Project description
Mechanistic insight into bone repair
Bone healing after a fracture begins with localised inflammation followed by bone regrowth and remodelling. The process responds to mechanical stimulation, but the underlying molecular mechanisms remain poorly understood. Moreover, this response to mechanical stimulation may decline with age. The EU-funded project, MechanoHealing, will delineate the mechanobiology of bone healing by studying how individual bone cells translate mechanical stimuli into repair. The project will employ a multi-disciplinary approach to profile individual cells, the mechanical environment at the fracture site and the nanostructure of the newly formed bone. Results will lead to a better understanding of the age-associated decline in bone repair and to targeted intervention therapies against cases where healing is delayed or fails.
Objective
Delayed bone healing or failed non-unions account for 5 – 10% of all bone fractures and present a challenging problem in regenerative medicine. Bone healing is a mechano-sensitive process; thus, mechanical stimuli can either enhance or impair fracture healing. The molecular mechanisms underlying this phenomenon are complex and poorly understood. Consequently, clinical applications which harness this mechano-sensitivity to enhance healing are limited. It has also contributed to a lack of consensus on whether bone exhibits age-associated declines in mechano-sensitivity. With this in mind, I present a multi-scale, multi-disciplinary approach to develop a molecular-based understanding of bone healing mechanobiology and to investigate how this mechano-sensitivity is compromised with age. Using an established femur defect model in young and aged mice, my proposed approach will apply state-of-the-art techniques to spatially map: (i) the local mechanical environment, (ii) the molecular profiles of single cells, and (iii) the local tissue nanostructure within the fracture callus. By combining single-cell “omics” technologies with established tissue-scale models of bone mechanobiology, MechanoHealing will quantify how mechanical stimuli are translated by individual cells and subcellular components to form bone. MechanoHealing will also permit investigations into potential pathways by which mechanical stimuli influence formation of the nanostructure of bone – a key determinant of the overall fracture resistance of bone. Identification of the molecular mechanisms of mechanically-driven bone formation will lead to new strategies and novel therapeutic targets to promote better and faster repair. Specifically, it will drive the development of safe, targeted and individualized mechanical intervention therapies. Furthermore, insights into age-associated declines in mechano-sensitivity will better equip surgeons to optimize outcomes in compromised healing environments.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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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.
8092 Zuerich
Switzerland
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.