Scientists create lab-grown saliva tissue in response to chemical signals

McGill University researchers have developed a new hydrogel system that successfully implants functional salivary gland tissue in the laboratory, offering hope for millions of patients with chronic dry mouth.

The team’s innovative approach uses a special gel that contains hyaluronic acid, which mimics the natural environment where salivary cells flourish and creates three-dimensional structures that behave very much like real salivary glands.

The study, published on May 9, 2025 in the International Journal of Oral Sciences, represents a significant advancement in addressing venemia, a medical term for chronic dry oral surgery that affects patients who undergo radiation therapy for head and neck cancer or autoimmune diseases such as Sjögren syndrome.

A gel that mimics nature

What makes this study particularly compelling is how scientists solve a fundamental challenge: allowing human saliva cells to survive and function in the body. Most existing laboratory systems rely on animal-derived materials or chemically fixed matrices that fail to maintain the professional identity of human acinar cells over time.

The team tested three different gel formulas and finally found that its hyaluronic acid-containing version, called AGHA, produced the most promising results. In these gels, salivary cells spontaneously organize into large spherical clusters, each containing more than 100 cells, with the remaining 93% more.

The structures of these labs growing are notable for their ability to maintain molecular machinery essential for saliva production. These cells continue to express key proteins, including AQP5, ZO-1, NKCC1 and alpha-amylase, all key components of the natural saliva production process.

React like a real tissue

Perhaps most importantly, these artificial saliva structures exhibit functional responsiveness. When researchers expose them to chemicals that usually stimulate saliva production, lab-grown tissue increases the production of its alpha-amylase-containing particles, which actually mimics what happens in your healthy mouth when you smell your favorite food.

“This study shows that by fine-tuning the hydrogel composition, we can closely replicate the local 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 easily restores spheroids without enzymatic damage. This is an important step in developing in vitro models of salivary gland disease and potential regenerative therapies for patients with chronic dry mouth.”

Beyond the laboratory bench

The researchers made an important finding that was not highlighted in the initial announcement: their gel system successfully supported the expansion of primary human salivary cells for up to 15 days. This finding is particularly important because primary cells (taken directly from human tissue rather than immortal cell lines) are difficult to maintain under laboratory conditions but are essential for the development of clinically relevant treatments.

The mechanical properties of these gels are very well matched with the mechanical properties of natural human salivary gland tissue, with a stiffness of about 11 kg. This biomechanical similarity seems crucial to maintaining the natural behavior and tissue patterns of cells.

Key Benefits of New Systems

• Reversible gel matrix allows for lossless intact spherical retrieval
• Eliminates the need for animal-derived materials and improves repeatability
• Cell lines supporting immortality and primary human cells
• Maintain long-term functional protein expression

Clinical significance

These implications go far beyond static therapy. The platform could accelerate the development of disease models, enable high-throughput drug screening, and could lead to implant implant grafts that restore natural saliva function.

For patients currently managing chronic dry mouth with temporary solutions such as saliva stimulating medications or palliative care, this study provides a glimpse of more permanent treatment options. The capacity of functional salivary tissue to respond to natural stimuli represents a critical step in developing regenerative therapy.

The research team used thermal ion crosslinking method to create what they call a “two-phase 3D model”, whose partially crosslinked soft core is surrounded by a fixed shell. This unique structure could explain why gels containing hyaluronic acid are much better performing than alternatives that contain collagen or alkaline alginate wise protein combinations.

expect

Although this represents a significant advance, the researchers acknowledge that fully functional saliva secretion may need to be involved in other cell types other than acinar cells. Future work will focus on the development of co-culture systems to integrate complex cellular structures found in natural salivary glands.

The team’s success in laboratory cell lines and primary human tissues demonstrates that their platform can serve as a multifunctional basis for testing treatments within the scope of salivary gland disease. Through this innovation, researchers have come closer to the millions of patients who need it the most to restore their natural saliva function.