Contact. Protip. Scientific coordinator. Dr. Engin Vrana Steinbeis-Europa-Zentrum

Transcription

1 Newsletter No. 2 Dear Readers, Welcome to the second issue of our Immodgel newsletter! In this edition, we show you Immodgel s relevance in terms of market and customer needs. We also introduce Steinbeis-Europa-Zentrum, administrative coordinator of the project. Last but not least, we present the first review including project related results and inform you on past and upcoming events. We warmly invite you to visit our project website under immodgel as well as our LinkedIn page where you will find updated information on the project and its partners. We hope you will enjoy reading and are looking forward to sharing future news with you in the coming issues. Yours, sincerely, The Immodgel consortium Immodgel in brief Project title Local immunomodulation around implants by innovative hydrogel-based systems Short name Immodgel Funding programme 7th Framework Programme of the European Union Project No Duration Oct Sept Contact Main objective Find a way to regulate the immune responses following implantation procedures Partner countries France Germany United Kingdom United States Estonia Czech Republic Contents Protip Dr. Engin Vrana e.vrana@protipmedical.com Steinbeis-Europa-Zentrum Editorial, Immodgel in brief 1 Market needs in implant technology and Immodgel s relevance 2 Steinbeis-Europa-Zentrum: Immodgel s administrative coordinator 4 Publications and Events 5 Scientific coordinator Administrative coordinator Dr. Mercedes Dragovits dragovits@steinbeis-europa.de 1

2 Introduction Implants, transplants and engineered tissues are introduced to a host with the aim of recovering or regenerating a lost organ and tissue function. In the ideal case, these structures should be integrated seamlessly with the host tissues, which is impracticable for most implantable materials. This resulted in the search for biocompatible components that induce the minimal immune response possible by the host body. One of the most common examples of such materials are the bioinert titanium and its alloys. Titanium is a biocompatible material which has been shown to be a good substrate for mammalian cells. Porous titanium structures can be integrated with the host tissue, via tissue ingrowth (Figure 1, PKH-26 stained fibroblasts (Red) on Titanium microbeads ( y e l l o w ) as an invitro model of tissue ingrowth with fibroblasts, which are responsible for ECM secretion and Figure 1 A Porous titanium Implant in the process of being remodeling. covered by Fibroblasts (Image: H o w e v e r, Protip SAS/INSERM UMR 1121) even these materials can cause immune system related complications. It is known that some people are sensitive to titanium, while nearly % of humans are sensitive to metals such as chromium, nickel and cobalt which Market needs in implant technology and Immodgel s relevance are generally present in its alloys. Reactions to implants can be divided into two categories: i) hypersensitivity to the implant materials or their degradation products ii) inflammatory responses to the implant materials themselves and also to their debris products (even metals degrade to a degree within the body). Hypersensitivity to hip, joint and dental implants as well as pacemakers has been well documented. This can result in osteolysis, aseptic loosing and unsatisfactory osseointegration. This is generally related to corrosion that can be directly linked to the immune cell activity. This is highly relevant in implants as it has been shown that metal sensitivity of patients with failed implants can be up to 6 times higher than the population average. Inflammatory reaction to debris happens through the phagocytosis of the particles released from metallic, ceramic or polymeric implants. A certain amount of particle release and degradation are inevitable for nearly all implants. Particles in the size of hundreds of nanometers to a few micrometers can be phagocytosed by immune cells and cause reactivity. Following phagocytosis, a proinflammatory signal such as IL-1β is produced. Also, the NFκB pathway induced production of other pro-inflammatory signals e.g. TNF-α, IL-6 results in increased osteoclast activity (bone resorption). At the same time, it decreases osteoblast activity (less osteoblast differentiation by the resident stem cells, decreased crystallisation and ECM secretion activity, resulting in a significant reduction of new bone formation). Debris-induced immune activation results in aseptic inflammation. If this is not resolved properly and the debris is continuously produced, it can result in implant failure, such as aseptic osteolysis in the case of orthopaedic implants. Statistics on implant failures More than 1 kilotonne of titanium material is implanted in patients worldwide every single year. Although most of these implants do not cause significant discomfort to the patients, a 1% rate of complications still results in an enormous burden on the healthcare system. In the case of total knee arthroplasty, the clinical experience suggests around an 11% adverse reaction rate. However, there are reports stating that most of the implant revisions in the field are due to immune reaction related reasons such as metal allergy. 75% of Total Joint Replacement revisions are due to osteolysis with an occurrence rate of 5% in all replacement population. Figure 2 shows the lost bone area around a hip implant which results in complete loss of interface between the implant and the surrounding bone tissue (denoted by arrows). In addition to the infection related complications, about 5% of dental implants fail due to bad osseointegration. All these complications require revision surgeries, prolonged hospital visits and loss of working days along with a significant decrease in patient 2

3 Figure 2 Osteolysis around a hip implant and deconnection of the implant from the bone surface. From hss.edu quality of life. Overall, it can be said that complications add 10% to the total healthcare expenditure due to the essential revisions. Consequences of implant failure Upon implantation, an acute, transient inflammatory response is normal and actually necessary for removal of the damaged tissue and possible contaminants such as microorganisms. However, in some cases, this acute response turns into a chronic one resulting in patients to develop a persistent reaction to metal implants. This response is related to the material characteristics (grade, alloy components, structure, resistance to c o r r o s i o n etc.) and also partially to the patient s immunoprofile. It is predominantly macrophage-driven and in general a foreign body response mainly to debris produced by the implant. Allergy to metal implants may develop as a result of a pre-existing condition or it can be due to induced lymphocyte sensitisation. The most common consequences are persistent swelling, formation of seromas as well as delayed wound healing. The allergy related issues together with chronic inflammation related issues can cause dramatic problems, as can be seen in Figure 3 where severe osteolysis resulted in complete failure of a knee replacement together with surrounding tissue damage. Figure 3(A) (B) Radiographs of total knee replacement of a patient with severe osteolysis (caused fracture of the tibial baseplate). (C) The removed implant component. (Reproduced from Naudie DDR, Rorabeck CH. Instr Course Lect 2004; 53: ) Immodgel approach and impact Immodgel aims to develop an auxiliary system that can be applied to implants and will serve to control the immune response after implantation. By doing so, Immodgel aims to decrease chronic inflammation and support wound healing. This will result in a significant decrease in the implant complication related costs for the healthcare system while only causing a small increase in operation costs. Our second aim is to significantly improve the quality of integration and decrease its duration; thus improving the quality of life of the patients and the functionality of the implants. By achieving this, we can significantly decrease the implant related hospital stays and follow-up therapy. The Immodgel consortium is currently in the process of developing two diagnostic tools: 1. a personalised immunoprofiler which provides information about the patient s immune cell properties, allowing the personalisation of the implant accordingly and 2. an on-chip system which provides the patient specific reaction to a given implant material. Through these diagnostic systems we hope to achieve a personalised medical solution to immunomodulation. References: 1. Nasser S. Immune hypersensitivity to orthopedic biomaterials. Presented at: Smith & Nephew 12th Annual International Knee Meeting; October 4, 2002; Rome, Italy. 2. Hallab N, Jacobs JJ, Black J. Hypersensitivity to metallic biomaterials: a review of leukocyte migration inhibition assays. Biomaterials. 2000; 21: biotinet.eu/downloads/1st%20workshop%20slovenia/biotinet_korosec.pdf 3

4 As part of the Steinbeis Innovation ggmbh, the Steinbeis-Europa- Zentrum (SEZ) is the operational unit of the Commissioner for Europe of the Minister of Finance and Economy in Baden-Württemberg. The non-profit organisation was founded in March 1990 and has since then evolved into an experienced technology transfer centre with offices located in Stuttgart and Karlsruhe. Its qualified 56 staff members engage in the promotion of European RTD programmes and the support of industry and SMEs as well as higher education establishments in Baden-Württemberg. The SEZ staff is trained in project management, exploitation and IP rights as well as in dissemination and communication of research results. In the last years, SEZ was involved in more than 40 European projects (as partner and/or coordinator) including Small- and Medium Scaled Projects (STREP) and Coordination and Support Actions under the 7th framework programme and Horizon Steinbeis-Europa-Zentrum: Immodgel s administrative coordinator The core activities of SEZ are: to assist organisations in their participation in European R&D projects; to support the management of international research projects; to give assistance in the exploitation of research results; to promote trans-national technology transfer; to stimulate and support the innovation process in industrial companies project management and coordination. Role in Immodgel As project coordinator, SEZ is in charge of Immodgel s administrative and financial management. SEZ additionally leads a Work Package on Dissemination, Exploitation and Management of Intellectual Property (IP), implementing the constant knowledge transfer within the consortium. It is responsible for the creation and regular updating of Immodgel s website immodgel as well as the production of the project's flyer and half-yearly newsletter issues. Moreover, it moderates regular internal IPR-Workshops and performs periodic patent searches while drafting Immodgel s exploitation plan. Main staff members involved in the Project Dr. Mercedes DRAGOVITS obtained her PhD in Biology (with focus on cell biology and nanotechnology) at the University of Heidelberg, where she earned experience in interdisciplinary research projects and research cooperations. As Immodgel s Project Manager, she is responsible for the project s coordination, administrative and financial management, dissemination, IPRmanagement, technology watch and event management. Dr. Sabine MÜLLER earned a PhD in Biology and Master in Innovation s Management (Innovative projects engineering). As Project Manager and consultant specialised in Micro and Nanotechnologies, she coordinated the writing of Immodgel s proposal and was involved in its proofreading, quality checking and submission. Kathrin ECKERLIN earned a Master s degree in Public Administration and European Governance. In her role as Immodgel s Project Assistant, she was in charge of the organisation of the Kick-Off-Meeting in Karlsruhe and the production of the project flyer as well as the newsletter. Additionally, she coordinates the regular internal reporting as well as the periodic reports to the European Commission. Contact Dr. Mercedes Dragovits, Admin. Coordinator dragovits@steinbeis-europa.de Kathrin Eckerlin eckerlin@steinbeis-europa.de steinbeis-europa.de 4

5 Publications Past Events You can find links to all our press releases under immodgel/news.html The first review article is available under hindawi.com/journals/bmri/2014/921905/ Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances, J. Barthes, H. Özçelik, M. Hindié, A. Ndreu-Halili, A. Hasan and N. E. Vrana TERMIS June 2014, Genova (Italy) Dr. Barthes (University of Strasbourg) gave a presentation on the adhesive surface for the implant/gel interface. The congress was organised by the Tissue Engineering and Regenerative Medicine International Society at the Magazzini del Cotone Conference Center. Two further articles have been recently accepted for publication by Biomaterials Science and the Journal of Immunology. Upcoming Events Lecture at the European School of Chemistry, Polymers and Materials Science 17 Dec. 2014, Strasbourg (France) Dr. Engin Vrana (Protip) will give a lecture on Cellular Reactions to Implant Materials at the European School of Chemistry, Polymers and Materials Science in Strasbourg. Next IMMODGEL Partner Meeting Date TBD, Brussels (Belgium) The next partner meeting is planned for mid of 2015 in Brussels. Workshop Improving the opportunities for EU and US businesses to collaborate in health Research & Innovation Projects: Exchange of Good Practices 20 June 2014, Boston (US) Dr. Vrana (Protip) was invited to present the Immodgel project during the session on Showcases of transatlantic business collaboration (health/ e-health field) in RTDI: Exchange around real-life experience in transatlantic RTDI collaboration of companies and sharing of good practices, barriers and drivers. M12 IMMODGEL Partner Meeting Nov. 2014, Nottingham (UK) The 12 month partner meeting took place on November 2014 in Nottingham and was organised by the University of Nottingham with the support of SEZ. The partners presented their work progress so far and discussed the main activities planned for the next 6 months. 5