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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.

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

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

Map

 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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