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ENGINEERING CELLULAR SELF‐ORGANISATION BY CONTROLLING THE IMMUNO-MECHANICAL INTERPLAY

Project description

Healing without scarring

Tissue repair after injury is a complex process that involves the interplay between different cell populations and the extracellular matrix. However, repair may not be complete and may lead to scar formation. Bones constitute an exception to this possibility and have an inherent capacity to fully restore their form and function. Funded by the European Research Council, the Immuno-mechanics project aims to investigate the role of the mechanical conditions and stress immune cells encounter after injury. The research also involves the development of artificial niches to study the interactions of immune cells with resident fibroblasts.

Objective

Both scar formation and restitutio ad integrum during bone regeneration rely on cellular self-organisation that involve cell contraction and fibronectin/collagen formation. This early stage of cellular self-organization is later followed by angiogenesis and mineralisation. Scar-free regeneration of physiological tissue homeostasis requires balanced downregulation of early inflammation, however little is understood of the immune-mechanical coupling involved. We aim to lay the foundation for reducing patient suffering resulting from scarring by combining two distinct scientific worlds, for which we have been a major driving force: the distinct regulation of local inflammation and the mechano-biology during regeneration. By combining both of our areas of expertise, we aim to harvest the potential of the novel cross-disciplinary field Immuno-Mechanics.
This ambitious project concentrates first on identifing the different mechanical niches that immune cells experience early in successful healing and non-healing. Second, we will engineer synthetic niches to control fibroblasts and fibroblast-immune cell interactions to steer cell self-organisation and matrix formation in vitro. Third, we plan to verify that these synthetic niches reprogram hematoma composition and can thus reduce later scarring in vivo.
The proposed experiments are challenging as they have never been done this way before, but are feasible since they capitalise on our strengths in osteo-immunology and mechano-biology. Novel technologies will be combined in a unique way to engineer the immune-mechanical cell niche, to passivate activated immune cells and to reprogramme cell fate. This will allow us to substantially advance the basic understanding of the interplay between immune cells and their mechanical niche during early regeneration. By harnessing the mechanisms of the immune-mechanics interplay, we will lay the foundation for advancing immune-modulatory therapies to reduce harmful scarring.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2021-ADG

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Host institution

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
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.

€ 2 490 725,00
Address
Chariteplatz 1
10117 Berlin
Germany

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Region
Berlin Berlin Berlin
Activity type
Higher or Secondary Education Establishments
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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.

€ 2 490 725,00

Beneficiaries (1)

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