{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:51:34Z","timestamp":1790952694204,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81960914"],"award-info":[{"award-number":["81960914"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shaanxi Provincial Health and Medical Research and Innovation Capacity Improvement Plan Project","award":["2024TD-19"],"award-info":[{"award-number":["2024TD-19"]}]},{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2023-JC-QN-0997"],"award-info":[{"award-number":["2023-JC-QN-0997"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shaanxi Provincial Laboratory Key Project","award":["2025SYS-SYSZD-089"],"award-info":[{"award-number":["2025SYS-SYSZD-089"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Oral Health"],"DOI":"10.1186\/s12903-025-06495-0","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T07:07:59Z","timestamp":1753168079000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Three-dimensional scaffold-free periodontal ligament stem cell pellets for alveolar ridge preservation: an in vitro and in vivo study"],"prefix":"10.1186","volume":"25","author":[{"given":"Xiang","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siya","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6906-8279","authenticated-orcid":false,"given":"Sadam Ahmed","family":"Elayah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Ahmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2248-4451","authenticated-orcid":false,"given":"Sijia","family":"Na","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"6495_CR1","doi-asserted-by":"crossref","unstructured":"Stamnitz S, Klimczak A. Mesenchymal stem cells, bioactive factors, and scaffolds in bone repair: from research perspectives to clinical practice. Cells 2021;10(8).","DOI":"10.3390\/cells10081925"},{"issue":"6","key":"6495_CR2","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1055\/s-0035-1570749","volume":"6","author":"A Tuchman","year":"2016","unstructured":"Tuchman A, Brodke DS, Youssef JA, Meisel HJ, Dettori JR, Park JB, Yoon ST, Wang JC. Iliac crest bone graft versus local autograft or allograft for lumbar spinal fusion: A systematic review. Global Spine J. 2016;6(6):592\u2013606.","journal-title":"Global Spine J"},{"key":"6495_CR3","doi-asserted-by":"publisher","first-page":"112466","DOI":"10.1016\/j.msec.2021.112466","volume":"130","author":"CE Gillman","year":"2021","unstructured":"Gillman CE, Jayasuriya AC. FDA-approved bone grafts and bone graft substitute devices in bone regeneration. Mater Sci Eng C Mater Biol Appl. 2021;130:112466.","journal-title":"Mater Sci Eng C Mater Biol Appl"},{"issue":"12","key":"6495_CR4","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1111\/clr.13528","volume":"30","author":"FR Grassi","year":"2019","unstructured":"Grassi FR, Grassi R, Rapone B, Alemanno G, Balena A, Kalemaj Z. Dimensional changes of buccal bone plate in immediate implants inserted through open flap, open flap and bone grafting and flapless techniques: A cone-beam computed tomography randomized controlled clinical trial. Clin Oral Implants Res. 2019;30(12):1155\u201364.","journal-title":"Clin Oral Implants Res"},{"issue":"1","key":"6495_CR5","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/1749-799X-9-18","volume":"9","author":"A Oryan","year":"2014","unstructured":"Oryan A, Alidadi S, Moshiri A, Maffulli N. Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res. 2014;9(1):18.","journal-title":"J Orthop Surg Res"},{"key":"6495_CR6","doi-asserted-by":"crossref","unstructured":"Alghuwainem A, Alshareeda AT, Alsowayan B. Scaffold-Free 3-D cell sheet technique bridges the gap between 2-D cell culture and animal models. Int J Mol Sci 2019;20(19).","DOI":"10.3390\/ijms20194926"},{"issue":"3","key":"6495_CR7","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s10529-019-02649-7","volume":"41","author":"M Chen","year":"2019","unstructured":"Chen M, Xu Y, Zhang T, Ma Y, Liu J, Yuan B, Chen X, Zhou P, Zhao X, Pang F, et al. Mesenchymal stem cell sheets: a new cell-based strategy for bone repair and regeneration. Biotechnol Lett. 2019;41(3):305\u201318.","journal-title":"Biotechnol Lett"},{"issue":"1","key":"6495_CR8","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1186\/s13287-018-1064-1","volume":"9","author":"D Wu","year":"2018","unstructured":"Wu D, Wang Z, Wang J, Geng Y, Zhang Z, Li Y, Li Q, Zheng Z, Cao Y, Zhang ZY. Development of a micro-tissue-mediated injectable bone tissue engineering strategy for large segmental bone defect treatment. Stem Cell Res Ther. 2018;9(1):331.","journal-title":"Stem Cell Res Ther"},{"issue":"1","key":"6495_CR9","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1186\/s13287-021-02456-w","volume":"12","author":"J Fu","year":"2021","unstructured":"Fu J, Wang Y, Jiang Y, Du J, Xu J, Liu Y. Systemic therapy of MSCs in bone regeneration: a systematic review and meta-analysis. Stem Cell Res Ther. 2021;12(1):377.","journal-title":"Stem Cell Res Ther"},{"issue":"3","key":"6495_CR10","doi-asserted-by":"publisher","first-page":"e12997","DOI":"10.1111\/cpr.12997","volume":"54","author":"Q Liang","year":"2021","unstructured":"Liang Q, Du L, Zhang R, Kang W, Ge S. Stromal cell-derived factor-1\/Exendin-4 cotherapy facilitates the proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells in vitro and promotes periodontal bone regeneration in vivo. Cell Prolif. 2021;54(3):e12997.","journal-title":"Cell Prolif"},{"key":"6495_CR11","doi-asserted-by":"publisher","first-page":"204173142110414","DOI":"10.1177\/20417314211041428","volume":"12","author":"F Batool","year":"2021","unstructured":"Batool F, \u00d6z\u00e7elik H, Stutz C, Gegout PY, Benkirane-Jessel N, Petit C, Huck O. Modulation of immune-inflammatory responses through surface modifications of biomaterials to promote bone healing and regeneration. J Tissue Eng. 2021;12:20417314211041428.","journal-title":"J Tissue Eng"},{"issue":"6","key":"6495_CR12","doi-asserted-by":"publisher","first-page":"749","DOI":"10.3892\/br.2015.522","volume":"3","author":"G Chen","year":"2015","unstructured":"Chen G, Qi Y, Niu L, Di T, Zhong J, Fang T, Yan W. Application of the cell sheet technique in tissue engineering. Biomed Rep. 2015;3(6):749\u201357.","journal-title":"Biomed Rep"},{"issue":"21","key":"6495_CR13","doi-asserted-by":"publisher","first-page":"e1800457","DOI":"10.1002\/adhm.201800457","volume":"7","author":"C Vaquette","year":"2018","unstructured":"Vaquette C, Pilipchuk SP, Bartold PM, Hutmacher DW, Giannobile WV, Ivanovski S. Tissue engineered constructs for periodontal regeneration: current status and future perspectives. Adv Healthc Mater. 2018;7(21):e1800457.","journal-title":"Adv Healthc Mater"},{"issue":"3","key":"6495_CR14","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1002\/term.1686","volume":"10","author":"S Na","year":"2016","unstructured":"Na S, Zhang H, Huang F, Wang W, Ding Y, Li D, Jin Y. Regeneration of dental pulp\/dentine complex with a three-dimensional and scaffold-free stem-cell sheet-derived pellet. J Tissue Eng Regen Med. 2016;10(3):261\u201370.","journal-title":"J Tissue Eng Regen Med"},{"issue":"22","key":"6495_CR15","doi-asserted-by":"publisher","first-page":"5560","DOI":"10.1016\/j.biomaterials.2012.04.038","volume":"33","author":"C Vaquette","year":"2012","unstructured":"Vaquette C, Fan W, Xiao Y, Hamlet S, Hutmacher DW, Ivanovski S. A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone\/periodontal ligament complex. Biomaterials. 2012;33(22):5560\u201373.","journal-title":"Biomaterials"},{"key":"6495_CR16","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/978-1-4939-6685-1_23","volume":"1537","author":"A Farag","year":"2017","unstructured":"Farag A, Vaquette C, Hutmacher DW, Bartold PM, Ivanovski S. Fabrication and characterization of decellularized periodontal ligament cell sheet constructs. Methods Mol Biol. 2017;1537:403\u201312.","journal-title":"Methods Mol Biol"},{"key":"6495_CR17","doi-asserted-by":"crossref","unstructured":"Walma DAC, Yamada KM. The extracellular matrix in development. Development 2020;147(10).","DOI":"10.1242\/dev.175596"},{"issue":"4","key":"6495_CR18","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.tibtech.2019.11.005","volume":"38","author":"S Bose","year":"2020","unstructured":"Bose S, Sarkar N. Natural medicinal compounds in bone tissue engineering. Trends Biotechnol. 2020;38(4):404\u201317.","journal-title":"Trends Biotechnol"},{"issue":"9","key":"6495_CR19","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.3727\/096368912X661319","volume":"23","author":"X Liu","year":"2014","unstructured":"Liu X, Wu M, Peng Y, Chen X, Sun J, Huang F, Fan Z, Zhou H, Wu X, Yu G, et al. Improvement in poor graft function after allogeneic hematopoietic stem cell transplantation upon administration of mesenchymal stem cells from third-party donors: a pilot prospective study. Cell Transpl. 2014;23(9):1087\u201398.","journal-title":"Cell Transpl"},{"issue":"6","key":"6495_CR20","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1902\/jop.2011.110267","volume":"83","author":"H Xie","year":"2012","unstructured":"Xie H, Liu H. A novel mixed-type stem cell pellet for cementum\/periodontal ligament-like complex. J Periodontol. 2012;83(6):805\u201315.","journal-title":"J Periodontol"},{"key":"6495_CR21","doi-asserted-by":"crossref","unstructured":"Silver FH, Kelkar N, Deshmukh T. Molecular Basis for Mechanical Properties of ECMs: Proposed Role of Fibrillar Collagen and Proteoglycans in Tissue Biomechanics. Biomolecules 2021;11(7).","DOI":"10.3390\/biom11071018"},{"issue":"7822","key":"6495_CR22","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/s41586-020-2612-2","volume":"584","author":"O Chaudhuri","year":"2020","unstructured":"Chaudhuri O, Cooper-White J, Janmey PA, Mooney DJ, Shenoy VB. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature. 2020;584(7822):535\u201346.","journal-title":"Nature"},{"issue":"42","key":"6495_CR23","doi-asserted-by":"publisher","first-page":"25999","DOI":"10.1073\/pnas.2008801117","volume":"117","author":"JM Grolman","year":"2020","unstructured":"Grolman JM, Weinand P, Mooney DJ. Extracellular matrix plasticity as a driver of cell spreading. Proc Natl Acad Sci U S A. 2020;117(42):25999\u20136007.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"6495_CR24","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.trsl.2013.11.003","volume":"163","author":"BN Brown","year":"2014","unstructured":"Brown BN, Badylak SF. Extracellular matrix as an inductive scaffold for functional tissue reconstruction. Transl Res. 2014;163(4):268\u201385.","journal-title":"Transl Res"},{"issue":"4","key":"6495_CR25","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.addr.2012.03.009","volume":"65","author":"RA P\u00e9rez","year":"2013","unstructured":"P\u00e9rez RA, Won JE, Knowles JC, Kim HW. Naturally and synthetic smart composite biomaterials for tissue regeneration. Adv Drug Deliv Rev. 2013;65(4):471\u201396.","journal-title":"Adv Drug Deliv Rev"},{"issue":"21","key":"6495_CR26","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1039\/c3tb00043e","volume":"1","author":"JH Lee","year":"2013","unstructured":"Lee JH, Park JH, Yun YR, Jang JH, Lee EJ, Chrzanowski W, Wall IB, Kim HW. Tethering bi-functional protein onto mineralized polymer scaffolds to regulate mesenchymal stem cell behaviors for bone regeneration. J Mater Chem B. 2013;1(21):2731\u201341.","journal-title":"J Mater Chem B"},{"issue":"3","key":"6495_CR27","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1002\/jcb.10031","volume":"84","author":"RS Carvalho","year":"2002","unstructured":"Carvalho RS, Bumann A, Schaffer JL, Gerstenfeld LC. Predominant integrin ligands expressed by osteoblasts show Preferential regulation in response to both cell adhesion and mechanical perturbation. J Cell Biochem. 2002;84(3):497\u2013508.","journal-title":"J Cell Biochem"},{"issue":"3","key":"6495_CR28","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.bone.2007.04.191","volume":"41","author":"JA Gordon","year":"2007","unstructured":"Gordon JA, Tye CE, Sampaio AV, Underhill TM, Hunter GK, Goldberg HA. Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization in vitro. Bone. 2007;41(3):462\u201373.","journal-title":"Bone"},{"key":"6495_CR29","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.biomaterials.2016.02.003","volume":"86","author":"JM Aamodt","year":"2016","unstructured":"Aamodt JM, Grainger DW. Extracellular matrix-based biomaterial scaffolds and the host response. Biomaterials. 2016;86:68\u201382.","journal-title":"Biomaterials"},{"key":"6495_CR30","doi-asserted-by":"publisher","first-page":"e919159","DOI":"10.12659\/MSM.919159","volume":"26","author":"J Si","year":"2020","unstructured":"Si J, Wang C, Zhang D, Wang B, Zhou Y. Osteopontin in bone metabolism and bone diseases. Med Sci Monit. 2020;26:e919159.","journal-title":"Med Sci Monit"},{"issue":"12","key":"6495_CR31","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1359\/jbmr.1999.14.12.2015","volume":"14","author":"KN Fedde","year":"1999","unstructured":"Fedde KN, Blair L, Silverstein J, Coburn SP, Ryan LM, Weinstein RS, Waymire K, Narisawa S, Mill\u00e1n JL, MacGregor GR, et al. Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. J Bone Min Res. 1999;14(12):2015\u201326.","journal-title":"J Bone Min Res"},{"issue":"4","key":"6495_CR32","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s00418-018-1640-6","volume":"149","author":"T Komori","year":"2018","unstructured":"Komori T. Runx2, an inducer of osteoblast and chondrocyte differentiation. Histochem Cell Biol. 2018;149(4):313\u201323.","journal-title":"Histochem Cell Biol"},{"issue":"4","key":"6495_CR33","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1177\/0022034520905660","volume":"99","author":"G Avila-Ortiz","year":"2020","unstructured":"Avila-Ortiz G, Gubler M, Romero-Bustillos M, Nicholas CL, Zimmerman MB, Barwacz CA. Efficacy of alveolar ridge preservation: A randomized controlled trial. J Dent Res. 2020;99(4):402\u20139.","journal-title":"J Dent Res"},{"issue":"8","key":"6495_CR34","doi-asserted-by":"publisher","first-page":"4471","DOI":"10.1007\/s00784-023-05068-1","volume":"27","author":"I El-Sioufi","year":"2023","unstructured":"El-Sioufi I, Oikonomou I, Koletsi D, Bobetsis YA, Madianos PN, Vassilopoulos S. Clinical evaluation of different alveolar ridge preservation techniques after tooth extraction: a randomized clinical trial. Clin Oral Investig. 2023;27(8):4471\u201380.","journal-title":"Clin Oral Investig"},{"key":"6495_CR35","doi-asserted-by":"publisher","first-page":"1163696","DOI":"10.3389\/fendo.2023.1163696","volume":"14","author":"SA Elayah","year":"2023","unstructured":"Elayah SA, Younis H, Cui H, Liang X, Sakran KA, Alkadasi B, Al-Moraissi EA, Albadani M, Al-Okad W, Tu J, et al. Alveolar ridge preservation in post-extraction sockets using concentrated growth factors: a split-mouth, randomized, controlled clinical trial. Front Endocrinol (Lausanne). 2023;14:1163696.","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"6495_CR36","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/prd.12518","volume":"93","author":"N Donos","year":"2023","unstructured":"Donos N, Akcali A, Padhye N, Sculean A, Calciolari E. Bone regeneration in implant dentistry: which are the factors affecting the clinical outcome? Periodontol 2000. 2023;93(1):26\u201355.","journal-title":"Periodontol 2000"}],"container-title":["BMC Oral Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-025-06495-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12903-025-06495-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-025-06495-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T17:12:12Z","timestamp":1757265132000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcoralhealth.biomedcentral.com\/articles\/10.1186\/s12903-025-06495-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6495"],"URL":"https:\/\/doi.org\/10.1186\/s12903-025-06495-0","relation":{},"ISSN":["1472-6831"],"issn-type":[{"value":"1472-6831","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,21]]},"assertion":[{"value":"8 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The project titled \u201c3D scaffold-free periodontal ligament stem cell pellet technology for periodontal tissue regeneration\u201d was approved by the Ethics Committee of Xi\u2019an Jiaotong University (approval NO. 2022\u2009\u2212\u20091433). It has been conducted following the ARRIVE guidelines 2.0 and adheres to the principles outlined in the Declaration of Helsinki. Before the isolation and culture of periodontal ligament stem cells, written informed consent was obtained from the parents or legal guardians of patients aged 14. In contrast, informed consent was directly obtained from patients aged 18.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1227"}}