by University of Galway

Piezobioreactor Multi-Resonant Configuration for Tunable Piezoelectric Performance and Frequency Selectivity of Mechanically Actuated Acoustic Diaphragm. Schematic representation of tympanic membrane function . Credit: Advanced Science (2024). DOI: 10.1002/advs.202405711

A new study by researchers at the University of Galway and the University of Limerick suggests that electrical stimulation might be essential for tendons to maintain their health, offering fresh possibilities in tendon repair and regeneration.

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Tendons resist intense mechanical stress, while facilitating force transmission from muscles to bones. They are also piezoelectric, meaning that when they are stretched, they will produce an electric field, which is thought to be important for regulating tendon cell function. However, when injured, tendons offer limited healing, which often leads to chronic pain and disability, thus affecting patient productivity.

In 2023, major tears or traumatic injuries to tendon, ligaments and muscles affected nearly half a million people in full-time employment in the United States.

Recovery from tendon injuries is slow and often requires extensive rehabilitation, which causes nearly two months of lost work-days per injury. Current regenerative medicine for tendon repair has so far failed to recreate tendon cells’ native environment, which ultimately hampers their therapeutic potential.

Led by Dr. Marc Fernandez-Yague, who completed his Ph.D. while a researcher with CÚRAM at University of Galway, the research team focused on understanding how electrical and mechanical signals work together to control tendon cell function. Traditionally, tendon cells are extremely difficult to culture in the lab as they rapidly and irreversibly lose their tendon-like functions once isolated from the body.

To address these challenges, the team developed a novel cell culture device—a “tympanic piezoelectric bioreactor” that works in a similar way to the human eardrum and which delivered mechanical vibrations and electrical stimuli to tendon cells. The paper is published in the journal Advanced Science.

Fabrication of a Piezoelectrically Tunable PVDF-TrFE Nanocomposite Membrane. Credit: Advanced Science (2024). DOI: 10.1002/advs.202405711

This dual stimulation caused cells to better retain their healthy, tendon-specific properties, while being expanded in the lab, allowing them to be utilized in tissue repair and regeneration approaches.

Dr. Fernandez-Yague said, “Our work is rooted in a deep understanding of how cells sense and interact with their environment. Until now, tendon cells have been grown in the lab in a specialized device which stretches them to mimic the effects of body movement. However, this approach overlooks that tendon tissues are piezoelectric—they generate electrical signals when subjected to mechanical stress.

“Our research project engineered a dynamic electrical-mechanical stimulation systems, which provides cells with the specific signals they need to successfully guide their development, thereby recreating key environmental conditions observed during normal tissue formation and repair.”

Dr. Manus Biggs, Associate Professor at University of Galway and principal investigator of the study, outlined some wider implications of the research, “While our approach shows great potential for ultimately growing tendon tissues in the lab, it also has significant implications for generating other tissues that respond to dual electrical and mechanical forces, such as cartilage, bone, and even cardiovascular tissues. This study opens up new possibilities for developing therapies that promote tissue reinforcement and offer alternative or complementary strategies to current physical rehabilitation methods.

“We understand that traditional musculoskeletal therapies often rely on physical therapy which provides mechanical signals to the cells of regenerating tissues. In contrast, incorporating electrical stimulation provides greater precision in controlling how cells respond, offering a more effective approaches for applications in regenerative medicine.

“Critically, tendon piezoelectricity has long been alluded to have physiological functions. This study is one of the first of its kind that shows that piezoelectric signals can regulate cell differentiation and development.”

More information: Marc A. Fernandez‐Yague et al, A Tympanic Piezo‐Bioreactor Modulates Ion Channel‐Associated Mechanosignaling to Stabilize Phenotype and Promote Tenogenesis in Human Tendon‐Derived Cells., Advanced Science (2024). DOI: 10.1002/advs.202405711

Journal information:Advanced Science

Provided by University of Galway

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