EVPRO · EVPRO - Development of Extracellular Vesicles loaded hydrogel coatings with immunomodulatory activity for Promoted Regenerative Osseointegration of revision endoprosthesis

Revision endoprosthesis are mostly associated with post-surgical physical symptoms that can lead to long-term confinement to bed and in severe cases to implant rejection. Severe inflammatory reactions in the endoprosthesis shaft can occur due to a previous long-term prosthesis. Medically managing the inflammation process is challenging as it is difficult to introduce drugs to the site of inflammation after implantation of the revision endoprosthesis. EVPRO overcomes this problem by using human mesenchymal stem cell derived extracellular vesicles (MSC-EVs) which are known to suppress inflammatory reaction in humans, exert pro-regenerative effects in osteogenic setting and successfully treat patients with steroid-refractory graft-versus-host disease. In this project the MSC-EVs will be applied in direct physical proximity to the site of inflammation and will therefore affix on the implant surface to deliver their anti-inflammatory and regenerative effect in response to the local inflammation status. This will be achieved by safe integration of the MSC-EVs in a smart biodegradable hydrogel that is absorbed into the micropores of a TiO2 coating on the surface of conventional titan endoprosthesis. EVPRO enables the progression of each individual technology, along with EVPRO system level integration developments, into pre-clinical trials, this means in detail, the development of a GMP conformed large scale production of MSC-EVs, the establishing of an uniform method to purify and select the most potential MSC-EVs with a microfluidic system and the design of a self-regulated hydrogel as protection matrix of MSC-EVs with the function to store and release MSC-EVs in response to the inflammation status, The EVPRO project is an integration of multidisciplinary post-proof of concept technologies which enables the successful resolution of the enhanced osseointegration of endoprosthesis for osteoarticular tissue regeneration.