{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:09:27Z","timestamp":1790507367452,"version":"4.1.0"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006764","name":"Technische Universit\u00e4t Berlin","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006764","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Jawbone differs from other bones in many aspects, including its developmental origin and the occurrence of jawbone-specific diseases like MRONJ (medication-related osteonecrosis of the jaw). Although there is a strong need, adequate in vitro models of this unique environment are sparse to date. While previous approaches are reliant e.g. on scaffolds or spheroid culture, 3D bioprinting enables free-form fabrication of complex living tissue structures. In the present work, production of human jawbone models was realised via projection-based stereolithography. Constructs were bioprinted containing primary jawbone-derived osteoblasts and vasculature-like channel structures optionally harbouring primary endothelial cells. After 28\u00a0days of cultivation in growth medium or osteogenic medium, expression of cell type-specific markers was confirmed on both the RNA and protein level, while prints maintained their overall structure. Survival of endothelial cells in the printed channels, co-cultured with osteoblasts in medium without supplementation of endothelial growth factors, was demonstrated. Constructs showed not only mineralisation, being one of the characteristics of osteoblasts, but also hinted at differentiation to an osteocyte phenotype. These results indicate the successful biofabrication of an in vitro model of the human jawbone, which presents key features of this special bone entity and hence appears promising for application in jawbone-specific research.<\/jats:p>","DOI":"10.1038\/s41598-021-84483-4","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T11:07:32Z","timestamp":1614596852000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["3D bioprinting of tissue-specific osteoblasts and endothelial cells to model the human jawbone"],"prefix":"10.1038","volume":"11","author":[{"given":"Anna-Klara","family":"Amler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selin","family":"T\u00fcz\u00fcner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel-Andreas","family":"Geiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Elisabeth","family":"Kreuder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Nahles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Lauster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Kloke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"84483_CR1","doi-asserted-by":"publisher","first-page":"176","DOI":"10.3390\/genes9040176","volume":"9","author":"T Grix","year":"2018","unstructured":"Grix, T. et al. Bioprinting perfusion-enabled liver equivalents for advanced organ-on-a-chip applications. Genes (Basel) 9, 176 (2018).","journal-title":"Genes (Basel)"},{"key":"84483_CR2","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1089\/ten.tea.2019.0201","volume":"26","author":"T Baltazar","year":"2020","unstructured":"Baltazar, T. et al. Three dimensional bioprinting of a vascularized and perfusable skin graft using human keratinocytes, fibroblasts, pericytes, and endothelial cells. Tissue Eng. Part A 26, 227\u2013238 (2020).","journal-title":"Tissue Eng. Part A"},{"key":"84483_CR3","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1088\/1758-5082\/1\/3\/035001","volume":"1","author":"T Xu","year":"2009","unstructured":"Xu, T., Baicu, C., Aho, M., Zile, M. & Boland, T. Fabrication and characterization of bio-engineered cardiac pseudo tissues. Biofabrication 1, 20 (2009).","journal-title":"Biofabrication"},{"key":"84483_CR4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/adhm.201801501","volume":"8","author":"S Rathan","year":"2019","unstructured":"Rathan, S. et al. Fiber reinforced cartilage ECM functionalized bioinks for functional cartilage tissue engineering. Adv. Healthc. Mater. 8, 20 (2019).","journal-title":"Adv. Healthc. Mater."},{"key":"84483_CR5","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.1002\/jbm.b.34354","volume":"107","author":"T Lam","year":"2019","unstructured":"Lam, T. et al. Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue-engineered cartilage. J. Biomed. Mater. Res. Part B Appl. Biomater. 107, 2649\u20132657 (2019).","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"84483_CR6","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.tibtech.2016.03.002","volume":"34","author":"J Rouwkema","year":"2016","unstructured":"Rouwkema, J. & Khademhosseini, A. Vascularization and angiogenesis in tissue engineering: Beyond creating static networks. Trends Biotechnol. 34, 733\u2013745 (2016).","journal-title":"Trends Biotechnol."},{"key":"84483_CR7","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.tibtech.2008.04.009","volume":"26","author":"J Rouwkema","year":"2008","unstructured":"Rouwkema, J., Rivron, N. C. & van Blitterswijk, C. A. Vascularization in tissue engineering. Trends Biotechnol. 26, 434\u2013441 (2008).","journal-title":"Trends Biotechnol."},{"key":"84483_CR8","first-page":"20","volume":"20","author":"A Thomas","year":"2020","unstructured":"Thomas, A. et al. Vascular bioprinting with enzymatically degradable bioinks via multi-material projection-based stereolithography. Acta Biomater. 20, 20 (2020).","journal-title":"Acta Biomater."},{"key":"84483_CR9","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13287-018-0847-8","volume":"9","author":"A Pirosa","year":"2018","unstructured":"Pirosa, A., Gottardi, R., Alexander, P. G. & Tuan, R. S. Engineering in-vitro stem cell-based vascularized bone models for drug screening and predictive toxicology. Stem Cell Res. Ther. 9, 20 (2018).","journal-title":"Stem Cell Res. Ther."},{"key":"84483_CR10","first-page":"20","volume":"101","author":"Z Wan","year":"2020","unstructured":"Wan, Z., Zhang, P., Liu, Y., Lv, L. & Zhou, Y. Four-dimensional bioprinting: Current developments and applications in bone tissue engineering. Acta Biomater. 101, 20 (2020).","journal-title":"Acta Biomater."},{"key":"84483_CR11","first-page":"20","volume":"3","author":"EJ Sheehy","year":"2019","unstructured":"Sheehy, E. J., Kelly, D. J. & O\u2019Brien, F. J. Biomaterial-based endochondral bone regeneration: A shift from traditional tissue engineering paradigms to developmentally inspired strategies. Mater. Today Bio 3, 20 (2019).","journal-title":"Mater. Today Bio"},{"key":"84483_CR12","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.actbio.2020.03.043","volume":"108","author":"G Borciani","year":"2020","unstructured":"Borciani, G. et al. Co-culture systems of osteoblasts and osteoclasts: Simulating in vitro bone remodeling in regenerative approaches. Acta Biomater. 108, 22\u201345 (2020).","journal-title":"Acta Biomater."},{"key":"84483_CR13","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3389\/fbioe.2018.00134","volume":"6","author":"R Owen","year":"2018","unstructured":"Owen, R. & Reilly, G. C. In vitro models of bone remodelling and associated disorders. Front. Bioeng. Biotechnol. 6, 20 (2018).","journal-title":"Front. Bioeng. Biotechnol."},{"key":"84483_CR14","volume-title":"Oral Cells and Tissues","author":"PR Garant","year":"2003","unstructured":"Garant, P. R. Oral Cells and Tissues (Quintessence Publishing Company, New Malden, 2003)."},{"key":"84483_CR15","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1002\/ar.a.20396","volume":"288","author":"SS Huja","year":"2006","unstructured":"Huja, S. S., Fernandez, S. A., Hill, K. J. & Li, Y. Remodeling dynamics in the alveolar process in skeletally mature dogs. Anat. Rec. Part A Discov. Mol. Cell. Evol. Biol. 288, 1243\u20131249 (2006).","journal-title":"Anat. Rec. Part A Discov. Mol. Cell. Evol. Biol."},{"key":"84483_CR16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/nrm3254","volume":"13","author":"F Long","year":"2012","unstructured":"Long, F. Building strong bones: Molecular regulation of the osteoblast lineage. Nat. Rev. Mol. Cell Biol. 13, 27\u201338 (2012).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"84483_CR17","doi-asserted-by":"publisher","first-page":"4277","DOI":"10.1177\/0300060518788987","volume":"46","author":"H Holtmann","year":"2018","unstructured":"Holtmann, H. et al. Pathogenesis of medication-related osteonecrosis of the jaw: A comparative study of in vivo and in vitro trials. J. Int. Med. Res. 46, 4277\u20134296 (2018).","journal-title":"J. Int. Med. Res."},{"key":"84483_CR18","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.joms.2009.01.007","volume":"67","author":"MR Allen","year":"2009","unstructured":"Allen, M. R. & Burr, D. B. The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: So many hypotheses, so few data. J. Oral Maxillofac. Surg. 67, 61\u201370 (2009).","journal-title":"J. Oral Maxillofac. Surg."},{"key":"84483_CR19","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1155\/2016\/8768162","volume":"2016","author":"T Lombard","year":"2016","unstructured":"Lombard, T., Neirinckx, V., Rogister, B., Gilon, Y. & Wislet, S. Medication-related osteonecrosis of the jaw: New insights into molecular mechanisms and cellular therapeutic approaches. Stem Cells Int. 2016, 20 (2016).","journal-title":"Stem Cells Int."},{"key":"84483_CR20","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.bone.2015.01.011","volume":"74","author":"K Ogata","year":"2015","unstructured":"Ogata, K. et al. Evaluation of the therapeutic effects of conditioned media from mesenchymal stem cells in a rat bisphosphonate-related osteonecrosis of the jaw-like model. Bone 74, 95\u2013105 (2015).","journal-title":"Bone"},{"key":"84483_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjoms.2020.03.016","author":"S Basyuni","year":"2020","unstructured":"Basyuni, S., Ferro, A., Santhanam, V., Birch, M. & McCaskie, A. Systematic scoping review of mandibular bone tissue engineering. Br. J. Oral Maxillofac. Surg. https:\/\/doi.org\/10.1016\/j.bjoms.2020.03.016 (2020).","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"84483_CR22","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.bjoms.2016.05.025","volume":"54","author":"KT Mitsimponas","year":"2016","unstructured":"Mitsimponas, K. T. et al. Search for a reliable model for bisphosphonate-related osteonecrosis of the jaw: Establishment of a model in pigs and description of its histomorphometric characteristics. Br. J. Oral Maxillofac. Surg. 54, 883\u2013888 (2016).","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"84483_CR23","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.lfs.2016.03.035","volume":"152","author":"L Penolazzi","year":"2016","unstructured":"Penolazzi, L. et al. Establishment of a 3D-dynamic osteoblasts-osteoclasts co-culture model to simulate the jawbone microenvironment in vitro. Life Sci. 152, 82\u201393 (2016).","journal-title":"Life Sci."},{"key":"84483_CR24","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.tice.2018.03.009","volume":"52","author":"T Almela","year":"2018","unstructured":"Almela, T. et al. 3D printed tissue engineered model for bone invasion of oral cancer. Tissue Cell 52, 71\u201377 (2018).","journal-title":"Tissue Cell"},{"key":"84483_CR25","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1089\/ten.tec.2017.0370","volume":"24","author":"T Almela","year":"2018","unstructured":"Almela, T., Al-Sahaf, S., Bolt, R., Brook, I. M. & Moharamzadeh, K. Characterization of multilayered tissue-engineered human alveolar bone and gingival mucosa. Tissue Eng. Part C Methods 24, 99\u2013107 (2018).","journal-title":"Tissue Eng. Part C Methods"},{"key":"84483_CR26","doi-asserted-by":"publisher","first-page":"3208","DOI":"10.1016\/j.biomaterials.2013.12.088","volume":"35","author":"B Altmann","year":"2014","unstructured":"Altmann, B. et al. Differences in morphogenesis of 3D cultured primary human osteoblasts under static and microfluidic growth conditions. Biomaterials 35, 3208\u20133219 (2014).","journal-title":"Biomaterials"},{"key":"84483_CR27","doi-asserted-by":"publisher","first-page":"8947","DOI":"10.1016\/j.biomaterials.2011.08.023","volume":"32","author":"B Altmann","year":"2011","unstructured":"Altmann, B. et al. Promotion of osteoblast differentiation in 3D biomaterial micro-chip arrays comprising fibronectin-coated poly(methyl methacrylate) polycarbonate. Biomaterials 32, 8947\u20138956 (2011).","journal-title":"Biomaterials"},{"key":"84483_CR28","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/jcpe.12686","volume":"44","author":"SM Hamlet","year":"2017","unstructured":"Hamlet, S. M., Vaquette, C., Shah, A., Hutmacher, D. W. & Ivanovski, S. 3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering. J. Clin. Periodontol. 44, 428\u2013437 (2017).","journal-title":"J. Clin. Periodontol."},{"key":"84483_CR29","volume-title":"The Periodontium. The Handbook of Microscopic Anatomy","author":"HE Schroeder","year":"1986","unstructured":"Schroeder, H. E. The Periodontium. The Handbook of Microscopic Anatomy, Vol 5\/5 (Springer, Berlin, 1986)."},{"key":"84483_CR30","doi-asserted-by":"publisher","DOI":"10.2741\/3918","author":"LT Kuhn","year":"2001","unstructured":"Kuhn, L. T. Bone mineralization. Encyclop. Mater. Sci. Technol. (Sec. Ed.) https:\/\/doi.org\/10.2741\/3918 (2001).","journal-title":"Encyclop. Mater. Sci. Technol. (Sec. Ed.)"},{"key":"84483_CR31","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.dental.2016.12.005","volume":"33","author":"B Altmann","year":"2017","unstructured":"Altmann, B. et al. Cellular transcriptional response to zirconia-based implant materials. Dent. Mater. 33, 241\u2013255 (2017).","journal-title":"Dent. Mater."},{"key":"84483_CR32","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1272\/jnms.77.4","volume":"77","author":"H Orimo","year":"2010","unstructured":"Orimo, H. The mechanism of mineralization and the role of alkaline phosphatase in health and disease. J. Nippon Med. Sch. 77, 4\u201312 (2010).","journal-title":"J. Nippon Med. Sch."},{"key":"84483_CR33","volume-title":"Essentials of 3D Biofabrication and Translation","author":"A Atala","year":"2015","unstructured":"Atala, A. & Yoo, J. J. Essentials of 3D Biofabrication and Translation (Academic Press, New York, 2015)."},{"key":"84483_CR34","doi-asserted-by":"publisher","first-page":"4670","DOI":"10.1021\/cr0782729","volume":"108","author":"A George","year":"2009","unstructured":"George, A. & Veis, A. Phosphorylated proteins and control over apatite nulcleation, crystal growth and inhibition. Chem. Rev. 108, 4670\u20134693 (2009).","journal-title":"Chem. Rev."},{"key":"84483_CR35","doi-asserted-by":"publisher","first-page":"323","DOI":"10.22203\/eCM.v031a21","volume":"31","author":"MJ McGarrigle","year":"2016","unstructured":"McGarrigle, M. J., Mullen, C. A., Haugh, M. G., Voisin, M. C. & McNamara, L. M. Osteocyte differentiation and the formation of an interconnected cellular network in vitro. Eur. Cells Mater. 31, 323\u2013340 (2016).","journal-title":"Eur. Cells Mater."},{"key":"84483_CR36","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1007\/s00068-010-0030-0","volume":"36","author":"OA Trentz","year":"2010","unstructured":"Trentz, O. A. et al. Surface proteins and osteoblast markers: Characterization of human adipose tissue-derived osteogenic cells. Eur. J. Trauma Emerg. Surg. 36, 457\u2013463 (2010).","journal-title":"Eur. J. Trauma Emerg. Surg."},{"key":"84483_CR37","first-page":"20","volume":"3","author":"GR Kirkham","year":"2007","unstructured":"Kirkham, G. R. & Cartmell, S. H. Genes and proteins involved in the regulation of osteogenesis. Top. Tissue Eng. 3, 20 (2007).","journal-title":"Top. Tissue Eng."},{"key":"84483_CR38","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1088\/1758-5090\/aa53bd","volume":"9","author":"C McBeth","year":"2017","unstructured":"McBeth, C. et al. 3D bioprinting of GelMA scaffolds triggers mineral deposition by primary human osteoblasts. Biofabrication 9, 2 (2017).","journal-title":"Biofabrication"},{"key":"84483_CR39","first-page":"20","volume":"6","author":"JY Park","year":"2014","unstructured":"Park, J. Y. et al. A comparative study on collagen type i and hyaluronic acid dependent cell behavior for osteochondral tissue bioprinting. Biofabrication 6, 20 (2014).","journal-title":"Biofabrication"},{"key":"84483_CR40","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1016\/j.biomaterials.2009.10.040","volume":"31","author":"Y Liu","year":"2010","unstructured":"Liu, Y. & Chan-Park, M. B. A biomimetic hydrogel based on methacrylated dextran-graft-lysine and gelatin for 3D smooth muscle cell culture. Biomaterials 31, 1158\u20131170 (2010).","journal-title":"Biomaterials"},{"key":"84483_CR41","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1002\/adhm.201501033","volume":"5","author":"DF Duarte Campos","year":"2016","unstructured":"Duarte Campos, D. F. et al. Bioprinting organotypic hydrogels with improved mesenchymal stem cell remodeling and mineralization properties for bone tissue engineering. Adv. Healthc. Mater. 5, 1336\u20131345 (2016).","journal-title":"Adv. Healthc. Mater."},{"key":"84483_CR42","doi-asserted-by":"publisher","first-page":"8927","DOI":"10.1016\/j.biomaterials.2014.06.047","volume":"35","author":"C Branco da Cunha","year":"2014","unstructured":"Branco da Cunha, C. et al. Influence of the stiffness of three-dimensional alginate\/collagen-I interpenetrating networks on fibroblast biology. Biomaterials 35, 8927\u20138936 (2014).","journal-title":"Biomaterials"},{"key":"84483_CR43","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/nmat2732","volume":"9","author":"N Huebsch","year":"2010","unstructured":"Huebsch, N. et al. Harnessing traction-mediated manipulation of the cellmatrix interface to control stem-cell fate. Nat. Mater. 9, 518\u2013526 (2010).","journal-title":"Nat. Mater."},{"key":"84483_CR44","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/nmat3586","volume":"12","author":"S Khetan","year":"2013","unstructured":"Khetan, S. et al. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat. Mater. 12, 458\u2013465 (2013).","journal-title":"Nat. Mater."},{"key":"84483_CR45","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1088\/1758-5090\/ab6a1d","volume":"12","author":"I Chiesa","year":"2020","unstructured":"Chiesa, I. et al. Endothelial cells support osteogenesis in an in vitro vascularized bone model developed by 3D bioprinting. Biofabrication 12, 20 (2020).","journal-title":"Biofabrication"},{"key":"84483_CR46","first-page":"20","volume":"12","author":"AG Mikos","year":"2006","unstructured":"Mikos, A. G. et al. Engineering complex tissues. Tissue Eng. 12, 20 (2006).","journal-title":"Tissue Eng."},{"key":"84483_CR47","doi-asserted-by":"publisher","first-page":"3311","DOI":"10.1073\/pnas.0905445107","volume":"107","author":"O Tsigkou","year":"2010","unstructured":"Tsigkou, O. et al. Engineered vascularized bone grafts. Proc. Natl. Acad. Sci. USA 107, 3311\u20133316 (2010).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"84483_CR48","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.archoralbio.2007.04.007","volume":"52","author":"BW Park","year":"2007","unstructured":"Park, B. W., Hah, Y. S., Kim, D. R., Kim, J. R. & Byun, J. H. Osteogenic phenotypes and mineralization of cultured human periosteal-derived cells. Arch. Oral Biol. 52, 983\u2013989 (2007).","journal-title":"Arch. Oral Biol."},{"key":"84483_CR49","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1016\/j.actbio.2010.12.027","volume":"7","author":"L Klouda","year":"2011","unstructured":"Klouda, L. et al. Thermoresponsive, in situ cross-linkable hydrogels based on N-isopropylacrylamide fabrication, characterization and mesenchymal stem cell encapsulation. Acta Biomater. 7, 1460\u20131467 (2011).","journal-title":"Acta Biomater."},{"key":"84483_CR50","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.bone.2015.05.046","volume":"82","author":"ML Zoch","year":"2016","unstructured":"Zoch, M. L., Clemens, T. L. & Riddle, R. C. New insights into the biology of osteocalcin. Bone 82, 42\u201349 (2016).","journal-title":"Bone"},{"key":"84483_CR51","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1002\/jbm.a.34937","volume":"102","author":"EM Czekanska","year":"2014","unstructured":"Czekanska, E. M., Stoddart, M. J., Ralphs, J. R., Richards, R. G. & Hayes, J. S. A phenotypic comparison of osteoblast cell lines versus human primary osteoblasts for biomaterials testing. J. Biomed. Mater. Res. Part A 102, 2636\u20132643 (2014).","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"84483_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-415853-5.00011-X","volume-title":"The Regulatory Role of Matrix Proteins in Mineralization of Bone. Osteoporosis","author":"AL Boskey","year":"2013","unstructured":"Boskey, A. L. & Robey, P. G. The Regulatory Role of Matrix Proteins in Mineralization of Bone. Osteoporosis 4th edn. (Elsevier, New York, 2013). https:\/\/doi.org\/10.1016\/B978-0-12-415853-5.00011-X.","edition":"4"},{"key":"84483_CR53","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1088\/1758-5090\/aacb42","volume":"10","author":"SW Sawyer","year":"2018","unstructured":"Sawyer, S. W. et al. Perfusion directed 3D mineral formation within cell-laden hydrogels. Biofabrication 10, 20 (2018).","journal-title":"Biofabrication"},{"key":"84483_CR54","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1177\/2041731414539344","volume":"5","author":"LA Castillo Diaz","year":"2014","unstructured":"Castillo Diaz, L. A., Saiani, A., Gough, J. E. & Miller, A. F. Human osteoblasts within soft peptide hydrogels promote mineralisation in vitro. J. Tissue Eng. 5, 20 (2014).","journal-title":"J. Tissue Eng."},{"key":"84483_CR55","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1016\/j.jcms.2015.07.030","volume":"43","author":"M Wein","year":"2015","unstructured":"Wein, M. et al. Pilot investigation of the molecular discrimination of human osteoblasts from different bone entities. J. Cranio-Maxillofac. Surg. 43, 1487\u20131493 (2015).","journal-title":"J. Cranio-Maxillofac. Surg."},{"key":"84483_CR56","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1006\/excr.1997.3501","volume":"232","author":"F Liu","year":"1997","unstructured":"Liu, F., Malaval, L. & Aubin, J. E. The mature osteoblast phenotype is characterized by extensive plasticity. Exp. Cell Res. 232, 97\u2013105 (1997).","journal-title":"Exp. Cell Res."},{"key":"84483_CR57","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s00441-009-0832-8","volume":"339","author":"T Komori","year":"2010","unstructured":"Komori, T. Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell Tissue Res. 339, 189\u2013195 (2010).","journal-title":"Cell Tissue Res."},{"key":"84483_CR58","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1177\/0022034511435260","volume":"91","author":"RJ Miron","year":"2012","unstructured":"Miron, R. J. & Zhang, Y. F. Osteoinduction: A review of old concepts with new standards. J. Dent. Res. 91, 736\u2013744 (2012).","journal-title":"J. Dent. Res."},{"key":"84483_CR59","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/BF00218209","volume":"248","author":"G Jundt","year":"1987","unstructured":"Jundt, G., Bergh\u00e4user, K., Termine, J. D. & Schulz, A. Osteonectin\u2014a differentiation marker of bone cells. Cell Tissue Res. 248, 409\u2013415 (1987).","journal-title":"Cell Tissue Res."},{"key":"84483_CR60","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1101\/gad.13.8.1025","volume":"13","author":"P Ducy","year":"1999","unstructured":"Ducy, P. et al. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev. 13, 1025\u20131036 (1999).","journal-title":"Genes Dev."},{"key":"84483_CR61","first-page":"20","volume":"9","author":"D Marolt","year":"2014","unstructured":"Marolt, D., Rode, M., Kregar-Velikonja, N., Jeras, M. & Knezevic, M. Primary human alveolar bone cells isolated from tissue samples acquired at periodontal surgeries exhibit sustained proliferation and retain osteogenic phenotype during in vitro expansion. PloS\u00a0One 9, 20 (2014).","journal-title":"PloS\u00a0One"},{"key":"84483_CR62","first-page":"1","volume":"21","author":"C Kelder","year":"2020","unstructured":"Kelder, C., Kleverlaan, C. J., Gilijamse, M., Bakker, A. D. & de Vries, T. J. Cells derived from human long bone appear more differentiated and more actively stimulate osteoclastogenesis compared to alveolar bone-derived cells. Int. J. Mol. Sci. 21, 1\u201317 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"84483_CR63","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.bone.2009.11.032","volume":"46","author":"Y Bala","year":"2010","unstructured":"Bala, Y., Farlay, D., Delmas, P. D., Meunier, P. J. & Boivin, G. Time sequence of secondary mineralization and microhardness in cortical and cancellous bone from ewes. Bone 46, 1204\u20131212 (2010).","journal-title":"Bone"},{"key":"84483_CR64","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/jcp.25875","volume":"233","author":"S Pagani","year":"2018","unstructured":"Pagani, S. et al. An advanced tri-culture model to evaluate the dynamic interplay among osteoblasts, osteoclasts, and endothelial cells. J. Cell. Physiol. 233, 291\u2013301 (2018).","journal-title":"J. Cell. Physiol."},{"key":"84483_CR65","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1021\/bm990017d","volume":"1","author":"AI Van Den Bulcke","year":"2000","unstructured":"Van Den Bulcke, A. I. et al. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromol 1, 31\u201338 (2000).","journal-title":"Biomacromol"},{"key":"84483_CR66","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/srep31036","volume":"6","author":"H Shirahama","year":"2016","unstructured":"Shirahama, H., Lee, B. H., Tan, L. P. & Cho, N. J. Precise tuning of facile one-pot gelatin methacryloyl (GelMA) synthesis. Sci. Rep. 6, 20 (2016).","journal-title":"Sci. Rep."},{"key":"84483_CR67","first-page":"1","volume":"12","author":"MT Poldervaart","year":"2017","unstructured":"Poldervaart, M. T. et al. 3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity. PLoS\u00a0One 12, 1\u201315 (2017).","journal-title":"PLoS\u00a0One"},{"key":"84483_CR68","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1002\/macp.1991.021921010","volume":"192","author":"T Majima","year":"1991","unstructured":"Majima, T. & Schnabel, W. Phenyl-2,4,6-trimethylbenzoylphosphinates as water-soluble photoinitiators. Generation and reactivity of O=b(C6Hs)(O\u2013) radical anions. Makromol. Chem. Macromol. Chem. Phys. 192, 2307\u20132315 (1991).","journal-title":"Makromol. Chem. Macromol. Chem. Phys."},{"key":"84483_CR69","doi-asserted-by":"publisher","first-page":"6702","DOI":"10.1016\/j.biomaterials.2009.08.055","volume":"30","author":"BD Fairbanks","year":"2009","unstructured":"Fairbanks, B. D., Schwartz, M. P., Bowman, C. N. & Anseth, K. S. Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: Polymerization rate and cytocompatibility. Biomaterials 30, 6702\u20136707 (2009).","journal-title":"Biomaterials"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84483-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84483-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84483-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T04:33:53Z","timestamp":1670042033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84483-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["84483"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-84483-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,1]]},"assertion":[{"value":"30 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"AKA, AT, ST, TL, MAG, AEK, and CP are or have been employees at Cellbricks GmbH. LK is shareholder of Cellbricks GmbH. Rest of authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4876"}}