Abstract

Regenerative medicine involves methods to control and modify normal tissue repair processes. Polymer and cell constructs are under research to create tissue that replaces the affected area in cardiac tissue after myocardial infarction (MI). The aim of the present study is to evaluate the behavior of differentiated and undifferentiated mesenchymal stem cells (MSCs) in vitro and in silico and to compare the results that both offer when it comes to the design process of biodevices for the treatment of infarcted myocardium in biomodels. To assess in vitro behavior, MSCs are isolated from rat bone marrow and seeded undifferentiated and differentiated in multiple scaffolds of a gelled biomaterial. Subsequently, cell behavior is evaluated by trypan blue and fluorescence microscopy, which showed that the cells presented high viability and low cell migration in the biomaterial. An agent-based model intended to reproduce as closely as possible the behavior of individual MSCs by simulating cellular-level processes was developed, where the in vitro results are used to identify parameters in the agent-based model that is developed, and which simulates cellular-level processes: Apoptosis, differentiation, proliferation, and migration. Thanks to the results obtained, suggestions for good results in the design and fabrication of the proposed scaffolds and how an agent-based model can be helpful for testing hypothesis are presented in the discussion. It is concluded that assessment of cell behavior through the observation of viability, proliferation, migration, inflammation reduction, and spatial composition in vitro and in silico, represents an appropriate strategy for scaffold engineering.

Highlights

  • Cardiovascular diseases are a public health problem that represents 30% of the world mortality

  • Our study aims at identifying the behavior of rat Mesenchymal Stem Cells (MSCs) in a collagen scaffold, regarding viability and migration, to generate an agent-based model able to give information about the viability of the cells after a certain period of time, the differentiation of mesenchymal stem cells (MSCs), and how the cells might arrange over the myocardial tissue

  • This study was developed as part of the project “Design and construction of a scaffold from a biomaterial that serves as support for mesenchymal stem cells (MSC) of pig bone marrow, for its potential use in the regeneration of the infarcted myocardium of a biomodel” of the Tissue Engineering Research Seeding Group and the Additive Manufacturing Research Seeding Group of Autónoma de Occidente University (Colombia)

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Summary

Introduction

Cardiovascular diseases are a public health problem that represents 30% of the world mortality. MI is one of the five main expressions of coronary disease, which implies an obstruction in the blood flow due to the presence of plaques in the coronary arteries that causes myocardial cell necrosis due to. The failure of current treatments to restore completely the functional myocardium [1] has led to a search for new strategies in tissue engineering through cell therapy by stimulating endogenous regenerative mechanisms of the body. The interaction of a cell source and a biopolymeric material, known as a scaffold, is considered a compelling candidate in tissue regeneration to optimize cell development in the injured area [2]. Scaffolds should exhibit very precise properties such as elasticity matching the myocardium, host cell integration and vascularization, mechanical stability, and non-immunogenicity to support tissue function and regeneration [3]

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