Piezoelectric scaffolds for bone regeneration: a systematic review of preclinical studies

Critical-sized bone defects remain a major challenge and often require reconstruction grafts. Conventional scaffolds don't reproduce the dynamic electromechanical behavior of native bone. Piezoelectric scaffolds have emerged as a promising strategy to overcome these limitations by converting mechanical stimuli into bioactive electrical signals capable of enhancing osteogenesis.

A systematic review was conducted in accordance with the PRISMA 2020 guidelines and registered in PROSPERO (ID: 1359740). A comprehensive search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Central Register of Controlled Trials was performed. In vivo animal and clinical studies evaluating piezoelectric scaffolds for bone defect repair were included. Data extraction and risk of bias assessment were performed independently by two reviewers. Outcomes of interest included micro-computed tomography (micro-CT), histological findings, and biomechanical properties.

Ten preclinical in vivo studies (2020-2025) were included. No eligible human clinical studies were identified. The included studies involved mainly rodent models, with some studies in rabbits and sheep. Most studies investigated critical-sized calvarial defects, while others evaluated load-bearing models. Piezoelectric scaffolds-primarily based on PVDF, PVDF-TrFE, and BaTiO₃ composites-consistently demonstrated improved bone regeneration compared with conventional scaffolds. Micro-CT analysis showed higher bone volume fraction (BV/TV) and bone mineral density (BMD) across studies, with BV/TV values reaching approximately 35%-36% at 8 weeks in several models. Histological analyses confirmed enhanced new bone formation, improved tissue organization, and better scaffold-bone integration, often with reduced fibrous tissue formation. Additive manufacturing techniques enabled precise control of scaffold architecture and were widely used, while external mechanical stimulation further enhanced osteogenic outcomes in some studies.

Piezoelectric scaffolds represent a promising approach for bone regeneration, demonstrating superior regenerative performance compared with conventional scaffolds in preclinical models. Their ability to generate bioactive electrical signals, combined with advanced fabrication techniques, supports their potential for clinical translation. However, current evidence is limited to preclinical studies with heterogeneous methodologies. Further standardized studies and clinical investigations are needed to confirm their safety, efficacy, and long-term performance.