A Self‐Powered Piezo‐Bioelectric Device Regulates Tendon Repair‐Associated Signaling Pathways through Modulation of Mechanosensitive Ion Channels
Marc A. Fernandez‐Yague, Alexandre Trotier, Seçil Demir, Sunny Akogwu Abbah, Aitor Larrañaga, Arun Thirumaran, Aimee Stapleton, Syed A. M. Tofail, Matteo Palma, Michelle Kilcoyne, Abhay Pandit, Manus Biggs
Abstract
Following injury, disorganized tissue deposition leads to scar tissue formation, proteoglycan accumulation, and calcification, resulting in poor biomechanical properties and impaired function that triggers chronic inflammatory signaling pathways and progresses into tendinopathy. Hence, to achieve long-term repair, innovative functional solutions that focus on the activation of endogenous tissuerepair signaling pathways represents a paradigm shift in the field of biomedical devices and regenerative medicine (RM). 7] Innovative solutions are required to overcome the limitations of current tendon grafting approaches, and bioelectronic therapies show promise in treating musculoskeletal diseases, accelerating functional recovery through the activation of tissue regenerationspecific signaling pathways. Self-powered bioelectronic devices, particularly piezoelectric materials, represent a paradigm shift in biomedicine, negating the need for battery or external powering and complementing existing mechanotherapy to accelerate the repair processes. Here, the dynamic response of tendon cells to a piezoelectric collagen-analogue scaffold comprised of aligned nanoscale fibers made of the ferroelectric material poly(vinylidene fluoride-co-trifluoroethylene) is shown. It is demonstrated that motionpowered electromechanical stimulation of tendon tissue through piezobioelectric device results in ion channel modulation in vitro and regulates specific tissue regeneration signaling pathways. Finally, the potential of the piezo-bioelectronic device in modulating the progression of tendinopathyassociated processes in vivo, using a rat Achilles acute injury model is shown. This study indicates that electromechanical stimulation regulates mechanosensitive ion channel sensitivity and promotes tendon-specific over non-tenogenic tissue repair processes.