title: Developing a biomimetic tooth bud model.
abstract: A long-term goal is to bioengineer, fully functional, living teeth for regenerative medicine and dentistry applications. Biologically based replacement teeth would avoid insufficiencies of the currently used dental implants. Using natural tooth development as a guide, a model was fabricated using post-natal porcine dental epithelial (pDE), porcine dental mesenchymal (pDM) progenitor cells, and human umbilical vein endothelial cells (HUVEC) encapsulated within gelatin methacrylate (GelMA) hydrogels. Previous publications have shown that post-natal DE and DM cells seeded onto synthetic scaffolds exhibited mineralized tooth crowns composed of dentin and enamel. However, these tooth structures were small and formed within the pores of the scaffolds. The present study shows that dental cell-encapsulated GelMA constructs can support mineralized dental tissue formation of predictable size and shape. Individually encapsulated pDE or pDM cell GelMA constructs were analysed to identify formulas that supported pDE and pDM cell attachment, spreading, metabolic activity, and neo-vasculature formation with co-seeded endothelial cells (HUVECs). GelMa constructs consisting of pDE-HUVECS in 3% GelMA and pDM-HUVECs within 5% GelMA supported dental cell differentiation and vascular mineralized dental tissue formation in vivo. These studies are the first to demonstrate the use of GelMA hydrogels to support the formation of post-natal dental progenitor cell-derived mineralized and functionally vascularized tissues of specified size and shape. These results introduce a novel three-dimensional biomimetic tooth bud model for eventual bioengineered tooth replacement teeth in humans. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, USA.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Smith
authors.affiliation: Department of Orthodontics, Tufts University School of Dental Medicine, Boston, MA, USA.
authors.forename: Weibo
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Tufts University, Science and Technology Center, Medford, MA, USA.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Schiele
authors.affiliation: Division of Health Sciences and Technology, Harvard-MIT, Biomaterials Innovations Research Center, and Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: Center for Musculoskeletal Research Genetics, Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA.
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Kuo
authors.affiliation: Department of Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, USA.|Department of Orthodontics, Tufts University School of Dental Medicine, Boston, MA, USA.|Department of Biomedical Engineering, Tufts University, Science and Technology Center, Medford, MA, USA.
authors.forename: Pamela C
authors.initials: PC
authors.lastname: Yelick
mesh_terms: D000818:Animals; D057005:Bioengineering; D032701:Biomimetics / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D055119:Elastic Modulus / Q000187:drug effects; D005780:Gelatin / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008689:Methacrylates / Q000494:pharmacology; D008954:Models, Biological; D011923:Rats, Nude; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry; D014083:Tooth Germ / Q000502:physiology*
chemical_list: D008689:Methacrylates; D005780:Gelatin
keywords: biodegradable hydrogel; biomineralization; cell differentiation; cell encapsulation; progenitor cell; vascularization