Injectable Reverse Thermal Gel Biopolymers may Act as an Extracellular Matrix and Cell Vehicle for Cardiac Tissue Engineering

Abstract

Background: Recent investigations demonstrated that tissue engineering represents a promising strategy to repair diseased hearts. We hypothesized that temperature-responsive materials could be developed as extracellular matrix scaffolds and cell delivery vehicles could be used in cardiac tissue engineering.Methods and results: We developed injectable reverse thermal gel (RTG) biopolymers that are designed to transition from low viscous liquid to a solid gel by exposure to body temperature. This allows deployment through a small gauge needle to the target area with minimal surgical intervention. For this study we tested different RTG biopolymers with and without chemical incorporation of laminin. In vitro 3D culture experiments were performed with adult rat ventricular myocytes (ARVM) by mixing 3x103 cells with 50 μl of liquid-phase polymeric solution (25°C) and permitting transition to a gel at 37°C. These cultured cells were incubated 8 days in the gel matrix. As controls, ARVMs were plated on 2D traditional laminin coated dishes. Compared to control groups, we found that the 3D matrix improved ARVM viability: after 3 days of culture, ARVM viability increased by 27% and 17% in the RTG-laminin and in the RTG, respectively. At the 8th day of culture, 63% of the ARVMs in the RTG-laminin group were rod shaped and viable, while in RTG and control groups, most of the ARVMs were round shaped and non-viable.Conclusion: These preliminary proof-of-concept results demonstrate excellent cell viability in the RTG-laminin biopolymer for up to 8 days and show feasibility of a novel cell delivery system that permits reversible liquid-to-gel transition from room to body temperature. This holds tremendous potential for cardiac tissue engineering.