3D Printable and Electrically Conductive Hyaluronic Acid Hydrogel for Cardiac and Vascular Tissue Engineering Applications

Cardiovascular disease (CVD) is the leading cause of death worldwide. After acute myocardial infarction (AMI), the adult human heart has very limited regenerative capacities, and the electrical propagation of the myocardium is severely disrupted, which makes the patient more susceptible to heart failure and death. Current pharmaceutical treatments do not address the loss of cardiomyocytes (CMs) or the disruption of electrical propagation in the heart. Tissue engineering provides a potential solution with electrically conductive hydrogels that are biocompatible to promote CM viability, lineage-specific function, and vascularization while helping reestablish the electrical propagation of native myocardium. Incorporating patient-specific CMs and automated, rapid 3D printing techniques will improve the clinical translation of these engineered tissues for the repair of damaged myocardium. To address these limitations, we developed a novel, electrically conductive, photocurable, and 3D-printable hydrogel composed of methacrylated hyaluronic acid (MeHA) conjugated with 3-thiopheneacetic acid (3TAA) in deionized water. This novel, multifunctional hydrogel significantly increased electrical conductivity compared to MeHA alone, although a decrease in average storage modulus was observed with the 3TAA conjugation. Biocompatibility assessment demonstrated sustained cardiac and vascular cell activity in both MeHA and MeHA 3TAA hydrogels. Notably, CMs derived from human-induced pluripotent stem cells (hiPSCs) retained the expression of the cardiac biomarker CTnT and maintained spontaneous beating within MeHA and MeHA 3TAA hydrogels.