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Orthopedic implants can aid in healing injuries to an extent that exceeds the natural regenerative capabilities of bone to repair fractures or large bone defects. Autografts and allografts are the standard implants used, but disadvantages such as donor site complications, a limited quantity of transplantable bone, and high costs have led to an increased demand for synthetic bone graft substitutes. However, replicating the complex physiological properties of biological bone, much less recapitulating its complex tissue functions, is challenging. Extensive efforts to design biocompatible implants that mimic the natural healing processes in bone have led to the investigation of piezoelectric smart materials because the bone has natural piezoelectric properties. Piezoelectric materials facilitate bone regeneration either by accumulating electric charge in response to mechanical stress, which mimics bioelectric signals through the direct piezoelectric effect or by providing mechanical stimulation in response to electrical stimulation through the converse piezoelectric effect. Although both effects are beneficial, the converse piezoelectric effect can address bone atrophy from stress shielding and immobility by improving the mechanical response of a healing defect. Mechanical stimulation has a positive impact on bone regeneration by activating cellular pathways that increase bone formation and decrease bone resorption. This review will highlight the potential of the converse piezoelectric effect to enhance bone regeneration by discussing the activation of beneficial cellular pathways, the properties of piezoelectric biomaterials, and the potential for the more effective administration of the converse piezoelectric effect using wireless control.<\/jats:p>","DOI":"10.1089\/bioe.2021.0019","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T11:43:38Z","timestamp":1632483818000},"page":"255-271","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":117,"title":["Enhancement of Bone Regeneration Through the Converse Piezoelectric Effect, A Novel Approach for Applying Mechanical Stimulation"],"prefix":"10.1177","volume":"3","author":[{"given":"Amber","family":"Carter","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA."},{"name":"Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Popowski","sequence":"additional","affiliation":[{"name":"Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA."},{"name":"Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Cheng","sequence":"additional","affiliation":[{"name":"Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA."},{"name":"Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina, USA."},{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA."},{"name":"Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alon","family":"Greenbaum","sequence":"additional","affiliation":[{"name":"Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA."},{"name":"Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances S.","family":"Ligler","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6946-5370","authenticated-orcid":false,"given":"Adele","family":"Moatti","sequence":"additional","affiliation":[{"name":"Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA."},{"name":"Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2011.06.011"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-9-66"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2017.05.007"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-018-0059-8"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0032-9"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201909045"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2015.08.043"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1143\/JPSJ.12.1158"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.04.026"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199201000-00014"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/ma11010014"},{"key":"e_1_3_4_13_2","first-page":"975","article-title":"Chemical and Biochemical Basis of Bone Cell","volume":"3","author":"Feng X","year":"2010","unstructured":"Feng X. 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