An injectable multicomponent integrated microgel promotes cardiomyocyte regeneration and heart function after ischemia reperfusion injury

Abstract

Myocardial ischemia reperfusion (I/R) injury frequently impacts the outcome of patients with coronary heart disease and lacks effective therapeutic strategies. We have summarized the challenges in treating IR injury into three aspects, namely inflammatory reaction, fibrosis, and impaired proliferation ability of myocardial tissue. To address these issues, we have developed an injectable composite microgel called DMP@mgel by integrating three types of biomaterials: placental-derived mesenchymal stem cells loaded microgel, PEDOT:PSS loaded microgel, and siRNA-loaded carrier DP7-C. Upon injection into the injured area, DMP@mgel could regulate the inflammatory microenvironment, promote angiogenesis by the function of stem cells paracrine. Additionally, it enhances coupling between myocardial cells due to its high electrical conductivity. Moreover, DP7-C/siRNA complex can efficiently transfect into myocardial cells to inhibit Hippo pathway activity and promote cell proliferation. The electrostatic interaction enables DP7-C to combine all components into a stable delivery system. In vitro and in vivo experiments confirmed that each ingredient of DMP@mgel exhibits their respective functions such as neovascularization promotion, Hippo pathway inhibition, and antioxidation capability. Finally, administration of DMP@mgel in I/R injured rats significantly improved heart function while reducing fibrosis as evidenced by echocardiography results along with Evans blue staining and histological examination.