{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:02:35Z","timestamp":1785729755071,"version":"3.56.0"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Plovdiv, Bulgaria","award":["PMD 01\/2022"],"award-info":[{"award-number":["PMD 01\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Salivary gland biofabrication represents a promising avenue in regenerative medicine, aiming to address the challenges of salivary gland dysfunction caused by various factors such as autoimmune diseases and radiotherapy. This review examines the current state of bioprinting technology, biomaterials, and tissue engineering strategies in the context of creating functional, implantable salivary gland constructs. Key considerations include achieving vascularization for proper nutrient supply, maintaining cell viability and functionality during printing, and promoting tissue maturation and integration with surrounding tissues. Despite the existing challenges, recent advancements offer significant potential for the development of personalized therapeutic options to treat salivary gland disorders. Continued research and innovation in this field hold the potential to revolutionize the management of salivary gland conditions, improving patient outcomes and quality of life. This systematic review covers publications from 2018 to April 2024 and was conducted on four databases: Google Scholar, PubMed, EBSCOhost, and Web of Science. The key features necessary for the successful creation, implantation and functioning of bioprinted salivary glands are addressed.<\/jats:p>","DOI":"10.3390\/jfb15060151","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T03:51:45Z","timestamp":1717386705000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unlocking the Future: Bioprinting Salivary Glands\u2014From Possibility to Reality"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1287-930X","authenticated-orcid":false,"given":"Dobromira","family":"Shopova","sequence":"first","affiliation":[{"name":"Department of Prosthetic Dentistry, Faculty of Dental Medicine, Medical University-Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoniya","family":"Yaneva","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics, Biostatistics and eLearning, Faculty of Public Health, Medical University-Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7674-6074","authenticated-orcid":false,"given":"Anna","family":"Mihaylova","sequence":"additional","affiliation":[{"name":"Department of Healthcare Management, Faculty of Public Health, Medical University-Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atanaska","family":"Dinkova","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Faculty of Dental Medicine, Medical University-Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-8854","authenticated-orcid":false,"given":"Desislava","family":"Bakova","sequence":"additional","affiliation":[{"name":"Department of Healthcare Management, Faculty of Public Health, Medical University-Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tamay, D.G., Dursun Usal, T., Alagoz, A.S., Yucel, D., Hasirci, N., and Hasirci, V. (2019). 3D and 4D printing of polymers for tissue engineering applications. Front. Bioeng. Biotechnol., 7.","DOI":"10.3389\/fbioe.2019.00164"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nbt.2958","article-title":"3D bioprinting of tissues and organs","volume":"32","author":"Murphy","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Matichescu, A., Ardelean, L.C., Rusu, L.C., Craciun, D., Bratu, E.A., Babucea, M., and Leretter, M. (2020). Advanced biomaterials and techniques for oral tissue engineering and regeneration\u2014A review. Materials, 13.","DOI":"10.3390\/ma13225303"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rodriguez-Salvador, M., and Ruiz-Cantu, L. (2019). Revealing emerging science and technology research for dentistry applications of 3D bioprinting. Int. J. Bioprinting, 5.","DOI":"10.18063\/ijb.v5i1.170"},{"key":"ref_5","first-page":"S57.e1","article-title":"Salivary dysfunction associated with systemic diseases: Systematic review and clinical management recommendations","volume":"103","author":"Sollecito","year":"2007","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00520-010-0827-8","article-title":"A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: Prevalence, severity and impact on quality of life","volume":"18","author":"Jensen","year":"2010","journal-title":"Support. Care Cancer"},{"key":"ref_7","first-page":"465","article-title":"Diagnosis and management of Sj\u00f6gren syndrome","volume":"79","author":"Kruszka","year":"2009","journal-title":"Am. Fam. Physician"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yoo, C., Vines, J.B., Alexander, G., Murdock, K., Hwang, P., and Jun, H.W. (2014). Adult stem cells and tissue engineering strategies for salivary gland regeneration: A review. Biomater. Res., 18.","DOI":"10.1186\/2055-7124-18-9"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10856-022-06676-1","article-title":"Stem cells and common biomaterials in dentistry: A review study","volume":"33","author":"Mosaddad","year":"2022","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"72","DOI":"10.5005\/jcdp-9-3-72","article-title":"Saliva composition and functions: A comprehensive review","volume":"9","author":"Gregio","year":"2008","journal-title":"J. Contemp. Dent. Pr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1067\/mpr.2001.113778","article-title":"A review of saliva: Normal composition, flow, and function","volume":"85","author":"Humphrey","year":"2001","journal-title":"J. Prosthet. Dent."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/sj.bdj.4807861","article-title":"Saliva: Its secretion, composition and functions","volume":"172","author":"Edgar","year":"1992","journal-title":"Br. Dent. J."},{"key":"ref_13","first-page":"1552","article-title":"Composition and function of saliva: A review","volume":"9","author":"Fatima","year":"2020","journal-title":"World J. Pharm. Pharm. Sci"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jdent.2004.10.009","article-title":"Health benefits of saliva: A review","volume":"33","author":"Dodds","year":"2005","journal-title":"J. Dent."},{"key":"ref_15","first-page":"140","article-title":"The composition, function and role of saliva in maintaining oral health: A review","volume":"220","author":"Kumar","year":"2017","journal-title":"Proteins"},{"key":"ref_16","unstructured":"Adine, C., and Ferreira, J. (2020). Organ Tissue Engineering, Springer."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-3-030-11096-3_9","article-title":"Unveiling stem cell heterogeneity toward the development of salivary gland regenerative strategies","volume":"1123","author":"Urkasemsin","year":"2019","journal-title":"Stem Cells Heterog. Nov. Concepts"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hajiabbas, M., D\u2019Agostino, C., Simi\u0144ska-Stanny, J., Tran, S.D., Shavandi, A., and Delporte, C. (2022). Bioengineering in salivary gland regeneration. J. Biomed. Sci., 29.","DOI":"10.1186\/s12929-022-00819-w"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13643-021-01671-z","article-title":"How to properly use the PRISMA Statement","volume":"10","author":"Aromataris","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1021\/acsabm.4c00028","article-title":"Bioengineered Salivary Gland Microtissues\u2500 A Review of 3D Cellular Models and their Applications","volume":"7","author":"Pillai","year":"2024","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Muallah, D., Matschke, J., Kappler, M., Kroschwald, L.M., Lauer, G., and Eckert, A.W. (2023). Dental Pulp Stem Cells for Salivary Gland Regeneration\u2014Where Are We Today?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108664"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rose, S.C., Larsen, M., Xie, Y., and Sharfstein, S.T. (2024). Salivary Gland Bioengineering. Bioengineering, 11.","DOI":"10.3390\/bioengineering11010028"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41536-020-00115-x","article-title":"The evolving definition of salivary gland stem cells","volume":"6","author":"Rocchi","year":"2021","journal-title":"NPJ Regen. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Almansoori, A.A., Kim, B., Lee, J.H., and Tran, S.D. (2020). Tissue engineering of oral mucosa and salivary gland: Disease modeling and clinical applications. Micromachines, 11.","DOI":"10.3390\/mi11121066"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9995","DOI":"10.1021\/acs.analchem.0c05165","article-title":"Raman spectroscopy-based 3D analysis of odontogenic differentiation of human dental pulp stem cell spheroids","volume":"93","author":"Kim","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1007\/s12015-021-10326-4","article-title":"Hypes and hopes of stem cell therapies in dentistry: A review","volume":"18","author":"Casasco","year":"2022","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4216","DOI":"10.1038\/s41467-018-06469-7","article-title":"Generation of orthotopically functional salivary gland from embryonic stem cells","volume":"9","author":"TaTanaka","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13287-020-01628-4","article-title":"Generation of functional salivary gland tissue from human submandibular gland stem\/progenitor cells","volume":"11","author":"Sui","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/dvdy.78","article-title":"Fibronectin-induced ductal formation in salivary gland self-organization model","volume":"248","author":"Farahat","year":"2019","journal-title":"Dev. Dyn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.biomaterials.2018.06.011","article-title":"Engineering innervated secretory epithelial organoids by magnetic three-dimensional bioprinting for stimulating epithelial growth in salivary glands","volume":"180","author":"Adine","year":"2018","journal-title":"Biomaterials"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1038\/s41556-022-01007-6","article-title":"Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication","volume":"24","author":"Tanaka","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41368-023-00224-5","article-title":"Autologous mesenchymal stem cells offer a new paradigm for salivary gland regeneration","volume":"15","author":"Marinkovic","year":"2023","journal-title":"Int. J. Oral. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pillai, S., Munguia-Lopez, J.G., and Tran, S.D. (2022). Hydrogels for salivary gland tissue engineering. Gels, 8.","DOI":"10.3390\/gels8110730"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wu, D.T., Munguia-Lopez, J.G., Cho, Y.W., Ma, X., Song, V., Zhu, Z., and Tran, S.D. (2021). Polymeric scaffolds for dental, oral, and craniofacial regenerative medicine. Molecules, 26.","DOI":"10.3390\/molecules26227043"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1177\/0022034520964784","article-title":"Trimers conjugated to fibrin hydrogels promote salivary gland function","volume":"100","author":"Nam","year":"2021","journal-title":"J. Dent. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Pham, H.M., Munguia-Lopez, J.G., Kinsella, J.M., and Tran, S.D. (2020). The optimization of a novel hydrogel\u2014Egg white-alginate for 2.5 D tissue engineering of salivary spheroid-like structure. Molecules, 25.","DOI":"10.3390\/molecules25235751"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Saska, S., Pilatti, L., Blay, A., and Shibli, J.A. (2021). Bioresorbable Polymers: Advanced Materials and 4D Printing for Tissue Engineering. Polymers, 13.","DOI":"10.3390\/polym13040563"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2300128","DOI":"10.1002\/adtp.202300128","article-title":"Hydrogels in dental medicine","volume":"7","author":"Chen","year":"2024","journal-title":"Adv. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chocholata, P., Kulda, V., and Babuska, V. (2019). Fabrication of Scaffolds for Bone-Tissue Regeneration. Materials, 12.","DOI":"10.3390\/ma12040568"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Andia, I., Perez-Valle, A., Del Amo, C., and Maffulli, N. (2020). Freeze-Drying of Platelet-Rich Plasma: The Quest for Standardization. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186904"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rahman, S.U., Nagrath, M., Ponnusamy, S., and Arany, P.R. (2018). Nanoscale and Macroscale Scaffolds with Controlled-Release Polymeric Systems for Dental Craniomaxillofacial Tissue Engineering. Materials, 11.","DOI":"10.3390\/ma11081478"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tao, O., Kort-Mascort, J., Lin, Y., Pham, H.M., Charbonneau, A.M., ElKashty, O.A., Kinsella, J.M., and Tran, S.D. (2019). The applications of 3D printing for craniofacial tissue engineering. Micromachines, 10.","DOI":"10.3390\/mi10070480"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s42825-023-00129-3","article-title":"3D bioprinting of collagen-based materials for oral medicine","volume":"5","author":"Yang","year":"2023","journal-title":"Collagen Leather."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Latimer, J.M., Maekawa, S., Yao, Y., Wu, D.T., Chen, M., and Giannobile, W.V. (2021). Regenerative medicine technologies to treat dental, oral, and craniofacial defects. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.704048"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1002\/term.2932","article-title":"Oxygen and nutrient delivery in tissue engineering: Approaches to graft vascularization","volume":"13","author":"Rademakers","year":"2019","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Nesic, D., Durual, S., Marger, L., Mekki, M., Sailer, I., and Scherrer, S.S. (2020). Could 3D printing be the future for oral soft tissue regeneration?. Bioprinting, 20.","DOI":"10.1016\/j.bprint.2020.e00100"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tomasina, C., Bodet, T., Mota, C., Moroni, L., and Camarero-Espinosa, S. (2019). Bioprinting Vasculature: Materials, Cells and Emergent Techniques. Materials, 12.","DOI":"10.3390\/ma12172701"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.actbio.2019.03.016","article-title":"Upgrading prevascularization in tissue engineering: A review of strategies for promoting highly organized microvascular network formation","volume":"95","author":"Sharma","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10430","DOI":"10.1038\/s41598-018-28715-0","article-title":"Engineering biofunctional in vitro vessel models using a multilayer bioprinting technique","volume":"8","author":"Schoeneberg","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Porcheri, C., and Mitsiadis, T.A. (2019). Physiology, Pathology and Regeneration of Salivary Glands. Cells, 8.","DOI":"10.3390\/cells8090976"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3389\/fphar.2020.00222","article-title":"P2 receptors as therapeutic targets in the salivary gland: From physiology to dysfunction","volume":"11","author":"Khalafalla","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/joor.12664","article-title":"Salivary secretion in health and disease","volume":"45","author":"Pedersen","year":"2018","journal-title":"J. Oral Rehabil."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1089\/ten.tea.2020.0184","article-title":"Building a functional salivary gland for cell-based therapy: More than secretory epithelial acini","volume":"26","author":"Barrows","year":"2020","journal-title":"Tissue Eng. Part A"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nmeth.4538","article-title":"Organoids: The body builders","volume":"15","author":"Eisenstein","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1177\/0022034520983808","article-title":"Oral organoids: Progress and challenges","volume":"100","author":"Gao","year":"2021","journal-title":"J. Dent. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"27226","DOI":"10.1038\/srep27226","article-title":"4D printing smart biomedical scaffolds with novel soybean oil epoxidized acrylate","volume":"6","author":"Miao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yang, Q., Gao, B., and Xu, F. (2020). Recent advances in 4D bioprinting. Biotechnol. J., 15.","DOI":"10.1002\/biot.201900086"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1800412","DOI":"10.1002\/adhm.201800412","article-title":"4D biofabrication: Materials, methods, and applications","volume":"7","author":"Ionov","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1089\/ten.teb.2021.0004","article-title":"Strategies of prevascularization in tissue engineering and regeneration of craniofacial tissues","volume":"28","author":"Xu","year":"2022","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sasmal, P., Datta, P., Wu, Y., and Ozbolat, I.T. (2018). 3D bioprinting for modelling vasculature. Microphysiol. Syst., 2.","DOI":"10.21037\/mps.2018.10.02"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1021\/acsabm.1c00979","article-title":"Tissue engineered neurovascularization strategies for craniofacial tissue regeneration","volume":"5","author":"Li","year":"2021","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1089\/ten.teb.2020.0149","article-title":"Trends in salivary gland tissue engineering: From stem cells to secretome and organoid bioprinting","volume":"27","author":"Chansaenroj","year":"2021","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Li, Z., Yue, M., Liu, Y., Zhang, P., Qing, J., Liu, H., and Zhou, Y. (2022). Advances of engineered hydrogel organoids within the stem cell field: A systematic review. Gels, 8.","DOI":"10.3390\/gels8060379"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9922597","DOI":"10.1155\/2021\/9922597","article-title":"Organoid models for salivary gland biology and regenerative medicine","volume":"2021","author":"Zhao","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Cal\u00e0, G., Sina, B., De Coppi, P., Giobbe, G.G., and Gerli, M.F.M. (2023). Primary human organoids models: Current progress and key milestones. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1058970"}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/15\/6\/151\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:52:26Z","timestamp":1760107946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/15\/6\/151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,1]]},"references-count":65,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["jfb15060151"],"URL":"https:\/\/doi.org\/10.3390\/jfb15060151","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,1]]}}}