Biocompatibility Assessment of an Injectable Carbon Nanotube-Functionalized Reverse Thermal Gel for Cardiac Tissue Engineering Applications.

Heart failure (HF) is a major contributor to the global burden of cardiovascular disease. Current treatments for HF do not regenerate or restore cardiac muscle function, leaving cardiac transplantation as the only definitive treatment for end-stage HF. Subsequently, there is a tremendous need for alternative HF treatments as well as methods to effectively and selectively deliver those therapies to the heart. We have engineered an injectable reverse thermal gel (RTG) functionalized with carbon nanotubes (CNTs) to create a thermoresponsive conductive hydrogel or RTG-CNT. The RTG-CNT transitions from a liquid solution to a gel-based matrix upon reaching body temperature, a unique quality that allows for rapid injection of the liquid polymeric solution followed by gel localization in situ. Previously, we demonstrated the potential use of the RTG-CNT hydrogel for cardiac tissue engineering applications using three-dimensional (3D) cocultures of primary cardiac cells. Here, we performed a preclinical study to assess the biocompatibility of our RTG-CNT hydrogel in vivo by using hydrogel intracardial injection in a mouse model and in vitro by using 3D cultures of human-induced pluripotent stem cell-derived cardiomyocytes. In this report, we present compelling results that demonstrate the RTG-CNT hydrogel biocompatibility and its potential for use in cardiac tissue engineering applications.