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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.

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

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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