A defined road to tracheal reconstruction: laser structuring and cell support for rapid clinic translation.

One of the severe complications occurring because of the patient's intubation is tracheal stenosis. Its incidence has significantly risen because of the COVID-19 pandemic and tends only to increase. Here, we propose an alternative to the donor trachea and synthetic prostheses-the tracheal equivalent. To form it, we applied the donor trachea samples, which were decellularized, cross-linked, and treated with laser to make wells on their surface, and inoculated them with human gingiva-derived mesenchymal stromal cells. The fabricated construct was assessed in vivo using nude (immunodeficient), immunosuppressed, and normal mice and rabbits. In comparison with the matrix ones, the tracheal equivalent samples demonstrated the thinning of the capsule, the significant vessel ingrowth into surrounding tissues, and the increase in the submucosa resorption. The developed construct was shown to be highly biocompatible and efficient in trachea restoration. These results can facilitate its clinical translation and be a base to design clinical trials.

A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy.

Cardiovascular diseases associated with high cholesterol (hypercholesterolemia) and low-density lipoproteins (LDL) levels are significant contributors to total mortality in developing and developed countries. Mathematical modeling of LDL metabolism is an important step in the development of drugs for hypercholesterolemia. The aim of this work was to develop and to analyze an integrated mathematical model of cholesterol metabolism in liver cells and its interaction with two types of drugs, statins and PCSK9 inhibitors. The model consisted of 21 ordinary differential equations (ODE) describing cholesterol biosynthesis and lipoprotein endocytosis in liver cells in vitro. The model was tested for its ability to mimic known biochemical effects of familial hypercholesterolemia, statin therapy, and PCSK9 inhibitors. The model qualitatively reproduced the well-known biology of cholesterol regulation, which confirms its potential for minimizing cellular research in initial testing of new drugs for cardiology.