Collagen Hydrogel Containing Polyethylenimine‐Gold Nanoparticles for Drug Release and Enhanced Beating Properties of Engineered Cardiac Tissues

Abstract

AbstractCardiac tissue engineering is a promising strategy to prevent heart failure. However, several issues remain unsolved, including efficient electrical coupling and incorporating factors to enhance tissue maturation and vascularization. Herein, a biohybrid hydrogel that enhances beating properties of engineered cardiac tissues and allows drug release concurrently is developed. Gold nanoparticles (AuNPs) with different sizes (18–241 nm) and surface charges (33.9–55.4 mV) are synthesized by reducing gold (III) chloride trihydrate using branched polyethyleneimine (bPEI). These nanoparticles increase gel stiffness from ≈91 to ≈146 kPa, enhance electrical conductivity of collagen hydrogels from ≈40 to 49–68 mS cm−1, and allow slow and steady release of loaded drugs. Engineered cardiac tissues based on bPEI‐AuNP‐collagen hydrogels and either primary or human induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes show enhanced beating properties. hiPSC‐derived cardiomyocytes exhibit more aligned and wider sarcomeres in bPEI‐AuNP‐collagen hydrogels compared to collagen hydrogels. Furthermore, the presence of bPEI‐AuNPs result in advanced electrical coupling evidenced by synchronous and homogenous calcium flux throughout the tissue. RNA‐seq analyses are in agreement with these observations. Collectively, this data demonstrate the potential of bPEI‐AuNP‐collagen hydrogels to improve tissue engineering approaches to prevent heart failure and possibly treat diseases of other electrically sensitive tissues.