Periodic Reporting for period 2 - EVPRO (EVPRO - Development of Extracellular Vesicles loaded hydrogel coatings with immunomodulatory activity for Promoted Regenerative Osseointegration of revision endoprosthesis)
Periodo di rendicontazione: 2020-07-01 al 2021-12-31
Hip joint replacement by endoprosthesis is well established and for medium-term timescales, is an “effective” intervention for patients suffering from degenerative joint diseases. The number of total hip replacements has steadily increased in the past ten years and will continue to grow due to the demographic change. Because of the increasing number of primary hip replacements, the number of revision surgeries will increase as well, and while being patient-related it is also a significant economic problem.
Aseptic loosening, which is the induction of an osteolytic cascade due to a chronic inflammatory response, is the main cause of complications and replacement of hip implants. The partners expect that EVPRO's results lead to a significant decrease in aseptic loosening in joint replacement. The postoperative outcome will be improved, resulting in an accelerated full-load mobilisation and enhanced active ageing with more quality of life by diminishing problems associated with implanted joint prosthesis and by reducing the number and frequency of subsequent medical treatments.
The ambition of EVPRO is to set a new paradigm in the design of artificial endoprosthesis towards biohybrid implants. The objective of EVPRO is to devise a novel bioinstructive and adaptive coating for hip revision endoprosthesis able to control inflammation at the original anatomical location of the removed endoprosthesis and promote bone regeneration.
Aseptic loosening, which is the induction of an osteolytic cascade due to a chronic inflammatory response, is the main cause of complications and replacement of hip implants. The partners expect that EVPRO's results lead to a significant decrease in aseptic loosening in joint replacement. The postoperative outcome will be improved, resulting in an accelerated full-load mobilisation and enhanced active ageing with more quality of life by diminishing problems associated with implanted joint prosthesis and by reducing the number and frequency of subsequent medical treatments.
The ambition of EVPRO is to set a new paradigm in the design of artificial endoprosthesis towards biohybrid implants. The objective of EVPRO is to devise a novel bioinstructive and adaptive coating for hip revision endoprosthesis able to control inflammation at the original anatomical location of the removed endoprosthesis and promote bone regeneration.
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.
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.
The EVPRO project is an integration of multidisciplinary post-proof of concept technologies, and will fuse emerging technologies established in the laboratory into a novel approach, advancing each subarea in the direction of industrial production. Combined with versatility of EVs as therapeutics results in a unique and advantageous approach to significantly extend the complication-free interval and to improve the longevity of the EVPRO-derived revision endoprosthesis. The consortium of European universities and part-ners in medical device and biotechnology industries will focus on building a market leading portfolio of products, required for application in the next generation of hip revision endoprosthesis and beyond. As a logical extension for a later stage utilization analysis, further joint replacements such as shoulder, ankle or elbow replacements could also directly benefit from the EVPRO technology. Additionally, clinical areas connected with high inflammation rates for further EV-loaded products represent a promising and broad chance for further exploitation of the EVPRO technology.
The advance of EVPRO represents a vast opportunity for the design and development of future osteo-related medical devices and implants of all kind. Therefore, strategies to foster bone regeneration are intensely sought and translation of this innovation into a practical use product is highly desirable for industry and society. The multidisciplinary network of EVPRO will apply state-of-the-art expertise to develop highly-innovative concepts and prototypes to progress towards next steps in the translation of bioactive (nano) materials and R&D to clinical practice. Overall, EVPRO provides new therapeutic biomaterials for clinical bone implants and joint replacements by excellent options to create new biomedical and technological opportunities. With impact beyond EVPRO, the actions will enable establishing feasible solutions with high market potential for emerging novel MSC-EV-biomaterial technologies that instruct and control tissue (re)generation. EVPRO will also provide a novel platform for future application of MSC-EVs-hydrogel-TiO2 coating to many types of implants.
The advance of EVPRO represents a vast opportunity for the design and development of future osteo-related medical devices and implants of all kind. Therefore, strategies to foster bone regeneration are intensely sought and translation of this innovation into a practical use product is highly desirable for industry and society. The multidisciplinary network of EVPRO will apply state-of-the-art expertise to develop highly-innovative concepts and prototypes to progress towards next steps in the translation of bioactive (nano) materials and R&D to clinical practice. Overall, EVPRO provides new therapeutic biomaterials for clinical bone implants and joint replacements by excellent options to create new biomedical and technological opportunities. With impact beyond EVPRO, the actions will enable establishing feasible solutions with high market potential for emerging novel MSC-EV-biomaterial technologies that instruct and control tissue (re)generation. EVPRO will also provide a novel platform for future application of MSC-EVs-hydrogel-TiO2 coating to many types of implants.