{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:50:35Z","timestamp":1790380235858,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52171244"],"award-info":[{"award-number":["52171244"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>\n                    Osteonecrosis of the femoral head (ONFH) is a common condition that greatly affects patients\u2019 quality of life, yet current treatments often have limited effectiveness. This study aimed to explore how a porous titanium alloy scaffold coated with barium titanate (BaTiO\n                    <jats:sub>3<\/jats:sub>\n                    ) could promote bone regeneration in ONFH. We employed various research methods including cell culture, piezoelectric property measurements, tissue-engineered scaffold fabrication, and\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    biocompatibility assessments. Our results showed that macrophages had better attachment and growth on the BaTiO\n                    <jats:sub>3<\/jats:sub>\n                    -coated porous titanium alloy (PTB) scaffold than on the uncoated porous titanium alloy (PT) scaffold, with no significant differences in apoptosis rates between the two groups. Furthermore, the PTB scaffolds reduced the expression of bone resorption markers, such as Cathepsin K, TRAP, and RANK, under dynamic loading conditions. This finding indicates their potential to inhibit osteoclast differentiation. Moreover, the BaTiO\n                    <jats:sub>3<\/jats:sub>\n                    coating enhanced the mechanical properties and biocompatibility of the scaffolds, evidenced by significantly higher alkaline phosphatase activity and calcium nodule formation in MC3T3-E1 osteoblasts cultured on PTB scaffolds. These findings underscore the dual role of BaTiO\n                    <jats:sub>3<\/jats:sub>\n                    in facilitating cellular responses and modulating signaling pathways involved in bone metabolism. Our study highlights the promise of BaTiO\n                    <jats:sub>3<\/jats:sub>\n                    -coated titanium alloy scaffolds as an innovative approach to enhance bone regeneration in ONFH, paving the way for future clinical applications and the development of advanced biomaterials for bone healing.\n                  <\/jats:p>","DOI":"10.3389\/fbioe.2025.1671695","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T05:44:52Z","timestamp":1757655892000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The effect of barium titanate-coated titanium alloy scaffolds on bone regeneration in osteonecrosis of the femoral head models: a comprehensive analysis based on in vitro and in vivo experiments"],"prefix":"10.3389","volume":"13","author":[{"given":"Yu","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangfei","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxing","family":"Xian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1002\/jbm.a.34879","article-title":"Biocompatible evaluation of barium titanate foamed ceramic structures for orthopedic applications","volume":"102","author":"Ball","year":"2014","journal-title":"J. Biomed. Mater Res. a"},{"key":"B2","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s00402-010-1218-9","article-title":"Frictional and bone ingrowth properties of engineered surface topographies produced by electron beam technology","volume":"131","author":"Biemond","year":"2011","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"B3","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.abb.2008.03.018","article-title":"Functions of rankl\/rank\/opg in bone modeling and remodeling","volume":"473","author":"Boyce","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4073","DOI":"10.1016\/j.bioactmat.2021.04.016","article-title":"Improved activity of mc3t3-e1 cells by the exciting piezoelectric batio3\/tc4 using low-intensity pulsed ultrasound","volume":"6","author":"Cai","year":"2021","journal-title":"Bioact. Mater."},{"key":"B5","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1080\/03008200600858783","article-title":"Pulsed electromagnetic fields accelerate apoptotic rate in osteoclasts","volume":"47","author":"Chang","year":"2006","journal-title":"Connect. Tissue Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/s002560050277","article-title":"Avascular osteonecrosis of the acetabulum","volume":"26","author":"Fink","year":"1997","journal-title":"Skelet. Radiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"045006","DOI":"10.1088\/1748-6041\/7\/4\/045006","article-title":"Osteogenic differentiation of mc3t3-e1 cells on different titanium surfaces","volume":"7","author":"Hakki","year":"2012","journal-title":"Biomed. Mater"},{"key":"B8","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s11420-009-9107-x","article-title":"Sas weekly rounds: avascular necrosis","volume":"5","author":"Hamilton","year":"2009","journal-title":"HSS J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"113339","DOI":"10.1016\/j.colsurfb.2023.113339","article-title":"Surface modification techniques of titanium and titanium alloys for biomedical orthopaedics applications: a review","volume":"227","author":"Han","year":"2023","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"B10","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1002\/ame2.12300","article-title":"The bioelectrical properties of bone tissue","volume":"6","author":"Heng","year":"2023","journal-title":"Animal Models Exp. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3390\/jfb14010018","article-title":"Strategies of macrophages to maintain bone homeostasis and promote bone repair: a narrative review","volume":"14","author":"Hu","year":"2022","journal-title":"J. Funct. Biomater."},{"key":"B12","doi-asserted-by":"publisher","first-page":"120280","DOI":"10.1016\/j.biomaterials.2020.120280","article-title":"Electrical stimulation and piezoelectric biomaterials for bone tissue engineering applications","volume":"258","author":"Khare","year":"2020","journal-title":"Biomaterials"},{"key":"B13","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.jallcom.2010.01.026","article-title":"Effects of structural property and surface modification of ti6ta4sn scaffolds on the response of saos2 cells for bone tissue engineering","volume":"494","author":"Li","year":"2010","journal-title":"J. Alloy Compd."},{"key":"B14","doi-asserted-by":"publisher","first-page":"51885","DOI":"10.1021\/acsami.0c10957","article-title":"Biological effects of a three-dimensionally printed ti6al4v scaffold coated with piezoelectric batio3 nanoparticles on bone formation","volume":"12","author":"Liu","year":"2020","journal-title":"Acs Appl. Mater Inter"},{"key":"B15","doi-asserted-by":"publisher","first-page":"321","DOI":"10.3892\/etm.2022.11250","article-title":"Treatment of non-traumatic avascular necrosis of the femoral head (review)","volume":"23","author":"Liu","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"44111","DOI":"10.1021\/acsami.2c11131","article-title":"Enhanced cell osteogenesis and osteoimmunology regulated by piezoelectric biomaterials with controllable surface potential and charges","volume":"14","author":"Mao","year":"2022","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B17","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.lfs.2018.03.038","article-title":"Continuous application of compressive force induces fusion of osteoclast-like raw264.7 cells via upregulation of rank and downregulation of lgr4","volume":"201","author":"Matsuike","year":"2018","journal-title":"Life Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"17253","DOI":"10.1073\/pnas.1308887110","article-title":"Modulation of macrophage phenotype by cell shape","volume":"110","author":"McWhorter","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1136\/annrheumdis-2015-207593","article-title":"Netrin-1 is highly expressed and required in inflammatory infiltrates in wear particle-induced osteolysis","volume":"75","author":"Mediero","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"200","DOI":"10.3390\/bioengineering8120200","article-title":"Tissue engineering strategies for treating avascular necrosis of the femoral head","volume":"8","author":"Murab","year":"2021","journal-title":"Bioeng. (Basel)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1302\/2058-5241.4.180036","article-title":"Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment","volume":"4","author":"Petek","year":"2019","journal-title":"EFORT Open Rev."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.actbio.2018.11.018","article-title":"Osseointegration and current interpretations of the bone-implant interface","volume":"84","author":"Shah","year":"2019","journal-title":"Acta Biomater."},{"key":"B23","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.jmbbm.2017.06.024","article-title":"The fabrication and characterization of barium titanate\/akermanite nano-bio-ceramic with a suitable piezoelectric coefficient for bone defect recovery","volume":"74","author":"Shokrollahi","year":"2017","journal-title":"J. Mech. Behav. Biomed. Mater"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e2206401","DOI":"10.1002\/smll.202206401","article-title":"A comprehensive review on barium titanate nanoparticles as a persuasive piezoelectric material for biomedical applications: prospects and challenges","volume":"19","author":"Sood","year":"2023","journal-title":"Small"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3421","DOI":"10.1002\/bit.27142","article-title":"Direct electrical stimulation enhances osteogenesis by inducing bmp2 and spp1 expressions from macrophages and preosteoblasts","volume":"116","author":"Srirussamee","year":"2019","journal-title":"Biotechnol. Bioeng."},{"key":"B26","doi-asserted-by":"publisher","first-page":"114979","DOI":"10.1016\/j.addr.2023.114979","article-title":"Biomaterial-assisted macrophage cell therapy for regenerative medicine","volume":"199","author":"Sung","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.actbio.2018.04.026","article-title":"Piezoelectric materials as stimulatory biomedical materials and scaffolds for bone repair","volume":"73","author":"Tandon","year":"2018","journal-title":"Acta Biomater."},{"key":"B28","doi-asserted-by":"publisher","first-page":"43360","DOI":"10.1038\/srep43360","article-title":"Fabrication and in vitro biological properties of piezoelectric bioceramics for bone regeneration","volume":"7","author":"Tang","year":"2017","journal-title":"Sci. Rep-Uk"},{"key":"B29","doi-asserted-by":"publisher","first-page":"156","DOI":"10.7150\/ijbs.18334","article-title":"Analysis of early stage osteonecrosis of the human femoral head and the mechanism of femoral head collapse","volume":"14","author":"Wang","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"103738","DOI":"10.1016\/j.jmbbm.2020.103738","article-title":"A 3d printed porous titanium alloy rod with biogenic lamellar configuration for treatment of the early-stage femoral head osteonecrosis in sheep","volume":"106","author":"Wang","year":"","journal-title":"J. Mech. Behav. Biomed. Mater"},{"key":"B31","doi-asserted-by":"publisher","first-page":"28684","DOI":"10.1021\/acsomega.0c03824","article-title":"Effect of pore size on the physicochemical properties and osteogenesis of ti6al4v porous scaffolds with bionic structure","volume":"5","author":"Wang","year":"","journal-title":"ACS Omega"},{"key":"B32","doi-asserted-by":"publisher","first-page":"112499","DOI":"10.1016\/j.msec.2021.112499","article-title":"Large-pore-size ti6al4v scaffolds with different pore structures for vascularized bone regeneration","volume":"131","author":"Wang","year":"2021","journal-title":"Mater Sci. Eng. C Mater Biol. Appl."},{"key":"B33","doi-asserted-by":"publisher","first-page":"11305","DOI":"10.1021\/acs.chemrev.0c00895","article-title":"Immunomodulatory biomaterials for tissue repair","volume":"121","author":"Whitaker","year":"2021","journal-title":"Chem. Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"17550","DOI":"10.1016\/j.ceramint.2021.03.073","article-title":"Novel dam-like effect based on piezoelectric energy conversion for drug sustained release of drug-loaded tio2 @ batio3 coaxial nanotube coating","volume":"47","author":"Wu","year":"2021","journal-title":"Ceram. Int."},{"key":"B35","doi-asserted-by":"publisher","first-page":"121990","DOI":"10.1016\/j.biomaterials.2022.121990","article-title":"Electrical stimulation of piezoelectric batio3 coated ti6al4v scaffolds promotes anti-inflammatory polarization of macrophages and bone repair via mapk\/jnk inhibition and oxphos activation","volume":"293","author":"Wu","year":"2023","journal-title":"Biomaterials"},{"key":"B36","doi-asserted-by":"publisher","first-page":"44356","DOI":"10.1021\/acsami.7b16206","article-title":"Novel reduced graphene oxide\/zinc silicate\/calcium silicate electroconductive biocomposite for stimulating osteoporotic bone regeneration","volume":"9","author":"Xiong","year":"2017","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B37","doi-asserted-by":"publisher","first-page":"664871","DOI":"10.3389\/fimmu.2021.664871","article-title":"The macrophage-osteoclast axis in osteoimmunity and osteo-related diseases","volume":"12","author":"Yao","year":"2021","journal-title":"Front. Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2754","DOI":"10.3390\/polym12112754","article-title":"Progress in the applications of smart piezoelectric materials for medical devices","volume":"12","author":"Zaszczy\u0144ska","year":"2020","journal-title":"Polymers-Basel"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.4103\/0366-6999.168017","article-title":"Prevalence of nontraumatic osteonecrosis of the femoral head and its associated risk factors in the chinese population: results from a nationally representative survey","volume":"128","author":"Zhao","year":"2015","journal-title":"Chin. Med. J. Engl."},{"key":"B40","doi-asserted-by":"publisher","first-page":"10221","DOI":"10.1039\/d0tb01601b","article-title":"Mimicking the electrophysiological microenvironment of bone tissue using electroactive materials to promote its regeneration","volume":"8","author":"Zheng","year":"2020","journal-title":"J. Mater Chem. B"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e2302702","DOI":"10.1002\/advs.202302702","article-title":"Evolution from bioinert to bioresorbable: in vivo comparative study of additively manufactured metal bone scaffolds","volume":"10","author":"Zhou","year":"2023","journal-title":"Adv. Sci. (Weinh)"}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2025.1671695\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T05:44:53Z","timestamp":1757655893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2025.1671695\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":41,"alternative-id":["10.3389\/fbioe.2025.1671695"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2025.1671695","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]},"article-number":"1671695"}}