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ChondroCONNECT SIGNED

Development of a connexon-proteoliposome delivery system to ameliorate inflammatory and mechanical stress responses in the regeneration of osteoarthritic cartilage

Total Cost €

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EC-Contrib. €

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Partnership

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 ChondroCONNECT project word cloud

Explore the words cloud of the ChondroCONNECT project. It provides you a very rough idea of what is the project "ChondroCONNECT" about.

cells    regenerative    pls    questions    acid    metabolite    surgeons    supplementing    small    stimuli    perform    complementary    rcsi    repair    fellowship    bioactive    abundant    mechanistic    mechanism    collagen    shifts    rna    skills    responsive    screens    clear    escape    cartilage    mechanical    encapsulate    sirna    proteoliposomes    junction    culture    prof    gene    me    protein    college    incorporate    gap    therapeutic    knockdown    engineered    healthy    chondrocytes    disease    metabolism    containing    inflammation    restore    molecules    senescence    promise    endosome    cues    refine    independence    regenerate    cx43    scaffold    roles    interfering    efficacy    training    si    expedite    osteoarthritis    shown    vitro    hyaluronic    proinflammatory    untargeted    connexin    bypasses    expression    phenotypes    therapy    scaffolds    ireland    strategies    connexons    oa    situ    linked    limiting    upregulated    cx    pl    metabolomics    medicine    exceptional    signalling    cell    chondrocyte    platform    environment    metabolic    royal    degenerative    brien    regulation   

Project "ChondroCONNECT" data sheet

The following table provides information about the project.

Coordinator
ROYAL COLLEGE OF SURGEONS IN IRELAND 

Organization address
address: Saint Stephen's Green 123
city: DUBLIN
postcode: 2
website: www.rcsi.ie

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Ireland [IE]
 Total cost 196˙590 €
 EC max contribution 196˙590 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2019
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2020
 Duration (year-month-day) from 2020-07-01   to  2022-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ROYAL COLLEGE OF SURGEONS IN IRELAND IE (DUBLIN) coordinator 196˙590.00

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 Project objective

Regenerative medicine strategies using engineered scaffolds have shown promise to regenerate cartilage in degenerative conditions (e.g. osteoarthritis, OA). However, it is clear further cues are required to control repair in situ. Small interfering (si)RNA can control protein expression but current cell delivery methods require endosome escape, limiting efficacy. Cell delivery of small molecules through connexons (Cx) bypasses the endosome and can be achieved by gap junction formation between cells and engineered Cx-containing proteoliposomes (Cx-PL). The most abundant connexin (Cx43) in cartilage cells (chondrocytes) is also a promising OA therapeutic target. It is highly upregulated in OA and is linked to inflammation, senescence, metabolic shifts and gene regulation. However, many questions remain on its mechanistic role in the disease. This project focuses on Cx43 as a therapeutic target and a delivery mechanism and aims to i) Investigate Cx43 roles in response to OA-associated proinflammatory and mechanical stimuli ii) Develop a Cx-PL delivery platform to knockdown Cx43 and restore healthy metabolism in OA. To study this I will assess chondrocyte responses to proinflammatory and mechanical signalling while controlling Cx43 expression and activity in culture. Using untargeted metabolomics, I will identify key responsive metabolic pathways and perform in vitro screens of the effects of supplementing these to promote healthy phenotypes. Finally, I will encapsulate Cx43-siRNA and a selected bioactive metabolite in Cx43-PLs, incorporate these into a collagen I-hyaluronic acid scaffold and test this delivery platform in vitro. This fellowship conducted with Prof. O’Brien at the Royal College of Surgeons in Ireland will enable me to build on my existing skills in two emerging fields- siRNA therapy and PL-delivery, while the exceptional training environment at RCSI will allow me to refine complementary skills that will expedite my research independence.

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The information about "CHONDROCONNECT" are provided by the European Opendata Portal: CORDIS opendata.

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