Christopher Raub, Ph.D., associate professor and chair of the Department of Biomedical Engineering, received a grant from the National Institute of Dental and Craniofacial Research (NIDCR) of the National Institutes of Health (NIH) for his project, “Determining Molecular Mechanisms of Damage and Repair in an Oral Mucosa Chip.” The grant is a 2-year R03 award with total direct costs of $200,000. This funding will support continued collaboration between Raub and mechanical engineering colleague Xiaolong Luo, Ph.D., whose combined research efforts have led to the development of an oral mucosa chip and the model of chemoradiation-induced mucositis.

Raub and his team of biomedical and mechanical engineers at The Catholic University of America spent the last seven years developing a robust, reproducible oral mucosa tissue chip, for understanding how agents damage human mucosal tissues and also potential protective, therapeutic, and prophylactic treatments against mucosal damage.

The tissue chip is a small piece of glass and plastic that can be held in the hand, containing microscale channels filled with living cells and nutrient-rich fluid, and that recapitulates aspects of normal and pathophysiological human tissue functions. They are envisioned to be able to accurately predict human tissue responses to damage, repair, and therapies.

In the context of cancer therapies and exposure to radiation, the oral mucosa (mucous membrane lining the inside of the mouth) often suffers a painful inflammatory condition known as mucositis, and the oral mucosa chip is designed to aid in developing new treatments for this condition. The oral mucositis tissue chip developed by Raub and his team holds promise in the search for safe and effective anti-mucositis therapies. As a simple, inexpensive, yet reliable platform to study cancer-treatment-induced mucositis, it allows researchers to directly observe damage and recovery of the cells in the mucosa-like tissue layers in the chip, using microscopes. New breakthroughs in our understanding and treatment of oral mucositis via this novel technology will help many U.S. citizens, veterans, and people worldwide who suffer from this condition.

The sensitive mucosal tissues of our mouth, nose, and airways are also the primary targets of several chemical warfare agents as well as potential bioengineered aerosolized agents. As a sentinel tissue, the oral mucosa is also easily damaged by toxic and radioactive agents and therefore the chip may be used to evaluate unknown substances for potential health risks. The oral mucosa tissue chip has utility for testing toxic agents associated with chemical and biological warfare, and for evaluating potential prophylactic and post hoc therapeutic agents, without the time and expense of developing animal models and with the added benefit of testing on human cells.

Recently, the team found that recombinant truncated human keratinocyte growth factor (drug name: palifermin) protected the oral mucosa tissue in the chip from damage by cytotoxic and oxidative damage-inducing agents, in a dose-dependent manner. They are currently engineering the tissue chip into a high throughput array, with in-built mechanical stress and other biosensors, and incubating microbes and other pathogens in the mucosa chip, to determine mechanisms of infection and damage. Raub and his team look forward to further developing and applying this technology, to improve our understanding and treatment of mucositis and the oral mucosa more broadly.

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