Interplay of piezoelectricity and electrical stimulation in tissue engineering and regenerative medicine

Bioelectronic medicine, involving physiologically relevant biophysical stimulation and piezoelectric biomaterials is perceived to transform the field of regenerative bioelectronics. The combinatorial effect has shown remarkable potential in guiding cell behavior and promoting the development of functional tissue-engineered constructs. Smart piezoelectric biomaterials, capable of generating electric charges under mechanical stress or deformation, have emerged as key players in tissue engineering applications. This comprehensive review explores the interplay between electrical stimulation, piezoelectric biomaterials, and cell functionality in regeneration of neural, bone, cardiac, skin, and vascular tissues. The inherent electrical activity (biopiezoelectricity) empowers piezoelectric scaffolds to replicate natural processes in the extracellular matrix. The synergy between surface charge polarization or electric field stimulation and the functional properties of piezoelectric biomaterials have been critically analyzed. These analyses demonstrate how such synergistic effects can modulate in vitro cell functionality and in vivo tissue regeneration. Moreover, the integration of data science approaches has the potential to optimize the design of piezoelectric scaffolds for specific tissue engineering and regenerative medicine applications.