# Directing Collective Epithelial Morphology in Space and Time Using a Light-Based Carving Tool

> **NIH NIH R03** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $155,666

## Abstract

Project Summary:
Xerostomia, or “dry mouth”, is a challenging clinical condition, caused by damage to the cells of the salivary
gland. It may result from a variety of tissue insults, including acute damage from radiation therapy for head and
neck cancers, progressive auto-immune response in Sjogren’s disease, or other unknown etiology from aging.
Current treatments offer only temporary relief of symptoms, and poor resolution of associated oral health
decay. The cost of this condition is considerable, both in quality of life and the financial burden of increased
dental care. The fields of tissue engineering and regenerative medicine offer many tools for the potential
reconstitution of healthy salivary-derived cells within supportive hydrogel matrices, but few of these options
provide sufficient spatial and temporal resolution to restore the complex branched structure and precise spatial
phenotype map of the major salivary glands. However, new discoveries in laser-based hydrogel degradation
(LBHD) can be used to “carve” pathways through intact hydrogel slabs, with pinpoint, subcellular resolution in
xyz, and offer a method to guide a growing salivary epithelial bud in 3 dimensions. Our hypothesis for the
present proposal is that we can use multiphoton-based LBHD to elongate a multicellular cluster in a given
direction, and recreate key elements of the native gland. To do this, we will employ our laboratory’s expertise in
isolation of primary human salivary-derived stem/progenitor cells (hS/PCs) from healthy tissues, and
encapsulation as responsive 3D multicellular spheroid clusters within customizable, biocompatible hyaluronic
acid (HA) hydrogels. Our ongoing work has shown that, by tailoring the porosity of these hydrogels and their
concentration of bioactive epitopes, we can impact cluster size, morphology, and interaction with the
surrounding extracellular matrix. We will test our hypothesis through the following Specific Aims:
Aim 1. Establish parameters to carve “tunnels” through HA hydrogels and promote HS/PC cluster ingrowth.
Aim 2. Adapt the system to alternate matrices that enable fibroblast co-culture, or incorporate photolabile
crosslinkers for easier fabrication. Aim 3. Assess phenotype of the growing cluster, at its trailing and leading
edges and branched termini, for signs of differentiated phenotype. If successful, this system could serve as a
useful model for studying mechanisms of human salivary cell organization and differentiation; the system might
also be an early prototype for manufacturing tissue engineered gland replacements. The R03 mechanism will
provide support for the necessary pilot and feasibility studies, to demonstrate that these proven technologies
can be combined to produce a novel platform.

## Key facts

- **NIH application ID:** 9968401
- **Project number:** 5R03DE028988-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Daniel A Harrington
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,666
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968401

## Citation

> US National Institutes of Health, RePORTER application 9968401, Directing Collective Epithelial Morphology in Space and Time Using a Light-Based Carving Tool (5R03DE028988-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9968401. Licensed CC0.

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