Developing a biomimetic tooth bud model

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 po...

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Bibliographic Details
Published in:	Journal of tissue engineering and regenerative medicine 2017-12, Vol.11 (12), p.3326-3336
Main Authors:	Smith, Elizabeth E., Zhang, Weibo, Schiele, Nathan R., Khademhosseini, Ali, Kuo, Catherine K., Yelick, Pamela C.
Format:	Article
Language:	eng
Subjects:	Animals biodegradable hydrogel Bioengineering Biomimetics Biomimetics - methods biomineralization Cell adhesion Cell adhesion & migration Cell differentiation Cell Differentiation - drug effects cell encapsulation Cell migration Cells (biology) Dental enamel Dental implants Dental prosthetics Dental restorative materials Dentin Dentistry Elastic Modulus - drug effects Encapsulation Endothelial cells Gelatin Gelatin - pharmacology Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - metabolism Humans Hydrogels In vivo methods and tests Mesenchyme Methacrylates - pharmacology Mineralization Models, Biological progenitor cell Progenitor cells Rats, Nude Regeneration (physiology) Regenerative medicine Scaffolds Stem cells Surgical implants Sus scrofa Teeth Three dimensional models Tissue engineering Tissue Scaffolds - chemistry Tooth Germ - physiology Umbilical vein vascularization
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Summary:	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.
ISSN:	1932-6254 1932-7005