Regeneration of infarcted hearts by myocardial infarction-responsive injectable hydrogels with combined anti-apoptosis, anti-inflammatory and pro-angiogenesis properties

Abstract

Current treatments including drug therapy, medical device implantation, and organ transplantation have considerable shortcomings for myocardial infarction (MI), such as high invasiveness, the scarce number of donor organs, easy thrombosis, immune rejection, and poor therapeutic effects. Therefore, the development of new solutions to repair infarcted hearts is urgently needed. Smart responsive injectable hydrogels have served as a good foundation in biomedical engineering, especially for cardiac regeneration. Herein, we synthesized an injectable hydrogel that responds to the inflammatory microenvironment at the site of MI to provide the drug curcumin (Cur) and tailored recombinant humanized collagen type III (rhCol III) in a controlled manner for myocardial repair. The excellent antioxidant and anti-inflammatory properties of Cur could effectively reduce the ROS level and cell apoptosis and inhibit inflammatory reactions after MI. The tailored rhCol III promoted cell proliferation, migration, and angiogenesis. The therapeutic hydrogel resulted in the rapid recovery of cardiac function after MI by elevating the expression of the cardiac markers α-actinin and CX 43. In vitro and in vivo data showed that the combined anti-apoptosis, anti-inflammatory and pro-angiogenesis treatment strategies were an auspicious tactic for the treatment of MI, and had significant clinical application value. Furthermore, the work also demonstrated the great application potential of our tailored rhCol III in promoting the repair and regeneration of infarcted hearts.