Chitosan-Based Scaffolds for the Treatment of Myocardial Infarction: A Systematic Review

Abstract

Cardiovascular diseases (CVD), such as myocardial infarction (MI), constitute one of the world's leading causes of annual deaths. This cardiomyopathy generates a tissue scar with poor anatomical properties and cell necrosis that can lead to heart failure. Necrotic tissue repair is required through pharmaceutical or surgical treatments to avoid such loss, which has associated adverse collateral effects. However, to recover the infarcted myocardial tissue, biopolymer-based scaffolds are used as safer alternative treatments with fewer side effects due to their biocompatibility, chemical adaptability and biodegradability. For this reason, a systematic review of the literature from the last five years on the production and application of chitosan scaffolds for the reconstructive engineering of myocardial tissue was carried out. Seventy-five records were included for review using the "preferred reporting items for systematic reviews and meta-analyses" data collection strategy. It was observed that the chitosan scaffolds have a remarkable capacity for restoring the essential functions of the heart through the mimicry of its physiological environment and with a controlled porosity that allows for the exchange of nutrients, the improvement of the electrical conductivity and the stimulation of cell differentiation of the stem cells. In addition, the chitosan scaffolds can significantly improve angiogenesis in the infarcted tissue by stimulating the production of the glycoprotein receptors of the vascular endothelial growth factor (VEGF) family. Therefore, the possible mechanisms of action of the chitosan scaffolds on cardiomyocytes and stem cells were analyzed. For all the advantages observed, it is considered that the treatment of MI with the chitosan scaffolds is promising, showing multiple advantages within the regenerative therapies of CVD.

Keywords: biopolymers; cardiac tissue engineering; chitosan scaffolds; heart attack; natural polysaccharide.

Figure 3

(A) Chemical structure of chitosan. (B) Synthetic methods commonly used for functionalizing chitosan in tissue engineering: alkylation [121], O-alkylation [115], N-acetylation [115], phosphorylation [122] and crosslinking [123]. Reactive functional groups of chitosan: Magenta box, hydroxyl at C-6. Cyan box, C-3 hydroxyl. Red circle, primary amine at C-2. Abbreviations: rGO = reduced graphene oxide, TAC = tannic acid, PVA = polyvinyl alcohol, ECH = epichlorohydrin, HOAc = acetic acid.

Figure 1

PRISMA 2020 methodology [36] was used to search for the information.

Figure 2

Graphic representation of myocardial infarction; (a) non-transmural and transmural myocardial infarction, (b) the formation of the infarcted tissue in the heart after an ischemic process. (1) Cell death in the first hours of infarction. (2) Cytokine release and degradation of the necrotic cells by macrophages. (3) Muscle fibrosis processes due to a high protein content in the infarcted area and dysfunctional cell degradation. (4) Final fabric. Abbreviations: ECM, extracellular matrix; BMs, biomarkers; CMs, cardiomyocytes; NSTEMI, non-T-segment elevation myocardial infarction; STEMI, T-segment elevation myocardial infarction; EGC, electrocardiogram [38,44].

Figure 2

Graphic representation of myocardial infarction; (a) non-transmural and transmural myocardial infarction, (b) the formation of the infarcted tissue in the heart after an ischemic process. (1) Cell death in the first hours of infarction. (2) Cytokine release and degradation of the necrotic cells by macrophages. (3) Muscle fibrosis processes due to a high protein content in the infarcted area and dysfunctional cell degradation. (4) Final fabric. Abbreviations: ECM, extracellular matrix; BMs, biomarkers; CMs, cardiomyocytes; NSTEMI, non-T-segment elevation myocardial infarction; STEMI, T-segment elevation myocardial infarction; EGC, electrocardiogram [38,44].

Figure 4

(A) Elaboration of the scaffold, constituents and uses. (B) Possible mechanism of cellular regeneration and differentiation of the cardiomyocytes. The chitosan scaffold allows for the transfer of exogenous cells to the damaged tissue. In the process, the scaffold surface mechanically stimulates the VEGFRs. Simultaneously, the VEGFR can be electrically stimulated by natural electrical stimuli from the heart or external sources due to the functionalization of chitosan with the other electro-conductive polymers (represented in the figure as R). This electrical stimulation helps the release of the VEGF, the differentiation of the stem cells to the native cardiomyocytes or the differentiation to the endothelial cells in the angiogenesis processes, improving the hemodynamic processes of the heart, cell replacement and ventricular thickening of the heart. Abbreviations, NHAc = acetylated amino group, NHR = functionalized amino group.

Figure 4

(A) Elaboration of the scaffold, constituents and uses. (B) Possible mechanism of cellular regeneration and differentiation of the cardiomyocytes. The chitosan scaffold allows for the transfer of exogenous cells to the damaged tissue. In the process, the scaffold surface mechanically stimulates the VEGFRs. Simultaneously, the VEGFR can be electrically stimulated by natural electrical stimuli from the heart or external sources due to the functionalization of chitosan with the other electro-conductive polymers (represented in the figure as R). This electrical stimulation helps the release of the VEGF, the differentiation of the stem cells to the native cardiomyocytes or the differentiation to the endothelial cells in the angiogenesis processes, improving the hemodynamic processes of the heart, cell replacement and ventricular thickening of the heart. Abbreviations, NHAc = acetylated amino group, NHR = functionalized amino group.