The coatings developed at EVPRO will be localized at the interface between the implant and the inflamed tissue so that it will perceive inflammation and modulate it in a proportional self-regulated manner, by instructing osteoblasts to migrate into the coating and substitute it by extracellular matrix being the ultimate goal to achieve an improved osseointegration. The proposed research and development will set a new paradigm for bioinstructive coatings for implants with the following functions: mechanical interlocking of implant surface to bone, modulation of local inflammation in a self-adaptive manner and promotion of osseointegration.
EVPRO intend to develop coatings that exploit the anti-inflammatory and immunomodulating properties of mesenchymal-stem-cell-derived extracellular vesicles (MSC-EVs) to locally minimize inflammation. MSC-EVs are vesicles which have been recently recognized as fundamental components of distant and local inter-cellular communication and are able to promote comparable therapeutic activities as MSCs.
The coating will consist of a hard, non-degradable zone (roughened TiO2 surface with graded porosity in the range of macro- to nanopores) and a soft, degradable one; a hydrogel homing MSC-EVs to modulate inflammation. To achieve efficient and localized delivery at the inflammation site, MSC-EVs will be entrapped into a hydrogel coating that provides anchoring and protection of the EVs.
The hydrogel needs to be engineered so that it can detect the presence of inflammation markers and release EVs in a proportional manner and guide the colonization of osteoblast allowing their way towards the implant by degrading. This will be achieved using macromolecular building blocks cross-linked by peptides degradable by matrix metalloproteinases (MMPs), which are overexpressed during inflammation. Such provisional matrix will have biochemical cues instructing colonization by osteoblasts and it will slowly degrade guiding the formation of de novo bone tissue.
Stryker established a unique titanium alloy 3D printing technique to apply a macroporous coating called Tritanium®, mimic cancellous bone structure. Macrophage reactions to debris are responsible for mediating debris-induced inflammation. Plasma electrolytic oxidation (PEO) provides a low-cost modification of surface composition, microstructure and topography producing a hard, wear-resistant, surface finish. EVPRO will apply to a novel 3D-printed Tritanium coating a TiO2 micro porous PEO coating to generate graded micro-to-nanoroughness to the hard part of the endoprosthesis. The newly generated bone will grow in between the spaces provided and this will result in mechanical interlocking thus providing a more stable integration.
The dissemination strategy of EVPRO aims to ensure a high visibility, accessibility and promotion of the project during the grant period.
By addressing all different kinds of stakeholder, EVPRO ensures an effective dissemination. EVPRO uses a project website and other supporting materials like. Among other publications, EVPRO will hold an Open Industrial Day to ensure the dissemination of project results to relevant industries.
