One Zwitterionic Injectable Hydrogel with Ion Conductivity Enables Efficient Restoration of Cardiac Function after Myocardial Infarction

Abstract Conventional strategies for constructing an injectable conductive hydrogel for treatment of myocardial infarction (MI) are mostly involved with complicated bioactive modification and incorporation of external conductive materials and cells/therapeutic drugs, severely restraining its medical translation. Herein, a cell-free and therapeutic drug-free injectable zwitterionic hydrogel is fabricated by thiol-acrylate Michael addition reaction between acrylate modified polycarboxybetaine macromonomer and dithiothreitol (DTT), where the free DTT and the tethered-DTT endow the hydrogel with an antioxidant ability. The zwitterionic hydrogel is optimized to exhibit an appropriate gelation time and injectability. Intriguingly, the cation-anion ion pair on the side chain affords an intrinsic conductive property similar to the native myocardium. After injection into the infarcted region of rats, the hydrogel can downregulate level of inflammatory factors, and upregulate the expressions of cardiac-related factors, angiogenic factors, and transmission electrical signal-relevant Cx-43, accompanied by suppression of oxidant stress and cardiac fibrosis and increased vessel density, supposedly due to inherent antifouling, vascularization-promoting and conductive properties. Echocardiography and histological analyses demonstrate a remarkable improvement of the functions and structure of infarcted myocardium in rats in terms of 2.17/2.80-fold increase in ejection fraction/fractional shortening, 3.62-fold decline in end-systolic volume, and 2.39-fold decrease in fibrosis area, compared to MI group. This cell-free and therapeutic drug-free injectable zwitterionic hydrogel represents a new approach to seek a simplified but holistic biomaterial for treating myocardial infarction.