Bioengineered GelMA Tooth Bud Constructs for Future Applications in Regenerative Dentistry
Smith, Elizabeth.
2018
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Abstract: Tooth loss is a prevalent disease that affects millions of people
worldwide. Loss of natural teeth can contribute to physiological and social disadvantages
while reducing the quality of life. The exciting emerging field of Regenerative Dental
Research aims to use biologically-based tissue engineering techniques to create
bioengineered dental tissue and whole tooth replacement therapies. ... read moreThis innovative approach
will provide function and responsiveness similar to natural teeth and serve as an
alternative to currently used artificial materials. The basic goal of tissue engineering is
to repair or replace damaged or lost tissues by utilizing a combination of cells and
supportive scaffolds. The work described here is focused on the characterization and
optimization of a three-dimensional (3D) tooth bud model composed of postnatal dental
progenitor stem cells and HUVECs encapsulated within Gelatin Methacryloyl (GelMA) hydrogel
scaffold. Preliminary in vitro results showed that GelMA hydrogels can be tuned to resemble
mechanical characteristics of the natural tooth bud microenvironment. Also, encapsulated
dental cells and HUVECs exhibited increased attachment, metabolic and MMP activities
overtime. Furthermore, in vitro capillary-like networks formed within the 3D tooth bud
model. In vivo implanted tooth bud constructs demonstrated functional vascular networks
that circulated host red blood cells (RBCs) and mineralized tissue that adopted the size
and shape of the original construct. Optimization of the GelMA tooth bud model aimed to
assess the effect of various cell seeding densities and fabrication techniques. Optimized
tooth bud constructs showed evidence of many features of natural tooth buds. This includes
a putative dental epithelial stem cell (DESC) niche, a basement membrane, Wnt signaling,
bioengineered enamel knot (EK) signaling center, transit amplifying (TA) cells, and
fibrillin expression that resembled that of early tooth development. These results are the
first to report the recapitulation of the natural DESC niche and other features of natural
tooth development using postnatal dental cells. All of the results presented here, suggest
that GelMA hydrogel is a promising scaffold material that can be used in future
applications for bioengineering dental tissues and excitingly, whole teeth replacements in
humans. Future studies focus on advancing this 3D tooth bud model towards clinical
applications.
Thesis (Ph.D.)--Tufts University, 2018.
Submitted to the Dept. of Cell, Molecular & Developmental Biology.
Advisors: Pamela Yelick, and Li Zeng.
Committee: Heber Nielsen, and Lauren Black III.
Keywords: Developmental biology, Cellular biology, and Histology.read less - ID:
- ks65hq38b
- Component ID:
- tufts:26083
- To Cite:
- TARC Citation Guide EndNote