# Microengineering the Dental Pulp Vascular Microenvironment

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $503,137

## Abstract

Project Summary:
Dental caries is an infectious disease affecting approximately 90% of adults worldwide. Late stages of caries
affect the dental pulp, leading to tissue necrosis and ultimately requiring root canal therapy. Typically, root
canals in permanent teeth are treated by removing the necrotic tissue and replacing it with an artificial material.
Regenerative endodontics has been proposed as an improved treatment option for these conditions. However,
without controllable strategies to engineer the pulp vasculature, effective pulp regeneration is virtually
impossible. It has been recently demonstrated that a functional vasculature can be engineered by culturing
endothelial cells and stem cells from various sources in the correct microenvironmental conditions. However,
the precise requirements specific to regenerating the pulp vasculature remain poorly understood. This project
will systematically investigate three overlapping aspects that we propose are key determinants to regenerate
the pulp vasculature: (1) matrix physical and mechanical properties, (2) composition, and (3) microarchitecture.
In aim 1 we will investigate the contributions of different physical and mechanical properties to the ability of
human endothelial colony forming cells (ECFCs) and dental pulp stem cells (DPSCs) to form microvascular
networks when embedded in hydrogels that can be photo-crosslinked to have their properties systematically
adjusted. We will then engineer pulp tissue-constructs that are pre-vascularized with pre-fabricated endothelial
microchannels to enhance pulp regeneration in full-length root canals in-vivo. In aim 2 we will develop
injectable and photo-curable hydrogels synthesized from the natural matrix of dentin and modified with
methacrylates to test the contribution of matrix composition to the regeneration of the pulp vasculature.
Further, we will combine these hydrogels with angiogenic components extracted from the dentin matrix and
test their regenerative potential in vitro and in vivo. In aim 3 we will fabricate architecturally controlled gradients
of ECFC and DPSC paracrine factors using microfluidics techniques to test the contribution of tissue
microarchitecture to the formation of the pulp vasculature. We will then mimic the microarchitectures of
vascularized dental pulp by 3D bioprinting tissue constructs that reproduce the organization of the native pulp.
In the end of this project we expect to have microengineered a 3D vascularized pulp microenvironment that will
improve translational approaches for use in regenerative endodontics in adult teeth.

## Key facts

- **NIH application ID:** 9981727
- **Project number:** 5R01DE026170-05
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Luiz Eduardo Bertassoni
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $503,137
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981727

## Citation

> US National Institutes of Health, RePORTER application 9981727, Microengineering the Dental Pulp Vascular Microenvironment (5R01DE026170-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9981727. Licensed CC0.

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