The project: Patim
Man-made artificial replacements for cardiovascular disease like heart valves and blood vessel prostheses have become indispensable in modern medicine. A major problem however, is the response of the immune system which recognizes these synthetic structures as foreign and will start trying to remove it. This thus limits the use of these cardiovascular implants. There is also a lack of proper connection by these implants to the healthy tissues of the recipient (reendothelialisation).The current trend in the field of implantology is towards “bionaturalizing” these artificial replacements. The consortium, PATIM, has set as its goal, the production and optimization of patient optimized or autologous implants. Here two strategies are employed
a) The synthetic structures will be provided with functional groups which will allow conjugation to e.g. cells in order to minimize adverse immune reactions (functionalized implant surfaces)
b) The implants will be synthesized in vitro from completely autologous cells.
The main task of PATIM will thus be the bionaturalization of cardiovascular implants. In the preclinical stage, information on inflammatory responses to the implants are gathered and processed in order to develop new immunotherapic strategies aiming to prevent or minimize rejection and improve the integration of the implants in the host organism.
The task of EMI will be to:
- Determine the underlying inflammatory processes related/relevant to the foreign synthetic structures
- Determine the biological degradation pattern of the implants
- In particular determine the behavior of inflammatory and wound healing macrophages
- Use this information to generate ideas how to modulate the implantat-related immune response
New findings suggest that drastic reactions of the immune system can be positively influenced through modeling or depletion of macrophages. In the first instance the role of immune effector cells (especially macrophages) will be investigated using specific binding ligands as molecular probes, using the CD64 receptor on the macrophages as a target. The binding will be done via a recombinant antibody coupled to a SNAP-tag whose structure is derived from a DNA repair enzyme and allows a stoichiometric and covalent coupling to benzyl guanine modified substrates with high efficiency under physiological conditions. Upon labeling the recombinant binding ligands (antibodies) retain their maximum functionality.
Selected SNAP-tag fusion proteins will be used to evaluate the migration of immune effector cells (macrophages) into the tissue environment of functionalized implant surfaces. Another evaluation of the immune response, and the success of the modified surfaces of the implant will be done after implantation using histological, immunohistochemical, and PCR based techniques.
Patim was selected as part of the ERDF co-financed operational program for NRW in Objective 2 "Regional Competitiveness and employment" 2007-2013.
