# Bioengineered 3D tooth germs for tooth regeneration in vitro and in vivo

> **NIH NIH R56** · UNIVERSITY OF WASHINGTON · 2024 · $443,576

## Abstract

Project Summary
Dental decay and tooth loss are common problems. Bridges and implants are the primary treatment options
but cannot completely restore the tooth biology and function. Although using cells from embryo to rebuild a
functional bioengineered tooth has been demonstrated in animals, little is known in how to use a cell source to
regenerate teeth in humans. Human induced pluripotent stem cells (hiPSCs) hold tremendous promise to
regenerate teeth because of their near-unlimited regenerative capacity that can produce almost any tissues in
the body. However, stem cell-based therapy has been hindered by our limited ability to provide an adequate
microenvironment for stem cell renewal and differentiation and lack of understanding on the key signals
required to regulate cell fate and cell-cell interaction during tooth development. The proposed research aims to
develop a well-defined, feeder-free 3D material microenvironment for regulating self-renewal and
differentiation of hiPSCs into odontogenic epithelial stem cells (OESCs) and neural crest cells (NCCs), and to
co-culture OESCs with NCCs for tooth regeneration. The proposed 3D construct is made of a hybrid scaffold
of chitosan and alginate (CA), two natural polymers that have a proxy structure of glycosaminoglycans, a
major component of the native extracellular matrix (ECM). Natural polymer-based materials are clinically
preferable over synthetic polymers or protein-based materials due to their excellent biocompatibility,
biodegradability, and minimal immunogenicity. In addition, unlike synthetic polymers, The CA scaffold can be
readily decomposed in cell-compatible solutions thus posing no harm to grown stem cells facilitating
subsequent use and analysis. The specific aims of the proposed research are to (1) investigate how material
composition and mechanical properties regulate stem cell renewal and if CA scaffolds optimized for stem cell
renewal can support long-term growth of OESCs and NCCs in vitro; (2) differentiate hiPSCs into OESCs and
NCCs, and identify proper reciprocal interactions of epithelial-mesenchymal stem cells for odontogenesis by
co-culturing OESCs with NCCs in CA scaffolds; (3) enable odontogenic differentiation of hiPSCs and tooth
tissue formation in an orthotopic mouse model. Successful completion of the proposed research would make a
profound impact on stem-cell biology and technology and on human tooth tissue regeneration. Studies of tooth
formation from human pluripotent stem cells will enhance the research community’s understanding on the fate
decisions of tooth-specific lineages in odontogenesis and the epithelial-mesenchymal interactions required
during tooth development.

## Key facts

- **NIH application ID:** 11139200
- **Project number:** 1R56DE032720-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Miqin Zhang
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $443,576
- **Award type:** 1
- **Project period:** 2024-09-05 → 2026-09-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11139200

## Citation

> US National Institutes of Health, RePORTER application 11139200, Bioengineered 3D tooth germs for tooth regeneration in vitro and in vivo (1R56DE032720-01A1). Retrieved via AI Analytics 2026-07-26 from https://api.ai-analytics.org/grant/nih/11139200. Licensed CC0.

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