C oronary heart disease is the leading cause of the rising incidence of heart failure worldwide.1 Following myocardial infarction (MI), the limited regenerative potential of the heart causes scar formation in and around the infarction, leading to abnormal electric signal propagation and desynchronized cardiac activation and contraction.2 The lack of electric connection between healthy myocardium and the scar with its islands of intact cardiomyocytes contributes to progressive functional decompensation. Injectable biomaterial has shown promise as an alternative biological treatment option after MI to reduce adverse remodeling and preserve cardiac function.3,4 Among their many advantages, injectable materials can be delivered alone or as a vehicle carrying combination therapies, including cells or growth factors, and may provide mechanical and functional support to the injured heart. Over the past decade, several injectable biomaterials such as collagen, 5,6 alginate, 7 and fibrin 8 have been extensively studied. Organic polymers that conduct electricity (conductive polymers) were first described in 1977, and this discovery was awarded the Nobel prize in 2000.9,10 Conductive polymers are particularly appealing because they exhibit electric properties similar to metals and semiconductors while retaining flexibility, ease of processing, and modifiable conductivity. The electric properties of these materials can be fine-tuned by altering their synthetic processes, including the addition of specific chemical agents.11 Biological applications of conductive polymersBackground-Efficient cardiac function requires synchronous ventricular contraction. After myocardial infarction, the nonconductive nature of scar tissue contributes to ventricular dysfunction by electrically uncoupling viable cardiomyocytes in the infarct region. Injection of a conductive biomaterial polymer that restores impulse propagation could synchronize contraction and restore ventricular function by electrically connecting isolated cardiomyocytes to intact tissue, allowing them to contribute to global heart function. Methods and Results-We created a conductive polymer by grafting pyrrole to the clinically tested biomaterial chitosan to create a polypyrrole (PPy)-chitosan hydrogel. Cyclic voltammetry showed that PPy-chitosan had semiconductive properties lacking in chitosan alone. PPy-chitosan did not reduce cell attachment, metabolism, or proliferation in vitro. Neonatal rat cardiomyocytes plated on PPy-chitosan showed enhanced Ca 2+ signal conduction in comparison with chitosan alone. PPy-chitosan plating also improved electric coupling between skeletal muscles placed 25 mm apart in comparison with chitosan alone, demonstrating that PPy-chitosan can electrically connect contracting cells at a distance. In rats, injection of PPy-chitosan 1 week after myocardial infarction decreased the QRS interval and increased the transverse activation velocity in comparison with saline or chitosan, suggesting improved electric conduction. Optical mapping showed incr...