Noninvasive manipulation of cell adhesion for cell harvesting with piezoelectric composite film

Abstract Cell sheet harvesting has recently emerged as a promising strategy for scaffold-free cell transplantation and tissue engineering. It is critical to achieve the disconnection between cell and its adherent support while maintaining the availability of cell sheet. Hence, the regulation of cell adhesion behavior often becomes the primary consideration for designing biomaterials used for cell sheet harvesting. The stimuli-responsive biomaterials can rationally modulate cell behaviors, especially adhesion performance. However, modulation of cell adhesion through noninvasive and highly efficient method is still greatly needed. Herein, a noninvasive low-intensity ultrasound-mediated cell harvesting is demonstrated based on the piezoelectric effect of polyvinylidene fluoride (PVDF)/barium titanate (BaTiO3, BTO) composite film with superior electromechanical conversion ability. We found that the piezoelectric effect triggered by ultrasound (US) can modulate the absorption and secondary structure of adhesive protein fibronectin (FN) on the composite film, which further influenced cell adhesion force to finally obtain free-standing cell sheets. The detached cell sheets with accurate comtrol retained their viability and excellent proliferative capability. These findings highlight the ability of the piezoelectric biomaterials for cell sheet engineering to serve as a noninvasive and accurately controllable platform via regulating surface protein adsorption and conformation, which indicates great application prospect of this piezoelectricity-based cell harvesting method in regenerative medicine.