Generation and imaging of patient customized implants J.Frese 1 , P. Schuster 2 , ME. Mertens 3 , A. Vogg 4 , A. Morgenroth 4 , B. Zlatopolskiy 4 , U. Dahlems 5 , L. Rongen 1 , S. Koch 1 , P. Mela 1 , G. Melmer 5 , S. Barth 6 , FM. Mottaghy 4 , T. Schmitz-Rode 7 , T. Lammers 3 , S. Jockenhoevel 1,2 , F. Kiessling 3 1 Deparment of Tissue Engineering & Textile Implants, Institute of Applied Medical Engineering, Helmholtz Institute of Biomedical Engineering, RWTH Aachen University, Aachen, Germany 2 Department of Tissue Engineering & Textile Implants, Institut für Textiltechnik, RWTH Aachen University, Aachen Germany 3 Department of Experimental Molecular Imaging, Helmholtz Institute of Biomedical Engineering, RWTH Aachen Uni- versity, Aachen, Germany 4 Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Aachen, Germany 5 Pharmedartis GmbH, Aachen, Germany 6 Department of Experimental Medicine & Immunotherapy, Institute of Applied Medical Engineering, Helmholtz Insti- tute of Biomedical Engineering, RWTH Aachen University, Aachen, Germany 7 Institute of Applied Medical Engineering, Helmholtz Institute of Biomedical Engineering, RWTH Aachen University, Aachen, Germany Abstract Personalized medicine is the development of individual solutions and therapies tailored to the specific disease pattern of a patient. To enable patient customized medical solutions 40 partners of the Aachen Research Cluster “innovation med i- cal technology in.nrw” are investigating a new generation of biomedical devices and systems. The subproject Patim ad- dresses non-invasive monitoring techniques to observe dynamic changes in tissue engineered cardiovascular implants. 1 Introduction Over the last decade, remarkable progress has been made in the field of cardiovascular tissue engineering. The ap- proach to combine cell seeding with natural or synthetic scaffolds to create implants with proper mechanical, struc- tural and functional properties could be shown particularly applicable to small calibre vascular grafts in pre-clinical [1] and clinical studies [2]. Small calibre substitutes are used for peripheral and cardiac revascularization proce- dures to overcome the shortcomings of currently available synthetic grafts, including thrombus formation resulting in poor patency rates, infection and lack of growth and re- modelling potential. To minimize the risk of life- or limb- threatening conditions, these grafts are clinically evaluated as model for arteriovenous (AV) shunts [3]. Tissue engineered implants undergo remodelling processes within the construct itself and with the surrounding host tissue. Haemodynamic forces act at ex vivo generated neo- vascular tissue and lead to the degradation of scaffold ma- terial and synthesis of extracellular matrix proteins. During this maturation process changes at the cellular and molecu- lar level can adversely affect the anatomy and function of the graft. To obtain insights into such processes, extensive animal experiments have to be performed, requiring the sacrifice several animals at each observation time. Howev- er, the obtained results represent the state of the implant at that specific time point and do not depict the dynamic lon- gitudinal remodelling process. Such changes still remain hidden due to the lack of non-invasive monitoring possibil- ities. For the clinical translation of these highly innovative tissue engineered implants online and longitudinal moni- toring is crucial to record inter-individual processes and to counteract potential pathological changes at an early stage. The aim of our work is the generation and imaging of pa- tient customized cardiovascular implants. Therefore func- tional and molecular imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomogra- phy (PET) are combined to gain continuous information about the functional and cellular state of the implant. Fur- thermore, a targeted therapy is developed to reduce or spe- cifically destroy activated macrophages. The online moni- toring will enable the delivery of such therapy at the earli- est detection of an inflammatory process at the site of the implants. 2 Methods 2.1 Visualization of cells and textile scaf- fold by MRI To enable MR imaging, the incorporation of contrast agents into textile scaffolds and / or endothelial cells used for the ex vivo colonization of the grafts appears a simple and suitable method to provide enhanced visibility for tis- sue- engineered implants. Ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) are favourable cell markers, since they present strong T2 and T2* contrast, and therefore allow sensitive and long-term tracking of labelled cells. However, conventional USPIO without sur- face functionalization show only low cell internalization rates, so that high USPIO concentrations or transfection agents are required to effectively label the cells. These Biomed Tech 2012; 57 (Suppl. 1) © 2012 by Walter de Gruyter · Berlin · Boston. DOI 10.1515/bmt-2012-4388 Unauthenticated Download Date | 7/29/18 10:37 AM