# Engineered 3D Periodontal Tissue Constructs for Defining Functional Outcomes of Regenerative Processes

> **NIH NIH R03** · UNIVERSITY OF WASHINGTON · 2021 · $176,500

## Abstract

Project Summary. Knowledge of the effects of inflammation on the regenerative functions of
periodontal ligament (PDL) cells is incomplete. This limits the development of techniques for
periodontal regeneration that will maintain functional tooth support over the long term.
Periodontal regeneration includes multiple cellular processes and a less understood component
of these processes is PDL cell contractility. Cellular contractile forces are critical to the
alignment of collagen fibrils that strengthen periodontal tissue and maintain its functional
integrity. The long-term goal of this research is to identify mechanisms regulating PDL cell
mechanics that can be used as clinical tools for regenerating and maintaining the architecture
and function of the periodontal complex over time. Thus, the objective of this proposal is to
demonstrate links between mechanisms regulating PDL cell contractile forces in
proinflammatory microenvironments with PDL architecture and tissue mechanics. The central
hypothesis of this proposal is that the inflammatory microenvironment regulates PDL cell
contractile forces with effects on PDL tissue architecture and mechanics. This hypothesis will be
tested in Specific Aim 1 through identification of mechanisms that regulate in vitro PDL cell
contractile forces within proinflammatory microenvironments at the single-cell level. Western
blots will be used to determine effects of tumor necrosis factor alpha (TNF) and hyaluronan
oligosaccharide (oHA) on signaling pathways that generate cellular contractile force, such as
the Rho/Rock pathway. In order to link the inflammatory environment and cell signaling with
contractility, cellular traction forces will be measured with and without inflammatory mediators
and signaling pathway inhibitors. In Specific Aim 2, three-dimensional PDL constructs will be
developed to link the signaling pathways that regulate tissue-level contractility with matrix
architecture and stiffness. Engineered PDL constructs will be developed using PDL cells and
collagen and in situ forces will be measured. PDL constructs will be treated with stimulants and
inhibitors of the Rho/Rock pathway under conditions that model periodontal homeostasis and
inflammation. The successful completion of these aims will contribute to the development of
clinical techniques for maintaining the PDL or regenerated tissues in a proinflammatory
environment. Future research will expand this model to include cementum-like tissue and bone;
thus, this pilot study is an initial step toward the future goal of regenerating the periodontal
complex and maintaining its functional integrity over the long-term.

## Key facts

- **NIH application ID:** 10189554
- **Project number:** 5R03DE029827-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** TRACY E POPOWICS
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $176,500
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189554

## Citation

> US National Institutes of Health, RePORTER application 10189554, Engineered 3D Periodontal Tissue Constructs for Defining Functional Outcomes of Regenerative Processes (5R03DE029827-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10189554. Licensed CC0.

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