Millions suffer from xerostomia, or dry mouth—a painful condition often caused by cancer treatments or autoimmune disease. Now, scientists have developed a smart hydrogel system that mimics the native salivary gland environment, enabling human salivary cells to grow and function in three-dimensional (3D) spheroids. Built from a blend of hyaluronic acid, alginate, and gelatin, the matrix supports the expansion and organization of acinar cells, the key fluid-producing units of the gland. These lab-grown spheroids not only remain viable and structurally intact over two weeks but also demonstrate real functional activity, responding to biochemical signals much like their natural counterparts. The innovation marks a leap forward in tissue modeling and potential regenerative therapies.
Salivary glands play an essential role in protecting oral health by secreting saliva to aid in digestion, speech, and immunity. When these glands are irreversibly damaged—by radiotherapy or autoimmune attacks—patients often face chronic discomfort, difficulty eating, and increased risk of infection. Yet recreating salivary function in the lab remains an elusive challenge due to the complexity of the gland's specialized cells and microenvironment. Most existing culture systems rely on animal-derived scaffolds or chemically fixed matrices that fail to sustain human acinar cell identity over time. Due to these limitations, there is a pressing need for bioengineered three-dimensional (3D) environments that support long-term survival and function of salivary gland cells.
In a new study (DOI: 10.1038/s41368-025-00368-6) published on May 9, 2025, in the International Journal of Oral Science , researchers from McGill University unveiled a next-generation hydrogel that supports the regeneration of salivary gland-like tissue. The team tested three formulations and found that the version containing hyaluronic acid—referred to as AGHA—best supported the formation of large, viable spheroids that mimic native gland architecture. These 3D cell clusters maintained high expression of key salivary proteins and responded dynamically to chemical stimulation, offering a powerful tool for modeling diseases and testing potential therapies for xerostomia.
The researchers compared three hydrogel types: a basic alginate–gelatin (AG), a collagen-supplemented version (AGC), and hyaluronic acid-containing AG (AGHA), which incorporates hyaluronic acid. While all demonstrated mechanical properties similar to native tissue, AGHA emerged as the superior scaffold. In AGHA gels, salivary acinar cells formed large spheroids containing more than 100 cells with over 93% viability. These structures maintained metabolic activity and robust expression of functional markers including AQP5 , ZO-1, NKCC1, and α-amylase —all essential for saliva secretion. When stimulated with isoprenaline, the spheroids increased their production of α-amylase-containing granules, confirming their functional responsiveness. The gel's reversibility, achieved through simple ion removal, allowed for non-destructive retrieval of intact spheroids—an essential feature for downstream clinical or experimental use. The hydrogel also successfully supported the expansion of primary human salivary cells for up to 15 days, demonstrating its versatility as a culture platform.
"This study demonstrates that by fine-tuning hydrogel composition, we can closely replicate the native environment of salivary acinar cells," said Dr. Simon D. Tran, senior author of the study. "Our AGHA-based platform not only supports long-term viability and function, but also enables easy recovery of spheroids without enzymatic damage. This is a significant step forward in developing in vitro models for salivary gland disorders and potential regenerative therapies for patients suffering from chronic dry mouth."
The implications of this hydrogel system extend beyond xerostomia. By enabling the growth of functional salivary tissue in a lab-friendly, reversible matrix, this platform could accelerate the development of disease models, high-throughput drug screening tools, and even implantable grafts. Its compatibility with both immortalized cell lines and primary human cells makes it a versatile foundation for future regenerative applications. Moreover, eliminating animal-derived materials improves reproducibility and clinical relevance. With this innovation, researchers are one step closer to restoring natural salivary function for patients who need it most.
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References
DOI
Original Source URL
https://doi.org/10.1038/s41368-025-00368-6
Funding information
This work was supported by the financial support from Fonds de Recherche du Québec Santé (FRQS, grant no. 281271).
About International Journal of Oral Science
International Journal of Oral Science (ISSN 1674-2818) was founded in 2009 and aims to publish all aspects of oral science and interdisciplinary fields, including fundamental, applied and clinical research. Covered areas include oral microbiology, oral and maxillofacial oncology, cariology, oral inflammation and infection, dental stem cells and regenerative medicine, craniofacial surgery, dental materials, oral biomechanics, oral, dental and maxillofacial genetic and developmental diseases.
International Journal of Oral Science
Not applicable
Expansion of functional human salivary acinar cell spheroids with reversible thermo-ionically crosslinked 3D hydrogels
9-May-2025
The authors declare that they have no competing interests.