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

Cardiac tissue engineering is a promising strategy to prevent heart failure. However, several issues remain to be solved, including efficient electrical coupling and incorporating factors to enhance tissue maturation and vascularization. Here, we developed a biohybrid hydrogel that enhances beating properties of engineered cardiac tissues and allows drug release concurrently. We synthesized gold nanoparticles (AuNPs) with different sizes (18 - 241 nm) and surface charges (33.9 - 55.4 mV) by reducing gold (III) chloride trihydrate using branched polyethyleneimine (bPEI). These nanoparticles increased gel stiffness from ∼91 to ∼146 kPa, enhanced electrical conductivity of collagen hydrogels from ∼40 to 49 - 68 mS/cm, and allowed a slow and steady release of loaded drugs. Engineered cardiac tissues based on bPEI-AuNP-collagen hydrogels and either primary or hiPSC-derived cardiomyocytes showed enhanced beating properties. hiPSC-derived cardiomyocytes exhibited more aligned and wider sarcomeres in bPEI-AuNP-collagen hydrogels compared to collagen hydrogels. Furthermore, the presence of bPEI-AuNPs resulted in advanced electrical coupling evidenced by synchronous and homogenous calcium flux throughout the tissue. RNA-seq analyses were in agreement with these observations. Collectively, our 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. This article is protected by copyright. All rights reserved.