Electroactive biomaterials synergizing with electrostimulation for cardiac tissue regeneration and function-monitoring

Cardiac cells are assembled within a complicated microenvironment possessing diverse biochemical and biophysical cues that modulate cellular behaviors and tissue functions. Apart from the widely studied pathways of biochemical regulation, positive effects of electrical cues on the regeneration of excitable cardiac tissues have been demonstrated. Conductive biomaterials have emerged as important two-way media to facilitate the transmission of endogenous bioelectricity or exogenous electrical stimuli strengthening cardiac tissue regeneration, while in the meantime allow online monitoring of bioelectrical activities. Mechanical energy exists prevalently in the heart, which brings huge promise in building a self-powered, monitoring enabled, on-demand stimulation system by using piezoelectric biomaterials. In this regard, conductive biomaterials and piezoelectric biomaterials synergizing with electrostimulation for tissue regeneration and function-monitoring in cardiac tissue engineering are comprehensively reviewed. After the biological electrical conduction system in the human heart is firstly introduced, electroactive biomaterials that display biomimetic microenvironmental cues (e.g., electrical, mechanical, topological) and their mediated electrostimulation are summarized. Subsequently, the current state in electroactive biomaterials synergizing with electrostimulation for cardiac tissue regeneration is systematically overviewed together with the underlying mechanisms in modulating cardiac cell activities. Furthermore, recent advances in electroactive biomaterials used in the online monitoring of cardiac tissue function are discussed. Finally, the remaining challenges in 3D complex biomimetic designs, systematic parameter optimizations and cellular mechanisms, long-term electrical performance, and biosafety are laid out, which call for interdisplinary joint forces in the innovation and advancement.