A four-in-one multifunctional self-assembly hydrogel composed of natural drugs for repairing myocardial infarction

To meet the multiple demands of myocardial repair, it would be a novel strategy for myocardial repair if multiple drugs could be constructed into an integrated multifunctional drug formulation. In this study, four drugs with different functions (thioctic acid with antioxidant effects, quercetin with anti-inflammatory and antioxidant effects, arginine with pro-angiogenic effects, and Mn2+ with imaging functions) were selected to construct a four-in-one injectable hydrogel (thioctic acid-arginine-quercetin-Mn2+) through chemical bonding and supramolecular interactions. First, thioctic acid polymerized to a redox-sensitive degradable polymer—poly(thioctic acid) containing disulfide bonds in the main chains through ring-opening polymerization. Quercetin was conjugated to the main chain of the poly(thioctic acid) molecules via thiyl radical-polyphenol Michael addition. Arginine cross-linked the carboxyl groups side chains of the poly(thioctic acid) molecules through hydrogen bonding. Mn2+ further cross-linked the carboxyl groups' side chains of the poly(thioctic acid) molecules through ionic bonding. The hydrogel has antioxidant properties, promotes neovascularization, inhibits inflammatory, improves intracellular Ca2+ overload and mitochondrial dysfunction, protects adenosine triphosphatase (ATPase) activity, and maintains intracellular energy supply, which can reduce the size of myocardial infarcts, and improves cardiac function. This construction method of preparing integrated multifunctional hydrogels from natural drugs will provide a new therapeutic strategy for myocardial repair.