectively.

Medium-term Electrophysiologic Effects of a Cellularized Scaffold Implanted in Rats After Myocardial Infarction.

Background Cardiac repair strategies are being evaluated for myocardial infarctions, but the safety issues regarding their arrhythmogenic potential remain unresolved. By utilizing the in-vivo rat model, we have examined the medium-term electrophysiologic effects of a biomaterial scaffold that has been cellularized with spheroids of human adipose tissue, derived from mesenchymal stem cells and umbilical vein endothelial cells. Methods Mesenchymal stem cells, which exhibit adequate differentiation capacity, were co-cultured with umbilical vein endothelial cells and were seeded on an alginate based scaffold. After in-vitro characterization, the cellularized scaffold was implanted in (n=15) adult Wistar rats 15 min post ligation of the left coronary artery, with an equal number of animals serving as controls. Two weeks thereafter, monophasic action potentials were recorded and activation-mapping was performed with a multi-electrode array. An arrhythmia score for inducible ventricular tachyarrhythmias was calculated after programmed electrical stimulation. Results The arrhythmia score was comparable between the treated animals and controls. No differences were detected in the local conduction at the infarct border and in the voltage rise in monophasic action potential recordings. Treatment did not affect the duration of local repolarization, but tended to enhance its dispersion. Conclusions The fabricated bi-culture cellularized scaffold displayed favorable properties after in-vitro characterization. Medium-term electrophysiologic assessment after implantation in the infarcted rat myocardium revealed low arrhythmogenic potential, but the long-term effects on repolarization dispersion will require further investigation.

Prolonged intra-myocardial growth hormone administration ameliorates post-infarction electrophysiologic remodeling in rats.

Experimental studies indicate improved ventricular function after treatment with growth hormone (GH) post-myocardial infarction, but its effect on arrhythmogenesis is unknown. Here, we assessed the medium-term electrophysiologic remodeling after intra-myocardial GH administration in (n = 33) rats. GH was released from an alginate scaffold, injected around the ischemic myocardium after coronary ligation. Two weeks thereafter, ventricular tachyarrhythmias were induced by programmed electrical stimulation. Monophasic action potentials were recorded from the infarct border, coupled with evaluation of electrical conduction and repolarization from a multi-electrode array. The arrhythmia score was lower in GH-treated rats than in alginate-treated rats or controls. The shape and the duration of the action potential at the infarct border were preserved, and repolarization-dispersion was attenuated after GH; moreover, voltage rise was higher and activation delay was shorter. GH normalized also right ventricular parameters. Intra-myocardial GH preserved electrical conduction and repolarization-dispersion at the infarct border and decreased the incidence of induced tachyarrhythmias in rats post-ligation. The long-term antiarrhythmic potential of GH merits further study.

Intra-myocardial growth hormone administration ameliorates arrhythmogenesis during ischemia-reperfusion in rats.

Growth hormone, currently under evaluation for the prevention of left ventricular remodeling post-myocardial infarction, displays antiarrhythmic properties in the acute setting. However, it is uncertain whether these actions are retained after ischemia/reperfusion. Using implanted telemetry transmitters, we examined the effects of prolonged, intra-myocardial growth hormone administration in conscious rats. During a 24-h observation period, ventricular tachyarrhythmias and sympathetic activation were attenuated in treated rats, whereas infarct-size was unchanged. These findings call for further study on the antiarrhythmic effects of growth hormone and on the underlying mechanisms.

Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity.

Embryonic Stem (ES) or induced Pluripotent Stem (iPS) cells are important sources for cardiomyocyte generation, targeted for regenerative therapies. Several in vitro protocols are currently utilized for their differentiation, but the value of cell-based approaches remains unclear. Here, we characterized a cardiovascular progenitor population derived during ES differentiation, after selection based on VE-cadherin promoter (Pvec) activity. ESCs were genetically modified with an episomal vector, allowing the expression of puromycin resistance gene, under Pvec activity. Puromycin-surviving cells displayed cardiac and endothelial progenitor cells characteristics. Expansion and self-renewal of this cardiac and endothelial dual-progenitor population (CEDP) were achieved by Wnt/ß-catenin pathway activation. CEDPs express early cardiac developmental stage-specific markers but not markers of differentiated cardiomyocytes. Similarly, CEDPs express endothelial markers. However, CEDPs can undergo differentiation predominantly to cTnT+ (~47%) and VE-cadherin+ (~28%) cells. Transplantation of CEDPs in the left heart ventricle of adult rats showed that CEDPs-derived cells survive and differentiate in vivo for at least 14 days after transplantation. A novel, dual-progenitor population was isolated during ESCs differentiation, based on Pvec activity. This lineage can self-renew, permitting its maintenance as a source of cardiovascular progenitor cells and constitutes a useful source for regenerative approaches.