A composite conductive hydrogel loaded with alginate/gelatin microspheres with micro-environmentally induced smart temporal regulation for acute myocardial infarction treatment

Designing a temporal regulation system for responsive stem cell delivery that simultaneously addresses micro-environmental improvement in the infarcted area and electromechanical coupling compensation through synergistic stem cell therapy continues to pose substantial research challenges. We present a micro-environmentally induced smart temporal regulation composite conductive hydrogel for myocardial infarction therapy. Adipose derived stem cells (ADSC) were seeded on alginate (Alg)/gelatin (GT) composite microspheres (Alg/GT), which were encapsulated into reactive oxygen species (ROS) responsive conductive hydrogels (HGB) based on hyaluronic acid functionalized with phenylboronic acid (HA-PBA), dopamine-modified GT (GT-DA), and borate-functionalized polyaniline (BPA). Alg/GT microspheres exhibit excellent carrying capacity for ADSC and promoting ADSC paracrine effects. Besides the smart controlled release properties, the optimised hydrogel (HGB3) possesses a variety of functional properties including injectability, appropriate mechanical strength and electrical conductivity, anti-inflammatory and antioxidant properties. Together, these properties contribute to micro-environmental enhancement and electromechanical coupling restoration in the infarcted myocardial region. When the composite system was injected into the infarcted myocardifm, it achieved benign remodeling of the infarcted myocardium through regulation of inflammation, inhibition of fibrosis and promotion of vascular regeneration. This micro-environmentally induced smart temporal regulation composite conductive hydrogel system offers a novel therapeutic strategy for the management of acute myocardial infarction.