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Gating cell force sensors with tailor-made nanoswitches to restore tendon tissue function

Project description

Mechano-biology, molecular imprinting and magnetic systems for tendon repair

Understanding tendon mechano-biology is vital for developing effective treatments. PIEZO channels play a key role in how tendons sense and adapt to mechanical loading. The main challenge is effectively targeting these sensors in tendon cells, as well as understanding the biological feedback from their activation. The ERC-funded FORTIFy project will create a wireless platform of customised nanoswitches to manipulate PIEZO receptors by integrating molecular imprinting technologies with magnetic systems. Utilising advanced humanised 3D microphysiological systems, it will investigate tendon microenvironments to enhance bioengineered tendon grafts. It will focus on the role of PIEZO-mediated mechano-signalling in tendon health and degeneration, emphasising neurotendinous interactions and their immunomodulatory effects. Successful outcomes could lead to novel nanomedicine tools for treating tendinopathy.

Objective

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.

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Call for proposal

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(opens in new window) ERC-2024-COG

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Host institution

INTERNATIONAL IBERIAN NANOTECHNOLOGY LABORATORY
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 999 186,00
Address
AVENIDA MESTRE JOSE VEIGA
4715-330 Braga
Portugal

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Region
Continente Norte Cávado
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 999 186,00

Beneficiaries (1)

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