Use of patches of collagen-fibroin silk-alginate sodium-carboximethyl cellulose associated with mesenchimal stem cells for myocardial regeneration and remodeling on infarted area: experimental study in rats

Abstract

Ischemic heart disease is a common condition worldwide. The intervention with patch application on the injured surface has been explored as a possible treatment. Currently, therapies such as percutaneous myocardial revascularization are often not fully effective and most patients develop cardiomyopathies and heart failure as a result of the unfavorable cardiac remodeling process. Moreover, the low number of younger stem cells capable of differentiating over the heart encumbers myocardial regeneration. The application of biodegradable scaffolds associated with stem cells over the infarcted area provides mechanical support to the left ventricle and it can influence myocardial remodeling. This study aims to analyze the application of biomaterials in hearts post-myocardial infarction rat hearts and verify which of the applied materials achieved the best performance. Rats will undergo myocardial infarction and after two weeks, patches made of collagen and silk fibroin or printed nanocomposite hydrogels of biocompatible polymers and cellulose nanocrystals (CMC) will be sutured to the infarcted myocardium. Both patches will be seeded with MSCs-AT. They will be periodically assessed by echocardiography and after eight weeks, will be sacrificed and hearts will be harvested. Hearts will be perfused on the "isolated heart" Langendorf apparatus and posteriorly assessed by histology for measurements of proportional infarct size and ventricular thickness. Samples of heart tissue will be isolated for measuring TNF and interleukins by Western Blotting. Blood and tissue samples will be collected for haematologic and oxidative analysis to analyze the security of the biomaterials. We expect to observe improvement in ventricular remodeling-related end-points and correlate them to MSCs-AT. The verification of which association of biomaterials to cellular components correlates to the best results in the rat model will lead to selecting it to be applied in a similar infarct model in swine or clinical translation in the future.(AU)