Potential of Angiotensin-(1-7) in COVID-19 Treatment.

The new coronavirus currently named SARS-CoV-2 was announced by the World Health Organization as the virus causing the COVID-19 pandemic. The pathogenesis of SARS-CoV-2 initiates upon contact of a structural spike protein with the angiotensin II-converting enzyme receptor, leading to the induction of inflammatory mechanisms and progression to severe disease in some cases. Currently, studies have emerged linking COVID-19 with angiotensin-(1-7), demonstrating the potential of angiotensin-(1-7)/Mas Receptor axis induction to control disease severity due to its antiinflammatory, vasodilator, antioxidant, antiproliferative, anticoagulant, antiangiogenic and fibrosis inhibitory effects. The renin angiotensin-system peptide Angiotensin-(1-7) shows a high therapeutic potential for COVID-19 mainly because of its ability to counteract the adverse effects caused in various organs due to angiotensin II-converting enzyme blockade. In light of these factors, the use of convalescent plasma conjugated therapy and Ang (1-7) agonists for the treatment of COVID-19 patients could be recommended. The differential expression of ACE2 and the varied response to SARSCoV- 2 are thought to be connected. According to several investigations, ACE2 antibodies and pharmacological inhibitors might be used to prevent viral entry. Given its capacity to eliminate the virus while ensuring lung and cardiovascular protection by regulating the inflammatory response, angiotensin-( 1-7) is expected to be a safe choice. However, more clinical evidence is required to clarify the therapeutic usage of this peptide. The aim of this review article is to present an update of scientific data and clinical trials on the therapeutic potential of angiotensin-(1-7) in patients with COVID-19.

Electrochemical and Electroconductive Behavior of Silk Fibroin Electrospun Membrane Coated with Gold or Silver Nanoparticles.

The surface modification of materials obtained from natural polymers, such as silk fibroin with metal nanoparticles that exhibit intrinsic electrical characteristics, allows the obtaining of biocomposite materials capable of favoring the propagation and conduction of electrical impulses, acting as communicating structures in electrically isolated areas. On that basis, this investigation determined the electrochemical and electroconductive behavior through electrochemical impedance spectroscopy of a silk fibroin electrospun membrane from silk fibrous waste functionalized with gold or silver nanoparticles synthetized by green chemical reduction methodologies. Based on the results obtained, we found that silk fibroin from silk fibrous waste (SFw) favored the formation of gold (AuNPs-SFw) and silver (AgNPs-SFw) nanoparticles, acting as a reducing agent and surfactant, forming a micellar structure around the individual nanoparticle. Moreover, different electrospinning conditions influenced the morphological properties of the fibers, in the presence or absence of beads and the amount of sample collected. Furthermore, treated SFw electrospun membranes, functionalized with AuNPs-SFw or AgNPS-SFw, allowed the conduction of electrical stimuli, acting as stimulators and modulators of electric current.

Cell culture: a promising environment for research on cardiology / Cultivos celulares: un entorno promisorio para la investigación en cardiología

Abstract At present, tissue engineering is transforming the area of cardiovascular regenerative medicine, which combines the principles and methods of materials engineering and biological sciences, interacting with biochemical and physicochemical factors, for the understanding of their structure-function relationship. Thus, the course of diseases is reoriented by implementing methods and procedures involved in the regeneration of organs and tissues by means of the interaction with biocompatible matrices, pre-treated organs or stem cell management, among others, thus recovering the functionality in the system affected by acquired pathologies, alterations or congenital defects. Consequently, these procedures are increasingly becoming one the most promising treatment alternative for patients who suffer from any type of functional deficit. Known that all these possibilities make cell cultures a promising study environment to be used in biomedical applications, especially in tissue engineering and regenerative medicine, this manuscript presents a general reviews of established cell lines or primary tissue lines and how cell cultures serve as a model before experimental work on laboratory animals and human subjects which makes it a valuable tool for broad models of study in the research on cardiology.

Resumen En la actualidad, la ingeniería de tejidos está transformando el área de la medicina regenerativa cardiovascular, combinando los principios y métodos de la ingeniería de materiales y las ciencias biológicas, interactuando entre factores bioquímicos y fisicoquímicos, para la comprensión de su relación estructura-función. Así, el curso de las enfermedades se viene a reorientar mediante la implementación de métodos y procedimientos implicados en la regeneración de órganos y tejidos a través de la interacción con matrices biocompatibles, órganos pretratados o manejo de células madre, entre otros, recuperando así la funcionalidad en el sistema afectado por enfermedades adquiridas y alteraciones o defectos congénitos. En consecuencia, estos procedimientos se están convirtiendo en una de las alternativas de tratamiento cada vez más prometedoras para los pacientes que sufren de algún tipo de alteración funcional. Considerando que todas estas posibilidades hacen de los cultivos celulares un entorno de estudio prometedor para ser utilizado en aplicaciones biomédicas, especialmente en ingeniería de tejidos y medicina regenerativa, este manuscrito presenta una revisión general de las líneas celulares establecidas o líneas de tejido primario y cómo los cultivos celulares sirven como modelo de evaluación antes del trabajo experimental en animales de laboratorio y sujetos humanos, lo cual los convierte en una herramienta valiosa para amplios modelos de estudio en la investigación en cardiología.

Effect of Molecular Weight and Nanoarchitecture of Chitosan and Polycaprolactone Electrospun Membranes on Physicochemical and Hemocompatible Properties for Possible Wound Dressing.

Tissue engineering has focused on the development of biomaterials that emulate the native extracellular matrix. Therefore, the purpose of this research was oriented to the development of nanofibrillar bilayer membranes composed of polycaprolactone with low and medium molecular weight chitosan, evaluating their physicochemical and biological properties. Two-bilayer membranes were developed by an electrospinning technique considering the effect of chitosan molecular weight and parameter changes in the technique. Subsequently, the membranes were evaluated by scanning electron microscopy, Fourier transform spectroscopy, stress tests, permeability, contact angle, hemolysis evaluation, and an MTT test. From the results, it was found that changes in the electrospinning parameters and the molecular weight of chitosan influence the formation, fiber orientation, and nanoarchitecture of the membranes. Likewise, it was evidenced that a higher molecular weight of chitosan in the bilayer membranes increases the stiffness and favors polar anchor points. This increased Young's modulus, wettability, and permeability, which, in turn, influenced the reduction in the percentage of cell viability and hemolysis. It is concluded that the development of biomimetic bilayer nanofibrillar membranes modulate the physicochemical properties and improve the hemolytic behavior so they can be used as a hemocompatible biomaterial.

Effect of sequential electrospinning and co-electrospinning on morphological and fluid mechanical wall properties of polycaprolactone and bovine gelatin scaffolds, for potential use in small diameter vascular grafts.

BACKGROUND: Nowadays, the engineering vascular grafts with a diameter less than 6 mm by means of electrospinning, is an attracted alternative technique to create different three-dimensional microenvironments with appropriate physicochemical properties to promote the nutrient transport and to enable the bioactivity, dynamic growth and differentiation of cells. Although the performance of a well-designed porous wall is key for these functional requirements maintaining the mechanical function, yet predicting the flow rate and cellular transport are still not widely understood and many questions remain open about new configurations of wall can be used for modifying the conventional electrospun samples. The aim of the present study was to evaluate the effect of fabrication techniques on scaffolds composed of bovine gelatin and polycaprolactone (PCL) developed by sequential electrospinning and co-electrospinning, on the morphology and fluid-mechanical properties of the porous wall. METHODOLOGY: For this purpose, small diameter tubular structures were manufactured and experimental tests were performed to characterize the crystallinity, morphology, wettability, permeability, degradability, and mechanical properties. Some samples were cross-linked with Glutaraldehyde (GA) to improve the stability of the gelatin fiber. In addition, it was analyzed how the characteristics of the scaffold favored the levels of cell adhesion and proliferation in an in vitro model of 3T3 fibroblasts in incubation periods of 24, 48 and 72 h. RESULTS: It was found that in terms of the morphology of tubular scaffolds, the co-electrospun samples had a better alignment with higher values of fiber diameters and apparent pore area than the sequential samples. The static permeability was more significant in the sequential scaffolds and the hydrophilic was higher in the co-electrospun samples. Therefore, the gelatin mass losses were less in the co-electrospun samples, which promote cellular functions. In terms of mechanical properties, no significant differences were observed for different types of samples. CONCLUSION: This research concluded that the tubular scaffolds generated by sequential and co-electrospinning with modification in the microarchitecture could be used as a vascular graft, as they have better permeability and wettability, interconnected pores, and a circumferential tensile strength similar to native vessel compared to the commercial graft analyzed.

Hemolytic, Biocompatible, and Functional Effect of Cellularized Polycaprolactone-Hydrolyzed Collagen Electrospun Membranes for Possible Application as Vascular Implants.

In search of bioactive vascular prostheses that exhibit greater biocompatibility through the combination of natural and synthetic polymers, tissue engineering from a biomimetic perspective has proposed the development of three-dimensional structures as therapeutic strategies in the field of cardiovascular medicine. Techniques such as electrospinning allow obtaining of scaffolds that emulate the microarchitecture of the extracellular matrix of native vessels; thus, this study aimed to evaluate the biological influence of microarchitecture on polycaprolactone (PCL) and hydrolyzed collagen (H-Col) electrospun scaffolds, which have a homogeneous (microscale) or heterogeneous (micro-nanoscale) fibrillar structure. The hemolytic, biocompatible, and functional effect of the scaffolds in interaction with an in vitro fibroblast model was determined, in view of its potential use for vascular implants. Scaffolds were characterized by scanning electron microscopy and atomic force microscopy, Fourier transform infrared spectroscopy, wettability, static permeability, tensile test, and degradation. In addition, direct and indirect 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were used to identify the cell viability of fibroblasts, fluorescence assays were performed to establish morphological changes of the cell nuclei, and the hemolytic effect of the scaffolds was calculated. Results showed that ethanol-treated biocompositescaffolds exhibited mass losses lower than 6.65% and slow wettability and absorption, resulting from an increase in secondary structures that contribute to the crystalline phase of H-Col. The scaffolds demonstrated stable degradation in saline during the incubation period because of the availability of soluble structures in aqueous media, and the inclusion of H-Col increased the elastic properties of the scaffold. As regards hemocompatibility, the scaffolds had hemolysis levels lower than 1%; moreover, in terms of biocompatible characteristics, scaffolds exhibited good adhesion, proliferation, and cell viability and insignificant changes in the circularity of the cell nuclei. However, scaffolds with homogeneous fibers showed cell agglomerates after 48 h of interaction. By contrast, permeability decreased as the incubation period progressed, because of the cellularization of the three-dimensional structure. In conclusion, multiscale scaffolds could exhibit a suitable behavior as a bioactive small-diameter vascular implant.

Development of endomyocardial fibrosis model using a cell patterning technique: In vitro interaction of cell coculture of 3T3 fibroblasts and RL-14 cardiomyocytes.

Cardiac functions can be altered by changes in the microstructure of the heart, i.e., remodeling of the cardiac tissue, which may activate pathologies such as hypertrophy, dilation, or cardiac fibrosis. Cardiac fibrosis can develop due to an excessive deposition of extracellular matrix proteins, which are products of the activation of fibroblasts. In this context, the anatomical-histological change may interfere with the functioning of the cardiac tissue, which requires specialized cells for its operation. The purpose of the present study was to determine the cellular interactions and morphological changes in cocultures of 3T3 fibroblasts and RL-14 cardiomyocytes via the generation of a platform an in vitro model. For this purpose, a platform emulating the biological characteristics of endomyocardial fibrosis was generated using a cell patterning technique to study morphological cellular changes in compact and irregular patterns of fibrosis. It was found that cellular patterns emulating the geometrical distributions of endomyocardial fibrosis generated morphological changes after interaction of the RL-14 cardiomyocytes with the 3T3 fibroblasts. Through this study, it was possible to evaluate biological characteristics such as cell proliferation, adhesion, and spatial distribution, which are directly related to the type of emulated endomyocardial fibrosis. This research concluded that fibroblasts inhibited the proliferation of cardiomyocytes via their interaction with specific microarchitectures. This behavior is consistent with the histopathological distribution of cardiac fibrosis; therefore, the platform developed in this research could be useful for the in vitro assessment of cellular microdomains. This would allow for the experimental determination of interactions with drugs, substrates, or biomaterials within the engineering of cardiac tissues.