ABSTRACT
Myocardial Infarction (MI) is a leading cause of death worldwide. Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling after MI. However, whether material-derived cues can treat MI through metabolic regulation is mainly unexplored. Herein, a Cu2+ loaded casein microgel (CuCMG) aiming to rescue the pathological intramyocardial metabolism for MI amelioration is developed. Cu2+ is an important ion factor involved in metabolic pathways, and intracardiac copper drain is observed after MI. It is thus speculated that intramyocardial supplementation of Cu2+ can rescue myocardial metabolism. Casein, a milk-derived protein, is screened out as Cu2+ carrier through molecular-docking based on Cu2+ loading capacity and accessibility. CuCMGs notably attenuate MI-induced cardiac dysfunction and maladaptive remodeling, accompanied by increased angiogenesis. The results from unbiased transcriptome profiling and oxidative phosphorylation analyses support the hypothesis that CuCMG prominently rescued the metabolic homeostasis of myocardium after MI. These findings enhance the understanding of the design and application of metabolic-modulating biomaterials for ischemic cardiomyopathy therapy.
ABSTRACT
Ischemic cardiomyopathy (ICM) affect millions of patients globally. Decellularized extracellular matrix materials (dECM) have components, microstructure and mechanical properties similar to healthy cardiac tissues, and can be manufactured into various forms of implantable biomaterials including injectable hydrogels or epicardial patches, which have been extensively reported to attenuate pathological left ventricular remodeling and maintain heart function. Recently, dECM medical devices for ICM treatment have been approved for clinical use or studied in clinical trials, exhibiting considerable translation potential. Cells, growth factors and other bioactive agents have been incorporated with different dECM materials to improve the therapeutic outcomes. In addition, more detailed aspects of the biological effects and mechanisms of dECM treatment are being revealed. This review summarized recent advances in dECM materials from variable sources for cardiac repair, including extraction of extracellular matrix, cell integration, smart manufacturing of injectable hydrogels and cardiac patch materials, and their therapeutic applications. Besides, this review provides an outlook on the cutting-edge development directions in the field.
