3D/4D printed bio-piezoelectric smart scaffolds for next-generation bone tissue engineering
Annan Chen, Jin Su, Yinjin Li, Haibo Zhang, Yusheng Shi, Chunze Yan, Jian Lü
Abstract
Abstract 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.