# Engineered Viscoelastic Hydrogels for Optimized Generation and Transplantation of Human iPSC-Derived Salivary Gland Organoids to Treat Hyposalivation

> **NIH NIH K99** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $115,992

## Abstract

PROJECT SUMMARY
Human salivary gland organoid (SGO) are promising in vitro models for drug discovery, disease modeling,
regenerative therapy. However, the vast majority of organoid derivation protocols rely on ill-defined Matrigel with
tumorigenic origin and immunogenic risks, preventing their translational applications. The dependence of
organoid assembly on self-organization capacity of pluripotent stem cells is another major limitation, leading to
heterogeneous organoids due to stochastic self-assembly. Shifting SGO derivations from stochastic to
deterministic remains a challenge due to lack of information on the regulatory factors dictating pluripotent stem
cells fate during early embryonic development. Such cues – arise from complex cell-cell and cell-extracellular
matrix (ECM) interactions – change spatially and temporally during developmental stages to guide
stem/progenitor cells differentiation, self-organization, and tissue morphogenesis, making in vitro recapitulation
using engineered synthetic matrices is difficult. Indeed, salivary gland embryonic development is a highly
regulated multistage process, starting from pluripotent embryonic precursors, to germ-layer specification, then
to lineage-restricted proximal and distal epithelial progenitors, which specializes to form epithelial compartments
of ductal and acinar cells. Here, we propose development of human induced pluripotent stem cell (iPSC)-derived
SGO with secretory function and well-defined architecture, and revealing the regulatory factors affecting salivary
gland epithelial progenitor (SGEP) colony growth, differentiation, and branching morphogenesis. To achieve this
goal, programmable differentiation of human iPSCs into SGEPs will be conducted. Afterwards, engineered
dynamic hydrogels with fine-tuned physicochemical and biological properties will be utilized to probe the SGEPs
colony response to matrix stiffness, stress-relaxation, degradability, and bioactivity (Aim 1). The information will
be used in a feedback loop to optimize the hydrogel properties for generation of functional SGO, and thus
avoiding the immunogenic risk of the commonly used Matrigel. Furthermore, photoactive hydrogel will be
employed to enable on-demand modulation of matrix mechanics, to enable colony expansion at early stage and
controlled symmetry breaking (onset of morphogenesis) at later stage, thereby generating reproducible SGO for
translational applications (Aim 2). Finally, the secretory function of the SGO will be validated in a preclinical
mouse model of hyposalivation (Aim 3). Overall, the proposed project marks as a conceptual advance in
development of SGO using innovative viscoelastic matrices.

## Key facts

- **NIH application ID:** 10949636
- **Project number:** 1K99DE034072-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Mohamed Alaa Eldein Mohamed
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $115,992
- **Award type:** 1
- **Project period:** 2024-09-06 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10949636

## Citation

> US National Institutes of Health, RePORTER application 10949636, Engineered Viscoelastic Hydrogels for Optimized Generation and Transplantation of Human iPSC-Derived Salivary Gland Organoids to Treat Hyposalivation (1K99DE034072-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10949636. Licensed CC0.

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