CONTROLLED HOST BODY RESPONSE FROM BIOMATERIALS THROUGH INTRINSICALLY DISORDERED PROTEINS (IDPs) INTERACTION

The body will automatically be rejected if materials that are placed into the human body, however scientist have developed materials that suppress this reaction. In the news before Christmas, many European newspapers reported on indecencies that several medical devices (pacemakers, stents, breast implants, hip joint implants did not behave as they should, and many implants had to be removed, which is detrimental to the patient. This project has focused on how to modify surfaces of medical devices by adding certain proteins to improve the reaction with the patient. Which proteins attach themselves can determine how implants will work and what kind of cells are attracted to the surface. Therefore, it is very important to understand how protein is attached and how they look on surfaces. It has been a theory that proteins that are disordered (Instrinsic disorder proteins, IDP) may have such a positive effect. We have shown in this project that we have been able to attach such IDPs to surfaces for biomaterials and that cells that come to this surface like it better than surfaces without IDP. We also know in animal studies that bones grow faster on such surfaces.

This successful project outcome expects to have a great impact on the quality of life for a very large proportion of European citizens and will at the same time unburden the already strained European health care resources. Increased success for bioactive material interaction with bone will improve the people's confidence in the technique and reduce the damage done. The increase in the aging population and increasing number of injuries are the major drivers that positively affect the demand for the implants. Improved medical implants and devices to aid surgical repair of difficult to treat fractures will continue to play a crucial role in increasing the quality of life and in saving the lives of many thousands of patients across the EU. Effective solutions, which provide for extended, productive, quality lifespan and simultaneously reducing costs for the public sector. This project was a significant step in this direction

Adverse immune reactions and resulting severe inflammation (acute or chronic) cause a significant challenge in modern biomedicine. The cost of revisions of e.g. hip implants alone costs between 15-30 kEuro per procedure and runs in the billions of Euro pe r year in the Euro zone [1]. The IMPRovE project aims at investigating the adsorption of intrinsically disordered proteins (IDP) in adverse immune reactions to particular designed titanium surfaces. IDPs have lately been shown to play important roles in m odulating immune reactions[2], in immune recognition[3], and in controlling calcification[4]. However, new results show that also the unstructured or disordered regions can be crucial to protein function[5]. The role of these IDPs in adverse immune reacti ons to material surfaces has so far not been studied. The IMPRovE project will utilize advanced techniques such as Atomic Layer Depostion (ALD) to deposit specific chemical surfaces without altering topography. In the traditional surface modifications of e.g. titanium, it is difficult to alter chemistry without changing the topography. Interactions between specific IDP sequences and material surface candidates based on both chemical and nano-topographical modification will be modelled and tested experime ntally to provide new strategies for utilizing surface recognition events to improve biomaterial performance. Potential surfaces will then be tested in vitro and then further examined in an establish rabbit model. This will provide new knowledge will fo rm the basis for innovative strategies to improve the biological performance of biomaterials and provide novel treatment strategies to combat adverse immune reactions, reactive calcification and rejection processes. The innovative track-record of the PI a nd the strong infrastructure with established methods at the host institution will greatly increase the chances of realizing this proposed project.