Rational design of electrically conductive biomaterials toward excitable tissues regeneration

Cells in vivo are situated in a complicated microenvironment composed of diverse biochemical and biophysical cues. To regulate biological functions of cells, tissues and organs bioelectricity (i.e., electrical cues) plays a particularly important role. Along with the development of tissue engineering and regenerative medicine (TERM), the positive effects of bioelectricity on the regeneration of excitable tissues have been well recognized through promoting cell proliferation, differentiation and migration and tissue functionalities. Conductive biomaterials have emerged as enabling tools to improve the outcomes of excitable tissue regeneration by facilitating the transmission of endogenous bioelectricity or electrical stimulation to electrically-isolated cells and tissues. Moreover, advanced electrical functionalities of conductive biomaterials can realize more controllable and smart TERM approaches. In this review, conductive biomaterials employed for TERM applications are comprehensively reviewed. First, the biological basis underlying the function of conductive biomaterials is introduced. Second, rational design strategies for conductive biomaterials displaying favorable microenvironmental cues (e.g., electrical, mechanical, structural) and electrical functionalities are summarized from the aspects of conductive and nonconductive components, biomaterial formats, spatial distribution of components, and anisotropy. Subsequently, strategies for the application of conductive biomaterials in TERM of excitable tissues, including nerves, myocardium, skeleton muscles, bones and skin/wounds, are reviewed. Finally, the future perspectives of conductive biomaterials for TERM applications are given.