Organs-on-Chips (Part 2)

(By Dr. Joseph D. Lim and Dr. Kenneth Lester Lim, BS-MMG, DDM, MSc-OI)

DANIELLE Benoit, PhD and her colleagues, Lisa DeLouise, PhD, and Catherine Ovitt, PhD, are researchers at the University of Rochester.

Founded in 1850, the private research university in Rochester, New York, is one of the world’s leading research universities.

There, Dr. Benoit and her colleagues are developing salivary gland chips for testing drugs that could protect glands from the side effects of radiation therapy for head and neck cancers.

“These chips are valuable as a new tool for probing salivary gland function in vitro,” says Dr. Benoit.

Her research is supported by the National Institute of Dental and Craniofacial Research (NIDCR), a branch of the U.S. National Institutes of Health (NIH). The NIDCR aims to improve the oral, dental, and craniofacial health through research and the distribution of important health information.

The NIDCR is part of the trans-NIH Tissue Chip for Drug Screening program led by the National Center for Advancing Translational Sciences (NCATS). NCATS aims to develop tissue chips to accelerate the translation of basic discoveries into the clinic.

Dr. Benoit’s study is significant because head and neck cancer patients often undergo radiation therapy. During treatment they may experience permanent damage to salivary glands, interfering with saliva production and causing chronic dry mouth.

People need saliva to prevent difficulty in eating and speaking. Without salive, people may be at increased risk for tooth decay and other oral health problems.

A protective drug called amifostine are often prescribed before radiotherapy. However, the side effect is a dramatic drop in blood pressure. This has prevented many clinicians to prescribe the drug, depriving many patients of its preventive use.

To find better radioprotective drugs, Dr. Benoit and her research team at Rochester developed a tissue chip that holds hundreds of tiny, human salivary gland-like cell clusters. The do this to perform rapid drug screening.

Each salivary gland cell cluster is suspended in a gel-like material. The cell cluster is then seeded into a fishbowl-shaped microbubble that’s smaller than a grain of sand.

The unique shape of the sand-like bubbles clusters resembles real salivary glands. The tiny grain-sized bubbles also concentrate proteins and molecules to keep the tissue alive and functioning.

In a study published in 2021 in the Communications Biology scientific journal, Dr. Benoit and her colleagues reported that the salivary gland clusters maintained cell organization, expressed genes, secreted proteins, and responded to fluid-secretion signals much like real salivary glands.

The study found that the drug amifostine protected the cell clusters from radiation-induced damage, indicating the potential for salivary gland chips to facilitate large-scale drug studies.

Dr. Benoit and her research team now plans to screen more than 800 compounds approved by the U.S. Food and Drug Administration to find radioprotective drugs that might be repurposed for head and neck cancer patients.

Elsewhere, other research teams supported by the NIDCR continue their studies using organ-on-chips technology such as developing mouth-related chips.

Some research groups are crafting chips that mimic oral barrier tissue to understand gum disease. Other scientists are engineering a gum-tissue chip to develop treatments for mouth sores caused by cancer therapy.

Still another research team is even building a “human”-on-a-chip by integrating tissue from multiple body systems. The project is supported by NIDCR and several other NIH institutes as part of the trans-NIH tissue chip program.

“These chips really have translational potential for discovering something that could impact patient care,” says Dr. Lisa DeLouise, Dr. Benoit’s colleague at the University of Rochester. “That motivates me, and that’s why I’m excited.”

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Dr. Joseph D. Lim is the former Associate Dean of the College of Dentistry, University of the East; former Dean, College of Dentistry, National University; Past President and Honorary Fellow of the Asian Oral Implant Academy; Honorary Fellow of the Japan College of Oral Implantologists; and Honorary Life Member of the Thai Association of Dental Implantology. For questions on dental health, e-mail jdlim2008@gmail.com or text 0917-8591515.

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Dr. Kenneth Lester Lim, BS-MMG, DDM, MSc-OI, graduated Doctor of Dental Medicine, University of the Philippines College of Dentistry, Manila, 2011; Bachelor of Science in Marketing Management, De la Salle University, Manila, 2002; and Master of Science (MSc.) in Oral Implantology, Goethe University, Frankfurt, Germany, 2019. He is an Associate professor; Fellow, International Congress of Oral Implantologists; Member, American Academy of Implant Dentistry and Philippine College of Oral Implantologists. For questions on dental health, e-mail limdentalcenter@gmail.com/PN

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