Final Report Summary - MULTITERM (Training Multidisciplinary scientists for Tissue Engineering and Regenerative Medicine) Executive Summary:The ageing population in the EU requires the development of new treatment strategies for diseased, defective, or damaged tissues. MultiTERM aims to deliver 13 highly skilled, multidisciplinary trained scientists to the field of tissue engineering and regenerative medicine. These scientists will develop smart materials that can be used to replace and repair tissues. Moreover, they will examine and conceive improved imaging methods to visualize the fate and effects of these implants. This will enhance our understanding of tissue remodelling and reduce the number of experimental animals since longitudinal studies will become possible. The scientists are expected to be able to cut across traditional fields of study and understand completely different aspects - ranging from material choice, cell biology, to clinical translation - in order to successfully design and clinically implement engineered tissue. To achieve these goals 13 ESR were recruited for the 5 host institutes in the network. Highly complementary, cross-sectorial skills training was offered: the ESR have followed 6 Multidisciplinary Research Skills Training Workshops and 9 Generic Courses in a range of generic, transferable skills designed to improve their employability and career mobility. Additionally, ESR have followed supplementary courses necessary for their individual development, and have travelled to host institutes for their secondments. Work package 1. Biocompatible and biodegradable materials: a cornerstone of Tissue EngineeringThe ESR have successfully developed large scale purification processes for naturally derived polymers which will be employed for soft tissue engineering. Additionally, new materials were developed for a variety of tissue engineering purposes. For bone-tissue engineering, synthetic gels were adapted, and novel bone substitutes were developed. A composite gel was designed to deliver essential growth factors to enhance cartilage formation and calcium phosphate-based cements were further adapted to permit imaging of the bone regenerative process. Additionally, injectable gels were prepared to serve in minimal invasive procedures and a skin substitute was prepared. Finally, hybrid scaffolds were produced for soft tissue engineering that combine the favourable biologic characteristics of collagen with the favourable mechanical characteristics of knitted polymer materials.Work package 2. In vitro preparation of matricesThe materials developed in WP1 have been tested extensively in vitro to test for cytocompatibility and adverse effects. Cells from surgical specimens were isolated and combined with various scaffolds under predefined conditions to test the behaviour of the scaffolds, and to test the interaction between cells and scaffolds. A decrease of collagen content combined with a polymer mesh for mechanical strength resulted in a collagen scaffold with superior biocompatibility characteristics. Additionally, mechanical characteristics were studied to test compliance, flexibility and strength. A unique inflation method was used to test the strength of a glue under extreme stress condition. Bioreactor experiments have been initiated to test the various constructs under study. Finally, extracellular matrix containing constructs were prepared aiming at the construction of of-the-shelf scaffolds. The experiments performed in WP2 have demonstrated that the developed biomaterials can be used for their designed purpose.Work package 3. Vascularisation of engineered tissueOne of the biggest challenges in tissue engineering is adequate vascularization. Prevascularization of materials might solve this issue. To this end primary human endothelial cells were isolated from peripheral blood samples, differentiated and their phenotype determined. The collaborative effort of the ESR at UZH and UBSH has lead to comparative studies of vascularization by endothelial cells and stromal vascular fraction-derived cells, showing different structural features between vascular structures generated by blood-derived endothelial progenitor cells mixed with skin fibroblasts and stromal vascular fraction-derived cells. These studies are instrumental in better understanding neovascularization. Finally, a 3 cm diameter prevascularized fibrin hydrogel was prepared by co-culturing primary endothelial cells and fibroblasts. Further upscaling is ongoing. Work package 4. Non-invasive imaging of engineered tissueOne of the aims of MultiTERM is to develop imaging modalities to monitor the fate of biomaterial after implantation. Different approaches have been studied to achieve this aim: materials loaded with nanoparticle sized Super Paramagnetic Iron Oxide (SPIO) particles revealed a significant contrast, and in vivo experiments have been initiated to study the fate of scaffolds used for bladder augmentation in rats. Additionally, hydrogels were chemically modified to achieve 19F MR imaging. Inclusion of a contrast agent into bone cement as developed in WP1 allowed a clear localization of the defect site, allowing longitudinal follow-up (reducing animal use) and visualization of new bone formation. Work package 5. Training ObjectivesThis workpackage is obviously a vital part of MultiTERM. 9 generic courses and 6 workshops with hands-on experience have been given. The courses were designed in such a fashion that they would benefit the ESR in the early stage of their projects. Expected final results, potential impactMultiTERM expects to deliver various new materials for different tissue engineering applications ranging from skin substitutes to bone cements. A number of new materials with great potential have been developed by MultiTERM ESR. It is anticipated that these new materials will significantly decrease animal use and it is likely that part of the developed materials will be further developed for clinical implementation. Thus, we serve four major objectives: i. development of new materials for tissue engineering purposes for new treatment strategies, ii. development of imageable new materials to follow the fate of engineered tissues, iii. reduction of animal usage and iiii. strengthening the economic potential of Europe. MultiTERM is also expected to deliver 13 highly skilled, multidisciplinary trained scientists to the field of tissue engineering and regenerative medicine, strengthening the European work force. The results of MultiTERM research are disseminated through publications in peer reviewed journals and the public accessible website www.multitermproject.eu.Contact InformationFor more information, please contact the coordinator Dr. E. Oosterwijk (tel. +31-24-3614907, e-mail e.oosterwijk@uro.umcn.nl) or visit the website: http://www.multitermproject.eu/
