3D/4D printed bio-piezoelectric smart scaffolds for next-generation bone tissue engineering

摘要

Piezoelectricity in native bones has been well recognized as the key factor in bone regeneration.Thus,bio-piezoelectric materials have gained substantial attention in repairing damaged bone by mimicking the tissue’s electrical microenvironment(EM).However,traditional manufacturing strategies still encounter limitations in creating personalized bio-piezoelectric scaffolds,hindering their clinical applications.Three-dimensional(3D)/four-dimensional(4D)printing technology based on the principle of layer-by-layer forming and stacking of discrete materials has demonstrated outstanding advantages in fabricating bio-piezoelectric scaffolds in a more complex-shaped structure.Notably,4D printing functionality-shifting bio-piezoelectric scaffolds can provide a time-dependent programmable tissue EM in response to external stimuli for bone regeneration.In this review,we first summarize the physicochemical properties of commonly used bio-piezoelectric materials(including polymers,ceramics,and their composites)and representative biological findings for bone regeneration.Then,we discuss the latest research advances in the 3D printing of bio-piezoelectric scaffolds in terms of feedstock selection,printing process,induction strategies,and potential applications.Besides,some related challenges such as feedstock scalability,printing resolution,stress-to-polarization conversion efficiency,and non-invasive induction ability after implantation have been put forward.Finally,we highlight the potential of shape/property/functionality-shifting smart 4D bio-piezoelectric scaffolds in bone tissue engineering(BTE).Taken together,this review emphasizes the appealing utility of 3D/4D printed biological piezoelectric scaffolds as next-generation BTE implants.