Facile pH-responsive injectable polyphenol-europium assembly coordination complex with enhanced antioxidation and angiogenesis for myocardial infarction treatment

Abstract

In situ injectable biomaterials for cardiac tissue regeneration are a promising therapeutic strategy for progressive heart failure following myocardial infarction (MI). Herein, a pH-responsive injectable coordination complex is devised with a green method by facile tannic acid (TA)-europium ion (Eu3+) assembly at room temperature, which have enhanced antioxidation and angiogenesis for treating myocardial infarction (MI). The physicochemical characterization indicates that the TA and Eu3+ are assembled with a relatively uniform size (30–100 μm). In vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant tests display good antioxidant ability (93.43% DPPH scavenging). The resulting TA/Eu coordination complex (TA/Eu CPs) exhibit sustained release of tannic acid and Eu3+ at acidic pH, which conducive to MI treatment (acidic microenvironment, pH < 6.8). Cytocompatibility experiments illustrate that injectable TA/Eu CPs can promote the adhesion and proliferation of human umbilical vein endothelial cells (HUVECs), and have no cytotoxicity for H9c2 cells. Meanwhile, TA/Eu CPs could promote the HUVECs to form capillaries in vitro. Besides, real-time quantitative PCR (RT-qPCR) and western blot assays illustrate that it can stimulate proangiogenesis by elevating the expression of angiogenesis-related genes and proteins. In vivo Sprague-Dawley (SD) rats experiments indicate that TA/Eu CPs have no in vivo immunogenicity. Most importantly, SD rats MI experiment demonstrates a significant functional improvement, such as infarct size reducing, neovascularization increasing and inhibiting inflammatory responses. Overall, the TA/Eu3+ coordination complex can act as a functional material for MI treatment.