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Local Immunomodulation around implants by innovative auxiliary hydrogel-based systems encapsulating autologous and phenotype controlled macrophages (IMMODGEL)
Date du début: 1 oct. 2013, Date de fin: 30 sept. 2017 PROJET  TERMINÉ 

IMMODGEL aims to identify adverse immune reactions to dental and larynx titanium implants and to develop a novel therapeutic strategy to significantly decrease the implant and medical device failure caused by these reactions via design of an innovative immunomodulatory system. The system will be designed to be fixed to an implant via an adhesive polyelectrolyte multilayer and control the immune response by autologous, phenotype modulated macrophages encapsulated in a hydrogel. The auxiliary nature of the design allows it to be adjusted to any implant, medical device or transplant. IMMODGEL will apply complex systems immunology, epidemiology, and functional approaches to identify key adverse immune reactions caused by implants and detrimental macrophage phenotypes around titanium implants. This will be used to establish the optimal biomaterial composition and cytokine delivery system for the immunomodulatory hydrogel design to revert macrophage-induced inflammatory reactions (M1) to the optimal tolerogenic and healing reactions (M2). Long-term fixation of the desired M2 phenotype will significantly decrease the level and duration of implant-induced inflammation, and optimise healing phase. The interaction of implants and medical devices with the immune system will be modelled to develop a “Foreign Body Response on-a-chip” to predict patient’s specific responses to implant materials and modify the immunomodulatory hydrogel accordingly, as a step towards personalized implants with minimal adverse reactions. The gels will be incorporated to engineered tissues for validation. Validation of the approach will be performed in vivo in animal models. Significantly suppressed inflammatory responses and optimal tissue remodelling and healing around titanium implants is expected. The key innovation will be the development of IMMODGEL as an auxiliary system to improve the outcomes of implantation and reduce the cost of implant complication and related medical costs in Europe.

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