Abstract
This Perspective explores the transformative potential of piezoelectric biomaterials in addressing one of the most persistent challenges in craniomaxillofacial (CMF) bone regeneration: the reliable healing of large, irregular, and functionally demanding skeletal defects. Traditional approaches─autologous grafts, allografts, and inert synthetic scaffolds─are limited by donor-site morbidity, immunogenicity, mechanical insufficiency, and inadequate bioactivity. In contrast, piezoelectric materials offer a dynamic alternative, generating endogenous-like electrical cues in response to mechanical stress, thereby mimicking the body's natural bone homeostasis and healing mechanisms. Bone's intrinsic piezoelectricity plays a critical role in cellular behavior through electromechanical signaling. Inspired by this, exogenous piezoelectric scaffolds─composed of polymers (e.g., PVDF, PLA), ceramics (e.g., BaTiO3, HA), or their composites─have been engineered to convert physiological strain into localized electric potentials that activate osteogenic pathways and modulate immune responses. In vitro and in vivo studies consistently demonstrate enhanced osteoblast proliferation, differentiation, mineralization, and macrophage polarization toward pro-healing phenotypes. Notably, BaTiO3/PLA membranes, magnetically or mechanically activated composites, and 3D-printed piezoelectric scaffolds have shown accelerated bone formation and vascularization in preclinical CMF defect models. Beyond bone repair, these materials exhibit antimicrobial and immunomodulatory properties, making them uniquely suited for complex, load-bearing, and inflamed environments such as mandible or periodontal defects. The convergence of advanced fabrication techniques (e.g., electrospinning, 3D/4D printing) and smart materials design now enables patient-specific, bioactive implants capable of real-time mechanotransduction. While no human trials have yet been reported, the clinical trajectory is supported by existing FDA-approved piezoelectric devices and growing preclinical validation. Future progress hinges on overcoming translational barriers, including regulatory clearance, scalable manufacturing, and mechanical reliability under functional loads. Ultimately, piezoelectric biomaterials represent a next-generation paradigm for CMF regeneration, combining mechanical support, immunomodulation, and bioelectric stimulation to enable personalized and robust bone regeneration.