| Project Detail |
It’s becoming increasingly clear that a deeper understanding of tendon mechanobiology is required for the development of effective therapies for tendon injuries and diseases. The involvement of specialized cell force sensors, such as PIEZO channels, on the mechanosensory processes through which tendons sense and adapt to mechanical loading have just started to be unveiled. Decoding the underlying mechanisms governing these processes would promote the development of innovative therapies to restore tendon function. However, a remaining barrier to unlock the therapeutic potential of PIEZOs is how to effectively target and gate these complex mechanoreceptors in different tendon cell populations (both in vitro and in vivo) and what are the actual biological feedbacks of its activation. FORTFy ground-breaking concept will merge molecularly imprinting technologies and magnetic systems to establish a versatile wireless platform of tailor-made abiotic nanoswitches for the programmed manipulation of PIEZO receptors. Combined with a new generation of advanced tools, including humanized 3D microphysiological systems enabling to study the multicellular crosstalk occurring in tendon microenvironments and to obtain improved bioengineered tendon grafts, it will enable to explore the full potential of PIEZOs as targets for treatment of tendinopathy. The challenging ambition of FORTFy will be accomplished by implementing a thorough in silico, in vitro and in vivo research plan aimed at probing the role of PIEZO-mediated mechanosignaling on tendon homeostasis, degeneration and aging, focusing the neurotendinous crosstalk and its immunomodulatory signatures. The success of FORTFy will not only lead to unprecedented nanomedicine tools for treatment of tendinopathy, but its fundamental concepts will certainly impact the therapeutic options of a wide range of other PIEZO-regulated diseases related with musculoskeletal dysfunctions, immunological responses and proprioception. |
