{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:01:26Z","timestamp":1793228486973,"version":"4.5.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Critical-sized bone defects remain a major challenge and often require reconstruction grafts. Conventional scaffolds don\u2019t 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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.\n                      <jats:italic>In vivo<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ten preclinical\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies (2020\u20132025) 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\u2014primarily based on PVDF, PVDF-TrFE, and BaTiO\n                      <jats:sub>3<\/jats:sub>\n                      composites\u2014consistently 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%\u201336% at 8 weeks in several models. Histological analyses confirmed enhanced new bone formation, improved tissue organization, and better scaffold\u2013bone 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2026.1848820","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:38:00Z","timestamp":1782797880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Piezoelectric scaffolds for bone regeneration: a systematic review of preclinical studies"],"prefix":"10.3389","volume":"14","author":[{"given":"Marco","family":"Minelli","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Rozzano, Italy"]},{"name":"IRCCS Humanitas Research Hospital","place":["Rozzano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Micalizzi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Rozzano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Longobardi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Rozzano, Italy"]},{"name":"IRCCS Humanitas Research Hospital","place":["Rozzano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta","family":"Kon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Rozzano, Italy"]},{"name":"IRCCS Humanitas Research Hospital","place":["Rozzano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Oliva","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Rozzano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Della Rocca","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital","place":["Rozzano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"386","DOI":"10.3390\/mi16040386","article-title":"A comprehensive review of piezoelectric PVDF polymer fabrications and characteristics","volume":"16","author":"Ahbab","year":"2025","journal-title":"Micromachines (Basel)."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6886","DOI":"10.1039\/d4tb00785a","article-title":"Design and development of 3D printed shape memory triphasic polymer-ceramic bioactive scaffolds for bone tissue engineering","volume":"12","author":"Ansari","year":"2024","journal-title":"J. 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