{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:11:43Z","timestamp":1790010703109,"version":"4.0.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2014,2,20]],"date-time":"2014-02-20T00:00:00Z","timestamp":1392854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"EVO","award":["9L100"],"award-info":[{"award-number":["9L100"]}]},{"name":"EVO","award":["9H080"],"award-info":[{"award-number":["9H080"]}]},{"name":"EVO","award":["9P049"],"award-info":[{"award-number":["9P049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although isolated reports of hard-tissue reconstruction in the cranio-maxillofacial skeleton exist, multipatient case series are lacking. This study aimed to review the experience with 13 consecutive cases of cranio-maxillofacial hard-tissue defects at four anatomically different sites, namely frontal sinus (3 cases), cranial bone (5 cases), mandible (3 cases), and nasal septum (2 cases). Autologous adipose tissue was harvested from the anterior abdominal wall, and adipose-derived stem cells were cultured, expanded, and then seeded onto resorbable scaffold materials for subsequent reimplantation into hard-tissue defects. The defects were reconstructed with either bioactive glass or \u03b2-tricalcium phosphate scaffolds seeded with adipose-derived stem cells (ASCs), and in some cases with the addition of recombinant human bone morphogenetic protein-2. Production and use of ASCs were done according to good manufacturing practice guidelines. Follow-up time ranged from 12 to 52 months. Successful integration of the construct to the surrounding skeleton was noted in 10 of the 13 cases. Two cranial defect cases in which nonrigid resorbable containment meshes were used sustained bone resorption to the point that they required the procedure to be redone. One septal perforation case failed outright at 1 year because of the postsurgical resumption of the patient's uncontrolled nasal picking habit.<\/jats:p>","DOI":"10.5966\/sctm.2013-0173","type":"journal-article","created":{"date-parts":[[2014,2,21]],"date-time":"2014-02-21T00:01:33Z","timestamp":1392940893000},"page":"530-540","source":"Crossref","is-referenced-by-count":186,"title":["Adipose Stem Cells Used to Reconstruct 13 Cases With Cranio-Maxillofacial Hard-Tissue Defects"],"prefix":"10.1093","volume":"3","author":[{"given":"George K.","family":"S\u00e1ndor","sequence":"first","affiliation":[{"name":"Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland"},{"name":"Department of Oral and Maxillofacial Surgery, University of Oulu, Oulu, Finland"},{"name":"Oulu University Hospital, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jura","family":"Numminen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery and Oral Diseases, Tampere University Hospital, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Wolff","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland"},{"name":"Department of Otolaryngology, Head and Neck Surgery and Oral Diseases, Tampere University Hospital, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomo","family":"Thesleff","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Rehabilitation, Tampere University Hospital, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimo","family":"Miettinen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery and Oral Diseases, Tampere University Hospital, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veikko J.","family":"Tuovinen","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Central Hospital of Central Finland Health Care District, Jyv\u00e4skyl\u00e4, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Mannerstr\u00f6m","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimmi","family":"Patrikoski","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riitta","family":"Sepp\u00e4nen","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland"},{"name":"Department of Otolaryngology, Head and Neck Surgery and Oral Diseases, Tampere University Hospital, Tampere, Finland"},{"name":"Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Miettinen","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Rautiainen","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland"},{"name":"Department of Otolaryngology, Head and Neck Surgery and Oral Diseases, Tampere University Hospital, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"\u00d6hman","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Rehabilitation, Tampere University Hospital, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,20]]},"reference":[{"key":"2021122709142254700_R1","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.joms.2012.07.004","article-title":"Mandibular resection and reconstruction in the management of extensive ameloblastoma","volume":"71","author":"Bianchi","year":"2013","journal-title":"J Oral Maxillofac Surg"},{"key":"2021122709142254700_R2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/00006534-198907000-00014","article-title":"Fibula free flap: A new method of mandible reconstruction","volume":"84","author":"Hidalgo","year":"1989","journal-title":"Plast Reconstr Surg"},{"key":"2021122709142254700_R3","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1067\/moe.2003.42","article-title":"Comparison of conventional surgery with motorized trephine in bone harvest from the anterior iliac crest","volume":"95","author":"S\u00e0ndor","year":"2003","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"key":"2021122709142254700_R4","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1097\/PRS.0b013e3182402d9a","article-title":"What is the price to pay for a free fibula flap? A systematic review of donor-site morbidity following free fibula flap surgery","volume":"129","author":"Ling","year":"2012","journal-title":"Plast Reconstr Surg"},{"key":"2021122709142254700_R5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bjoms.2009.07.019","article-title":"Long-term evaluation of donor site morbidity after free fibula transfer","volume":"48","author":"Sieg","year":"2010","journal-title":"Br J Oral Maxillofac Surg"},{"key":"2021122709142254700_R6","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1245\/s10434-009-0485-6","article-title":"Valgus ankle deformity after vascularized fibular reconstruction for oncologic disease","volume":"16","author":"Nathan","year":"2009","journal-title":"Ann Surg Oncol"},{"key":"2021122709142254700_R7","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/j.joms.2013.03.006","article-title":"Donor-site morbidity of free fibula and DCIA flaps","volume":"71","author":"Ling","year":"2013","journal-title":"J Oral Maxillofac Surg"},{"key":"2021122709142254700_R8","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1097\/scs.0b013e3180a771af","article-title":"Repair of alveolar cleft defects: Reduced morbidity with bone marrow stem cells in a resorbable matrix","volume":"18","author":"Gimbel","year":"2007","journal-title":"J Craniofac Surg"},{"key":"2021122709142254700_R9","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1126\/science.8493529","article-title":"Tissue engineering","volume":"260","author":"Langer","year":"1993","journal-title":"Science"},{"key":"2021122709142254700_R10","first-page":"167","article-title":"Combining adipose-derived stem cells, resorbable scaffolds and growth factors: An overview of tissue engineering","volume":"74","author":"S\u00e1ndor","year":"2008","journal-title":"J Can Dent Assoc"},{"key":"2021122709142254700_R11","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.2106\/00004623-200308000-00017","article-title":"Osteogenic activity of the fourteen types of human bone morphogenetic proteins","volume":"85-A","author":"Cheng","year":"2003","journal-title":"J Bone Joint Surg Am"},{"key":"2021122709142254700_R12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/00001665-200103000-00005","article-title":"Successful mandibular reconstruction using a BMP bioimplant","volume":"12","author":"Moghadam","year":"2001","journal-title":"J Craniofac Surg"},{"key":"2021122709142254700_R13","first-page":"67","article-title":"Reconstruction of 10 major mandibular defects using bioimplants containing BMP-7","volume":"74","author":"Clokie","year":"2008","journal-title":"J Can Dent Assoc"},{"key":"2021122709142254700_R14","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.tripleo.2009.10.027","article-title":"Comparison of the osteoinductivity of bioimplants containing recombinant human bone morphogenetic proteins 2 (Infuse) and 7 (OP-1)","volume":"109","author":"Barr","year":"2010","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"key":"2021122709142254700_R15","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.joms.2011.02.133","article-title":"Current trends in mesenchymal stem cell application in bone augmentation: A review of the literature","volume":"70","author":"Khojasteh","year":"2012","journal-title":"J Oral Maxillofac Surg"},{"key":"2021122709142254700_R16","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ijom.2009.01.001","article-title":"Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells","volume":"38","author":"Mesim\u00e4ki","year":"2009","journal-title":"Int J Oral Maxillofac Surg"},{"key":"2021122709142254700_R17","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1227\/NEU.0b013e31820ee24e","article-title":"Cranioplasty with adipose-derived stem cells and biomaterial: A novel method for cranial reconstruction","volume":"68","author":"Thesleff","year":"2011","journal-title":"Neurosurgery"},{"key":"2021122709142254700_R18","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.joms.2012.11.014","article-title":"Adipose stem cell (ASC) tissue engineered construct used to treat large anterior mandibular defect: A case report and review of the clinical application of GMP-level ASCs for bone regeneration","volume":"71","author":"S\u00e1ndor","year":"2013","journal-title":"J Oral Maxillofac Surg"},{"key":"2021122709142254700_R19","doi-asserted-by":"crossref","first-page":"114","DOI":"10.4103\/2231-0746.119216","article-title":"GMP-level adipose stem cells combined with computer-aided manufacturing to reconstruct mandibular ameloblastoma resection defects: Experience with 3 cases","volume":"3","author":"Wolff","year":"2013","journal-title":"Ann Maxillofac Surg"},{"key":"2021122709142254700_R20","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/jbm.a.32104","article-title":"Effect of seeding technique and scaffold material on bone formation in tissue-engineered constructs","volume":"90","author":"Schliephake","year":"2009","journal-title":"J Biomed Mater Res A"},{"key":"2021122709142254700_R21","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.joms.2008.11.020","article-title":"Engineered bone grafts and bone flaps for maxillofacial defects: State of the art","volume":"67","author":"Torroni","year":"2009","journal-title":"J Oral Maxillofac Surg"},{"key":"2021122709142254700_R22","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0140-6736(04)16935-3","article-title":"Growth and transplantation of a custom vascularised bone graft in a man","volume":"364","author":"Warnke","year":"2004","journal-title":"Lancet"},{"key":"2021122709142254700_R23","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.biomaterials.2005.07.042","article-title":"The mechanical integrity of in vivo engineered heterotopic bone","volume":"27","author":"Warnke","year":"2006","journal-title":"Biomaterials"},{"key":"2021122709142254700_R24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jcms.2011.02.003","article-title":"Repair of alveolar cleft defect with mesenchymal stem cells and platelet derived growth factors: A preliminary report","volume":"40","author":"Behnia","year":"2012","journal-title":"J Craniomaxillofac Surg"},{"key":"2021122709142254700_R25","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1054\/ijom.2001.0032","article-title":"Mandibular reconstruction with a prefabricated vascularized bone graft using recombinant human osteogenic protein-1: An experimental study in miniature pigs. Part I: Prefabrication","volume":"30","author":"Terheyden","year":"2001","journal-title":"Int J Oral Maxillofac Surg"},{"key":"2021122709142254700_R26","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1054\/ijom.2000.0008","article-title":"Mandibular reconstruction with prefabricated vascularized bone grafts using recombinant human osteogenic protein-1: An experimental study in miniature pigs. Part II: Transplantation","volume":"30","author":"Terheyden","year":"2001","journal-title":"Int J Oral Maxillofac Surg"},{"key":"2021122709142254700_R27","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1054\/ijom.2003.0500","article-title":"Prefabrication of vascularized bone grafts using recombinant human osteogenic protein-1-part 3: Dosage of rhOP-1, the use of external and internal scaffolds","volume":"33","author":"Terheyden","year":"2004","journal-title":"Int J Oral Maxillofac Surg"},{"key":"2021122709142254700_R28","doi-asserted-by":"crossref","first-page":"132","DOI":"10.2302\/kjm.54.132","article-title":"Multipotential differentiation of adipose tissue-derived stem cells","volume":"54","author":"Strem","year":"2005","journal-title":"Keio J Med"},{"key":"2021122709142254700_R29","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1080\/14653240310003026","article-title":"Adipose-derived adult stem cells: Isolation, characterization, and differentiation potential","volume":"5","author":"Gimble","year":"2003","journal-title":"Cytotherapy"},{"key":"2021122709142254700_R30","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1634\/stemcells.2005-0094","article-title":"In vitro expansion of human mesenchymal stem cells: Choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability","volume":"23","author":"Shahdadfar","year":"2005","journal-title":"Stem Cells"},{"key":"2021122709142254700_R31","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/sj.clpt.6100313","article-title":"\u201cStemness\u201d does not explain the repair of many tissues by mesenchymal stem\/multipotent stromal cells (MSCs)","volume":"82","author":"Prockop","year":"2007","journal-title":"Clin Pharmacol Ther"},{"key":"2021122709142254700_R32","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1097\/01.prs.0000204566.13979.c1","article-title":"Repair of palatal bone defects using osteogenically differentiated fat-derived stem cells","volume":"117","author":"Conejero","year":"2006","journal-title":"Plast Reconstr Surg"},{"key":"2021122709142254700_R33","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1097\/01.PRS.0000161459.90856.AB","article-title":"Tissue-engineered bone from BMP-2-transduced stem cells derived from human fat","volume":"115","author":"Dragoo","year":"2005","journal-title":"Plast Reconstr Surg"},{"key":"2021122709142254700_R34","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1016\/j.actbio.2009.04.006","article-title":"Characterization of zinc-releasing three-dimensional bioactive glass scaffolds and their effect on human adipose stem cell proliferation and osteogenic differentiation","volume":"5","author":"Haimi","year":"2009","journal-title":"Acta Biomater"},{"key":"2021122709142254700_R35","doi-asserted-by":"crossref","first-page":"2041731412467789","DOI":"10.1177\/2041731412467789","article-title":"Effects of bioactive glass S53P4 or beta tricalcium phosphate and bone morphogenetic proteins 2 and BMP-7 on osteogenic differentiation of human adipose stem cells","volume":"3","author":"Waselau","year":"2012","journal-title":"J Tissue Eng"},{"key":"2021122709142254700_R36","doi-asserted-by":"crossref","first-page":"144","DOI":"10.22203\/eCM.v025a10","article-title":"Osteogenic medium is superior to growth factors in differentiation of human adipose stem cells towards bone-forming cells in 3D culture","volume":"25","author":"Tirkkonen","year":"2013","journal-title":"Eur Cell Mater"},{"key":"2021122709142254700_R37","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/scrt165","article-title":"Effects of different serum conditions on osteogenic differentiation of human adipose stem cells in vitro","volume":"4","author":"Kyll\u00f6nen","year":"2013","journal-title":"Stem Cell Res Ther"},{"key":"2021122709142254700_R38","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1016\/S0142-9612(03)00030-9","article-title":"Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs","volume":"24","author":"Leong","year":"2003","journal-title":"Biomaterials"},{"key":"2021122709142254700_R39","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s12015-010-9193-7","article-title":"The potential of adipose stem cells in regenerative medicine","volume":"7","author":"Lindroos","year":"2011","journal-title":"Stem Cell Rev"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2013-0173","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2013-0173","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/3\/4\/530\/41888912\/stcltm_3_4_530.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/3\/4\/530\/41888912\/stcltm_3_4_530.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T21:47:57Z","timestamp":1642542477000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/3\/4\/530-540\/6388076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,20]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,2,20]]},"published-print":{"date-parts":[[2014,4,1]]}},"URL":"https:\/\/doi.org\/10.5966\/sctm.2013-0173","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718284580.793498481","asserted-by":"object"}]},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,4,1]]},"published":{"date-parts":[[2014,2,20]]}}}