# THE USE OF FIBRIN HYDROGELS TO PROMOTE SALIVARY GLAND REGENERATION

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $394,480

## Abstract

ABSTRACT
 Our work to date on the current grant has yielded the following results: a) single mouse parotid cells were
found to form three-dimensional (3D) cell clusters displaying TJ and agonist-induced secretory responses
when grown on Growth Factor-Reduced Matrigel (GFR-MG) in combination with Fibrin Hydrogel1 (FH), b) the
ratio of GRF-MG and FH was optimized with the ultimate goal of creating a functional and clinically safe
scaffold1, c) our salivary cell isolation method was improved to maintain secretory granules, form TJ and
facilitate cell survival, d) mouse submandibular gland (mSMG) cells, rather than parotid or sublingual glands,
were found to be the best choice for creating salivary cell clusters displaying organized morphology, e) critical
components were identified within GFR-MG (i.e., EGF and IGF-1) that enhance salivary gland (SG)
differentiation when polymerized to FH, f) EGF and IGF-1 were found to be incapable of independently
producing organized cell clusters; however, this goal was achieved using Laminin-1 (L1), g) peptides
(corresponding to four L1 regions that promote intact SG formation) were synthesized and conjugated to FH, h)
specific L1 peptides induced formation of acinar spheres in the rat parotid cell line Par-C10 (as compared to
cells grown on FH alone), i) addition of a conditioned medium from human hair follicle mesenchymal stem cells
(hHF-MSC CM) improved salivary cell cluster organization and lumen formation in mSMG cells, j) salivary cell
clusters maintained acinar, ductal and myoepithelial cells while responding to secretory agonists, k) lumen
formation was impeded with the blocking of FGF10 in hHF-MSC CM, l) high amounts of FGF2 were detected in
a hHF-MSC CM in which intact salivary cell clusters were grown, m) L1 peptides chemically conjugated to
fluorescent FH were applied to wounded mSMG in vivo to form new salivary tissue, as compared to FH alone
or no scaffold, and mice were healthy after the treatment. Taken as a whole, the above studies indicate we
have accomplished the majority of our initial goals during the first three years of this grant and found viable
alternatives for the difficulties encountered (e.g., use of L1 peptides to enhance FH and improve salivary cell
clusters formation, as noted above). In the coming grant period, we will refine our design for a clinically safe
environment as follows: a) produce a FH modified with L1 peptides and growth factors, b) grow differentiated
salivary cell clusters in these matrices and c) use modified FH scaffold to form new and functional tissue in vivo
(with aim of later applying these findings to humans with SG dysfunction due to Sjögren's syndrome as well as
head and neck γ-irradiation treatments).

## Key facts

- **NIH application ID:** 10232515
- **Project number:** 7R01DE022971-10
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Stelios T. Andreadis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $394,480
- **Award type:** 7
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232515

## Citation

> US National Institutes of Health, RePORTER application 10232515, THE USE OF FIBRIN HYDROGELS TO PROMOTE SALIVARY GLAND REGENERATION (7R01DE022971-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10232515. Licensed CC0.

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