Stem cell-loaded adhesive immiscible liquid for regeneration of myocardial infarction

Myocardial infarction (MI) causes serious loss of cardiac muscle and dysfunction. To restore MI, exogenous stem cells should be efficiently delivered. However, due to severe physical and physiological cardiac environment, recent strategies have faced challenges, including low cell persistence, low integration, and delayed therapeutic effects. Herein, we proposed mesenchymal stem cell (MSC) therapeutic platform using adhesive protein-based immiscible condensed liquid system (APICLS) derived from bioengineered mussel adhesive protein (MAP). With high encapsulation efficiency and survival rate of encapsulated MSCs, APICLS was successfully grafted by intramyocardial injection and distributed throughout the scarred myocardium. Its underwater adhesiveness and biocompatibility fostered integration with damaged tissue, resulting in high cell persistence and maximized paracrine effects. Bioactive molecules released from APICLS with MSCs induced angiogenesis and cardioprotection, delayed cardiac remodeling, reduced fibrosis, and recovered contractive force. Thus, our proposed strategy represents an innovative approach for recovering infarcted cardiac tissues with damaged structural and contractive function. The unique physiochemical properties of APICLS allow transplanted MSCs to stably remain and to be rapidly integrated at the injected site, resulting in enhanced therapeutic efficacy through maximized paracrine effects. [Display omitted] •Fluid-immiscible sticky platform helps prolonged cell retention in harsh condition.•Surviving cells regenerate infarcted myocardium with maximized paracrine effect.•This study suggests a promising assessment for direct stem cell injection strategy.