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Developing a biomimetic tooth bud model. 2017

Elizabeth E Smith, and Weibo Zhang, and Nathan R Schiele, and Ali Khademhosseini, and Catherine K Kuo, and Pamela C Yelick
Department of Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, USA.

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.

UI MeSH Term Description Entries
D008689 Methacrylates Acrylic acids or acrylates which are substituted in the C-2 position with a methyl group. Methacrylate
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011923 Rats, Nude A mutant strain of Rattus norvegicus without a thymus and with depressed or absent T-cell function. This strain of rats may have a small amount of hair at times, but then lose it. Athymic Rats,Nude Rats,Rats, Athymic,Athymic Rat,Nude Rat,Rat, Athymic,Rat, Nude
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D005780 Gelatin A product formed from skin, white connective tissue, or bone COLLAGEN. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. Gelafusal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014083 Tooth Germ The collective tissues from which an entire tooth is formed, including the DENTAL SAC; ENAMEL ORGAN; and DENTAL PAPILLA. (From Jablonski, Dictionary of Dentistry, 1992) Germ, Tooth,Germs, Tooth,Tooth Germs
D054457 Tissue Scaffolds Cell growth support structures composed of BIOCOMPATIBLE MATERIALS. They are specially designed solid support matrices for cell attachment in TISSUE ENGINEERING and GUIDED TISSUE REGENERATION uses. Tissue Scaffolding,Scaffold, Tissue,Scaffolding, Tissue,Scaffoldings, Tissue,Scaffolds, Tissue,Tissue Scaffold,Tissue Scaffoldings
D055119 Elastic Modulus Numerical expression indicating the measure of stiffness in a material. It is defined by the ratio of stress in a unit area of substance to the resulting deformation (strain). This allows the behavior of a material under load (such as bone) to be calculated. Young Modulus,Modulus of Elasticity,Young's Modulus,Elasticity Modulus,Modulus, Elastic,Modulus, Young,Modulus, Young's,Youngs Modulus

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