DELIVERY OF BIOMATERIALS WITH CYTOKINES AND GROWTH FACTORS FOR MYOCARDIAL INFARCTION TREATMENT

Abstract

One of the crucial and highly specialized organs in the human body is heart. It has limited regenerative and self-healing potential after the event of injury or illness. Therefore, heart transplantation is the primary treatment for end-stage cardiovascular disorders at the moment. Cardiovascular disease, particularly ischemic heart disease, continues to be one of the main causes of mortality worldwide. After a heart attack, the injured cardiomyocytes are lost and replaced with fibrotic scar tissue (Hashimoto et al., 2018). Cardiomyocyte loss has several consequences, for instance, the reduction of ventricular contraction, which triggers more cardiomyocyte loss, pathological cardiac dilatation, and ultimately heart failure. These series of events fall under the term “cardiac remodeling” (Tenreiro et al., 2021). The main objective of many treatments has been to prevent the gradual cardiac remodeling that leads to heart failure. Currently available effective treatments are medications, coronary artery bypass grafting, percutaneous coronary intervention and heart transplantation (Head et al., 2018). This paper aims to describe a treatment protocol that includes the sequential administration of a composite cryogel with specific cytokines and growth factors. Firstly, the cryogel containing interleukin-10 (IL-10) was directly injected intramyocardially immediately after the induction of myocardial infarction, with the aim to target the acute inflammatory response. A second injection of cryogel loaded with vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) was done on day 7 post-MI. The purpose of the second injection was to stimulate tissue regeneration and the formation of new blood vessels (neoangiogenesis). In the cohort treated with Cryogel/GF, the study’s results demonstrated significant myocardial tissue regeneration. Masson’s Trichrome staining verified the echocardiographic findings, which showed decreased fibrotic areas and increased ejection fraction as well as fractional shortening. Therefore, the newly-developed chitosan-based cryogel contains anti-inflammatory and proangiogenic components, making this biomaterial an excellent cargo for the controlled release of therapeutic factors. Consequently, this will significantly improve tissue regeneration post-myocardial infarction.

Hypothesis: cryogel containing IL-10 cytokine and VEGF/FGF-2 growth factors delivered sequentially will improve cardiac regeneration after MI.