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Welcome to the MultiTERM website MultiTERM is a Marie Curie Initial Training Network (ITN) on ‘Training Multidisciplinary scientists for Tissue Engineering and Regenerative Medicine’. It is a four year project funded by the European Commission and bringing together 4 renowned research institutes and 1 SME, each specialized in different aspects of tissue engineering. The overall objective of this project is to provide a training network for early stage scientists to deliver a number of excellently trained, highly employable scientists for companies and academia in the field of tissue engineering and regenerative medicine (TERM). MultiTERM has recruited 13 Early-Stage-Researchers (ESR, PhD students) at 5 partner organisations in 3 European countries. The hosts organizations are: Radboud University Nijmegen Medical Centre, The Netherlands Uppsala University, Sweden University Hospital Basel, Switzerland University of Zürich, Switzerland EMCM B.V. (European Medical Contract Manufacturing B.V., FKA aap BioImplants Netherlands BV), The Netherlands The MultiTERM programme officially started on October 1, 2009. Through this website, we will keep you informed about the progress of our research and training network. Yours sincerely, Dr. Egbert Oosterwijk Coordinator MultiTERM Associate Professor of Experimental Urology These pages are best displayed with Internet Explorer for Windows and Firefox for all platforms

Training Multidisciplinary scientists for Tissue Engineering and Regenerative Medicine MultiTERM is a training network providing multidisciplinary training for 13 early stage scientists in 5 host institutes that will deliver a number of excellently trained, highly employable scientists for companies and academia in the field of tissue engineering and regenerative medicine (TERM). The aging population of the EU requires the development of new treatment strategies for diseased, defective, or damaged tissues. Since donor material is often not available, artificial tissue needs to be developed for these purposes. Therefore, smart materials that can be used to replace and repair tissues should be developed. With better tissue engineering possibilities becoming available, improved methods to visualise the fate and effects of these implants are essential and need to be examined. TERM is a multidisciplinary field where scientists need to cut across traditional fields of study. They need to understand completely different aspects - ranging from material choice, cell biology, to clinical translation - to successfully design and clinically implement engineered tissue. Unfortunately, such scientists are scarce, because such TERM-specific interdisciplinary training is missing. To fill the gap that currently exists, the MultiTERM Network will provide early stage researchers with individual and centralized training in key elements of TERM: biomaterials, cell biology, bioreactors, animal modeling, clinical and industrial translation. The MultiTERM Partners, including the industrial partner, are recognized leaders in their fields - ensuring state-of-the-art training - with highly complementary, cross-sectorial skills, and have extensive prior FP experience, assuring achievement of this goal. During their training, the early stage scientists will develop new materials and implants for tissue engineering as well as state-of-the-art novel visualization procedures to monitor the behaviour of the implanted tissues. Figure 1: Outline of MultiTERM

With an increasingly aging population, tissue engineering and regenerative medicine will become of eminent importance in maintaining an active and healthy population in Europe. Tissue engineering aims at the development of biological products that repair, regenerate or replace tissues and/or organs (e.g. skin, bone, muscle etc.). To achieve this goal, new materials need to be developed for both hard and soft tissue engineering (e.g., with self-instructive properties) and one of the largest bottlenecks towards the routine clinical use of tissue engineered products, namely the use of autologous cells needs to be eliminated. With enhanced tissue engineering possibilities, development of non-invasive methods to monitor the fate and effect of the used implants is of utmost importance. Imaging of engineered implants is a largely uncharted field. Current evaluation of engineered tissue in animal models generally includes histological evaluation at predetermined time after graft implantation. In humans, second-look surgery may be performed to demonstrate efficacy of anti-adhesion materials used to prevent adhesions that often develop after a surgical procedure. Clearly, invasive methods are undesirable. Non-invasive procedures offer the possibility of longitudinal follow-up, which is of much greater value: it provides crucial information on the outcome and result of the procedure. Secondly, it offers insight in the biological behaviour of the tissue implants and their degradation over time, tissue viability, vascularity, and perfusion. Finally, non-invasive methods for follow-up reduce the number of animals necessary to study the behaviour of the engineered tissue in the preclinical phase.

In this project partners will train ESR in multiple aspects of Tissue engineering and Regenerative Medicine through individual research training supplemented by a program of courses in complementary transferable skills and Research Skills Training Workshops related to hard and soft tissue engineering to ensure appropriate knowledge of these related areas. The complementary skills of the individual partners – all recognized leaders in their field – and integration of short term scientific missions to network partners of all ESR will further foster their multidisciplinary views, and will create new collaborations between partners. As a result of their training the ESR will be highly skilled in different research areas required for tissue engineering, able to understand and speak different scientific languages. Additionally, new materials and implants for tissue engineering as well as state-of-the-art novel visualisation procedures to monitor the behaviour of the implanted tissues will be developed. The work plan for this project consists of 5 work packages (WP). Materials developed in WP1 will be further optimized in WP2 (preparation of (smart) matrices) and WP3 (development of prevascularized grafts and development of extracellular matrix containing grafts). In parallel, and in close association with WP1, 2, and 3, non-invasive imaging of engineered tissue will be studied in WP4. For the sake of clarity, key aspects of the research training programme are presented in a separate workpackage (WP5).

Workpackage 1 Biocompatible and biodegradable materials: a cornerstone of Tissue Engineering In this workpackage materials for soft and hard tissue engineering will be developed. Naturally derived polymers from other sources including polysaccharides, polypeptides and polynucleotides are attractive potential alternatives that bring novel properties for tissue engineering. Much effort is therefore placed on developing implantable quantities from such biomaterials (e.g. starch, gelatine, chitosan, carrageenans and alginates). The hurdles of removal of endotoxines, reproducible production and assurance of biocompatibility and non-toxic degradation products in-vivo, have so far limited their applicability for in-vivo use. A low-cost full scale process for low endotoxin and ultrapure biopolymers and depyrogenisation & purification of other biopolymers will be developed, leading to the production of a bioadsorbable anti-adhesion product. Additionally, synthetic gel precursors will be developed and characterized leading to gels for cartilage and – after detailed bone induction studies – gel applicable to osteoporosis fractures. Novel instructive bone substitutes will be developed as well as novel labelling strategies for the labelling of hydroxyapatite (eg iron substitution in calcified matrix for the labeling of hydroxyapatite, crystals or iron oxide nanoparticles for seeded cells). A bi-layered collagen scaffold for bladder reconstruction will be prepared. Distinct biodegradable matrices and scaffolds which serve to optimally support proliferation and differentiation of keratinocytes, melanocytes, endothelial cells and fibroblasts obtained from material of human subjects will be tested leading to the development of the optimal scaffold design for skin substitutes, leading to the production of a clinically applicable, large dermo-epidermal substitute. Finally, a surgical invasive device used to prevent postoperative and posttraumatic bone, soft tissue and joint infections and an aneurysms treatment product based on alginate and Type-1 collagen.

Workpackage 2 In vitro preparation of matrices In this workpackage materials developed in WP1 will be further adapted to specific needs. The development of smart and instructive matrices and handling logistics and cost of autologous cells represent major challenges towards the routine clinical use of tissue engineered products. With each tissue having its own unique set and content of scaffold bio-molecules, selective incorporation of biologically active molecules may be necessary. In this workpackage smart matrices will be developed (various pore sizes, interconnectivity levels, addition of growth factors) and tested in vitro and in bioreactor settings and combined with pre-vascularised bi-layered matrices (see workpackage 3) leading to bi-layered cell seeded matrix. Collagen scaffolds will be substituted with heparinsulfate (HS) and HS-binding growth factor epidermal growth factor (EGF). A porous collagen scaffold containing elastin fibers for elasticity, dermatan sulphate and heparin sulfate will be combined with specific growth factors (bFGF and VEGF) to stimulate proliferation of fibroblasts and angiogenesis. Prevascularised bilayered matrix seeded with cells will be evaluated in vitro and the most optimal scaffold tested in vivo. For foetal membranes deployment of solid or injectible plugs into membrane defects under wet gluing conditions will be tested and evaluated after defining the critical membrane defect size that leads to rupture of foetal membranes. Two materials to close foetoscopic puncture wounds will be studied: (1) solid, preformed biomaterial scaffolds for plugging (collagen plugs, RUNMC; de-cellularized human amnion, UZH) (2) injectible, in situ forming hydrogel polymers that slowly resorb and function as physical sealant of the entry wound. Central to these investigations is a novel experimental platform that permits to perform sealing tests on human foetal membranes ex vivo. The best performing sealant will be evaluated for MRI particle loading, leading to the identification of a scaffold or injectible sealant that functions as sealant under wet gluing conditions with superior bonding and integration properties of plug material in foetal membranes, and deliver scaffolds or injectible sealants for membrane defects that could be monitored by MRI in vivo. For osteogenic grafts, extracellular matrix (ECM) laid down by appropriate cell lines during in vitro culture may be sufficient to induce tissue regeneration, even in the absence of the living cells. For this purpose suitable cell lines will be defined aimed at eliminating the use of autologous cells. After determining appropriate scaffold and culture conditions, a de-cellularization procedure will be developed, leading to a protocol for efficient generation of ECM-containing grafts and differently sized grafts, and a protocol for the generation of cell-free osteogenic grafts. Subsequently, these grafts will be tested in an animal model.

Workpackage 3 Vascularisation of engineered tissue Research in this workpackage will concentrate on the development of methods to improve the vascularisation of engineered tissues. To overcome a major limitation related to the use of most tissue substitutes – their lack of a vascular plexus – a pre-vascularised graft will be developed. We hypothesize that pre-vascularised grafts, will be perfused significantly more rapidly than an initially avascular construct, greatly enhancing their engraftment and performance. After successful isolation of angioblasts using immune-panning techniques to isolate putative angioblasts from the leucocyte fraction of peripheral blood of humans, comparative studies, and induction of lumenized capillaries a 3 cm diameter pre-vascularised hydrogel will be developed, eventually leading to the development of a 10 x 10 cm pre-vascularised gel. To produce these clinically applicable prevascularized gels, a stabilizing highly porous biodegradable scaffold has to be developed. The prevascularized scaffolds will be tested for the engineering of complex dermo-epidermal substitutes. In addition the prevascularized matrices will be combined with unmodified bi-layered scaffold, leading to the construction of a bi-layered construct. Accelerated and enhanced engineered osteogenic graft vascularisation will be developed by supporting co-culture of osteogenic cells with endothelial progenitor cells in streamlined manufacturing processes focusing at defining culture techniques for 3 different levels of maturation/organization. Additionally, scaffold and culture conditions in bioreactor environments for optimal extracellular matrix deposition will be defined. The most suitable level of maturation for implantation and definition of the maximal size of the grafts will be identified.

Workpackage 4 Non-invasive imaging of engineered tissue To permit non-invasive imaging of engineered tissue, such as by micro-computed tomography (µCT) and/or magnetic resonance imaging (MRI) novel labelling strategies for the labelling of hydroxyapatite will be developed, as well as cell labelling strategies. Imaging of osteogenic grafts will require the selection of contrast agent and imaging method. Using novel labelling methods for MRI analysis, the osteogenic properties of novel instructive bone substitutes will be analysed in vivo. MR perfusion and FDG-PET images of engineered tissue in animals will be obtained, including longitudinal studies. Optimal acquisition methods for high resolution, diffusion and perfusion imaging of engineered tissue, matching with FDG-PET imaging will become available; imaging of contrast targeted engineered tissue and imaging results of longitudinal studies in an animal model will be obtained. The fate and performance of implanted bi-layered cell seeded matrix for bladder replacement will be evaluated. Synthetic gels will be tested in vivo for repair of cartilage and osteoporosis fracture and imaged. After optimization experiments performed on animal cadavers, in vivo evaluation in live animals will be performed, after approval. The effects of these gels will be investigated in large animals with closed fractures, including MRI imaging. Response to added growth-factors to hydrogel compound will be evaluated for the impact on fracture healing and eventual effect on non-wanted ectopic bone formation at the implantation site. Preparations for clinical trials for alveolar cleft procedures and sinus augmentation will be initiated. Functional connection of engineered vessels to existing vessels in the wound bed will be studied by MRI. The best performing sealant for foetal membrane ruptures will be evaluation for MRI particle loading. Contrast agent and imaging methods to analyse non-mineralized ECM deposited within the pores of 3D scaffolds will be developed. Critically sized grafts in the optimal maturation state for implantation will be prepared and tested in vivo. After validating the most adequate intra-abdominal adhesion animal model the optimal imaging technique for intra-abdominal adhesions will be determined using fluorinated materials and nano-tube labelled scaffolds to further enhance MRI possibilities, leading to the possibility to identify intra-abdominal adhesions with non-invasive imaging techniques. Sealants for membrane defects that can be monitored by MRI in vivo will be developed. These studies will lead to the development of non-invasive monitoring possibilities for engineered tissues, providing essential information on the morphological state, the fate of degradation, the biological behaviour of tissue engineered constructs, and tissue viability. Moreover, the development of imaging possibilities provide an excellent opportunity to investigate safety of products that consist of a combination of living cells, natural or synthetic materials and bio-molecules (Tissue Engineered Medical Products, TEMPs).

Workpackage 5 Training Objectives The network as a whole undertakes to provide a minimum of 468 person-months of Early Stage and Experienced Researchers whose appointment will be financed by the contract. Quantitative progress on this, with reference to the table contained in Part C and in conformance with relevant contractual provisions, will be regularly monitored at the consortium level. The research program will provide excellent interdisciplinary research training for 13 early stage researchers (ESR). The ESR will be provided with knowledge of interrelated fields necessary to fully grasp aspects of tissue engineering, bring them at a theoretical and practical knowledge level so that despite different backgrounds they understand each others ‘language’ and can jointly successfully execute the proposed research program. The ESR will be trained in aspects important for soft as well as hard tissue engineering. The international dimension of the network will be used to encourage transnational mobility and collaboration in our researchers, with secondments as obligatory part of the individual research programs. All Partners will contribute to the training program, and the distribution of tasks matches Partners’ expertise. RUNMC will be responsible for the organisation of the Complementary Skills Training Workshops in collaboration with other partners (including the industrial Partner). Dedicated partners will be responsible for the organisation of the Research Skills Training Workshops. The training program will be shaped according to the international PhD program of the Nijmegen Centre of Molecular Life Sciences (NCMLS, partner 1). All ESR are expected to finish a PhD thesis, including ESR employed at the industrial partner Aap. To achieve our goals the strong training provided by personalized research projects will be complemented by Multidisciplinary Research Skills Training Workshops. These consist of a mixture of lectures, interactive work in small groups, literature study, group discussion, hands-on experience on specialized equipment and written reports. To facilitate and enhance transfer between courses and workshops, course participants will be obliged to use examples from other workshop areas when taking a course, forcing the participants to use their new vocabulary in front of others. ESR will also receive complementary training in a range of generic, transferable skills designe to improve their employability and career mobility. These generic courses consist of lectures, journal clubs, literature studies, group discussions and written reports. In view of the objective to train ESR in interrelated and complementary fields necessary to fully grasp aspects of tissue engineering, all ESR will take at least 1 secondment in another partners’ laboratory. Thus we will exploit the complementary expertise of network members at the maximal level. Furthermore, our researchers will take secondments appropriate to their specific needs. Each ESR will have a local Personal Supervisor who will have primary responsibility for their supervision and progress. In addition, they will be assigned a local Advisor plus a Tutor from a Partner institution in the Network. The Advisor and Tutor will provide additional support and advice on the researcher’s research, training and career progression on a biannual basis, ensuring effective integration of ESR into the network. It will also ensure that they will be duly informed of contractual rights and obligations, possibilities offered to contribute to training events etc. The progress of all ESR will be monitored formally throughout the program. Each will complete a PDP that sets out their training needs and scientific objectives, records their progress with their research project, research training, transferable skills training and career development. The Network Training Committee will review these PDP Plans at six-month intervals with a view to implementing corrective action where necessary.

The MultiTERM Network will provide the ESR with invaluable training in various disciplines of tissue engineering, ranging from matrix development to commercialization and clinical training through our workshops, secondments and networking activities. Level of satisfaction of trainees will be measured by questionnaires which will be evaluated by the network training committee and the PhD Fellow board. The results of the evaluation will be communicated with the organizers and improvements will be installed (if necessary) after consultation. In this way we will generate a strong cohort of confident, highly employable young scientists capable of contributing effectively to the knowledge-based European economy. A Network Training Committee will review and assess the progress of the researchers periodically (on the basis of short six monthly reports) and will ensure that progress is made for the Personal Career Development Plan (PDP). The MultiTERM Network training committee will monitor the selection, supervision, training, progression and PDP of our ESR. This should ensure best practice across the network. Each ESR will have a local Personal Supervisor who will have primary responsibility for their supervision and progress. In addition, they will be assigned a local Advisor plus a Tutor from a Partner institution in the Network. The Advisor and Tutor will provide additional support and advice on the researcher’s research, training and career progression on a biannual basis. ESR will be part of the network training committee on a rotating basis. The progress of all ESR will be monitored formally throughout the program. They will present talks on their work and communicate with their tutors by telephone/email on a bi-monthly basis, and meet at annual meetings. Each will complete a PDP that sets out their training needs and scientific objectives, records their progress with their research project, research training, transferable skills training and career development. The Network Training Committee will review these PDP Plans at six-month intervals with a view to implementing corrective action where necessary. In view of the objective to train ESR in interrelated and complementary fields necessary to fully grasp different aspects of tissue engineering, all ESR will take at least 1 secondment in another partners’ laboratory. The secondments are an integral part of the individual research plans, thus ensuring exchange and the gain of experience of a different discipline. Most secondments are placed in year 2 of the funding period to give the ESR the possibility to first become fully acquainted with methodologies in their home institute and gives the ESR the opportunity to define and design experiments that will be performed during the secondment. This timing also permits the ESR to optimally benefit from their gained skills during their secondment and implement this knowledge while returning to their home institute. Furthermore, our researchers will take secondments appropriate to their specific needs. Additionally, ESR will be trained through several other routes. Firstly, all ESR will contribute to our discussions of research activities at our regular annual meetings. Secondly, the secondments that are integral part of the individual training programs will help them assimilate new technical know-how, enhance their career development, and promote MultiTERM networking. ESR will be expected to attend, present their work and contribute to meetings, particularly the annual meetings of the Tissue Engineering and Regenerative Medicine International Society – TERMIS-EU Meeting. In the last year we will organize a separate session during the TERMIS-EU meeting where the ESR can showcase their achievements.

Expertise This project will be part of the biomaterials and regenerative medicine research as performed within research program "Tissue engineering and reconstructive surgery" of the Radboud University Nijmegen Medical Centre (RUNMC), within the research lines "Implants and biomaterials" and the RUNMC research program “Imaging”. The infrastructure offers an excellent environment for training and transfer of knowledge to recruited early-stage and experienced researchers. The research groups have access to or possesses all necessary equipment and facilities, including coating equipment, SEM and TEM facilities, cell culture facilities, animal research facilities with centralized small animal imaging facilities (micro-CT, animal MRI, animal PET/CT), soft and hard tissue animal models, chemical laboratories, histological laboratory, biochemical and molecular biological equipment, X-ray diffraction, surface analysis equipment, infrared equipment etc. The Laboratory for Experimental Urology (integral part of the department of Urology), the Department of Periodontology and Biomaterials, and the Department of Radiology all participate in the Nijmegen Centre for Molecular Life Sciences (NCMLS); which is a leading multidisciplinary research school within the domain of molecular mechanisms of disease and particularly in the fields of molecular medicine, cell biology and translational research. Research at Experimental Urology is focused on fundamental as well as applied aspects of soft tissue engineering (bladder, urethra) and oncology. Access to human material is possible as a result of close interactions with clinical staff members. The department has a long-standing interest in translational research. The group consist of a full professor, one associate professor, one assistant professor, postdoctoral fellows, 7 PhD students and 8 technicians. The Department of Periodontology and Biomaterials of the RUNMC is a large research group, currently consisting of a full professor, an associate professor, three assistant professors, 5 postdoctoral researchers, 25 PhD students, and 5 technicians. Projects focus on percutaneous implants, tissue compatibility of implant materials, permucosal oral implants (animal and clinical experiments), calcium phosphate-based ceramics, and bone and soft tissue engineering. Research is focused on fundamental as well as applied aspects of biomaterials used to replace damaged or lost hard and soft body tissues. The MR research group of the department of Radiology of RUNMC consists of one full Prof., 2 staff members, 6 PhD students, 3 senior technicians. The group has exceptional expertise in high resolution MR imaging, and diffusion, perfusion and metabolic imaging. Additionally, the group has ample experience in cell labeling with superparamagnetic particles of ironoxide (SPIO) for MR imaging and recently has made substantial progress in cellular labelling with 19F compounds.

Team members E. Oosterwijk, PhD, assoc. Prof.(20%), translational research P. Geutjes, PhD, postdoctoral fellow (20%), specialist biomaterials, bladder and ureter reconstruction in animals T. van Kuppevelt, PhD, assoc. prof (adv, specialist smart matrix development) W. Feitz, prof paediatric urology (adv), clinical implementation of scaffolds J.A. Jansen DDS PhD, specialized clinical implantologist (adv) X. F. Walboomers, PhD, associate professor, medical biologist and biomaterials specialist (10%) V. Cuijpers, BSc, imaging technician, µCT, ICAT, 3D scanning, virtual microscopy (30%) A. Heerschap, PhD, prof Experimental biomedical MR research (10%), specialized in high resolution MRI development T. Scheenen, PhD, Biophysicist, 7T MRI system (10%) M. van der Graaf, PhD, Biophysicist, MRS specialist (10%) A. Veltien, MS (10%) , expert in MR hardware, acquisition and processing M. van Uden (10%), MS, expert in MR hardware, acquisition and processing J. van Asten, MS (10%); expert in MR hardware, acquisition and processing

Publications de Vries IJ, Lesterhuis WJ, Barentsz JO, Verdijk P, van Krieken JH, Boerman OC, Oyen WJ, Bonenkamp JJ, Boezeman JB, Adema GJ, Bulte JW, Scheenen TW, Punt CJ, Heerschap A, Figdor CG. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol. 2005 Nov;23(11):1407-1413. Sitharaman B, Shi X, Walboomers XF, Liao H, Cuijpers V, Wilson LJ, Mikos AG, Jansen JA.In vivo biocompatibility of ultra-short single-walled carbon nanotube/biodegradable polymer nanocomposites for bone tissue engineering.Bone. 2008 Aug;43(2):362-70. S.T. Nillesen, P.J. Geutjes, R. Wismans, J. Schalkwijk, W.F. Daamen, T.H. van Kuppevelt, Increased angiogenesis and blood vessel maturation in acellular collagen-heparin scaffolds containing both FGF2 and VEGF. Biomaterials, 28(6) (2007).

Expertise The Polymer Chemistry Laboratory research unit at the Department of Materials Chemistry, at Uppsala University has significant expertise and full infrastructure for the development of new implantable materials. Research focuses on the development of materials for growth factor delivery for tissue regeneration, protein, drug and gene delivery as well as the synthesis of biodegradable polymers assembly for controlled structured materials and evaluation of functional properties. for in vivo use. This include synthesis, characterization, cell culture, protein lab, direct access to small and large animal facilities and access to patients in two major hospitals. The Polymer Chemistry Laboratory employs 3 staff scientists, 2 postdocs, 4 PhD students, 2 master students and 2 technicians. Uppsala University has today more than 40´000 students, has hosted 8 Nobel Laurates through the years and is ranked as No. 21 in Europe. It holds its strength in the life science area within an environment of pharmaceutical and medical device industry.

Expertise The Laboratory of Tissue Engineering is part of the Institute of Surgical Research and Hospital Management in the University Hospital of Basel and the Department of Biomedicine of the University of Basel. The laboratory for Tissue Engineering currently employs 3 MD, 3 staff scientists, 4 postdocs, 9 PhD students, 2 master students and 2 technicians. The team incorporates scientists from the biological and engineering fields as well as clinical staff thus allowing interdisciplinary work and transfer of knowledge. Tight connections with leading international chemical and pharmaceutical industries are in-place. The research focuses on mesenchymal cell differentiation, engineering of cartilage grafts and osteochondral composites, and design/implementation of tissue culture bioreactors for streamlined biomanufacturing, development of bioreactors for automated and controlled manufacturing of cartilage, bone and osteochondral grafts, based on autologous cells and 3D scaffolds. All required facilities for carrying out the research work are internally available, including: general molecular and cellular biology equipment, automated embedding and staining station for histology, fully certified animal facilities for small and large size animals, confocal microscope, closed bioreactor systems for cell isolation and expansion on 3D scaffolds, compression/perfusion bioreactors for tissue mechanical conditioning.

Expertise The Tissue Biology Research Unit (TBRU) is the experimental research laboratory of the Department of Surgery of the University Children's Hospital Zurich, Switzerland. The research unit focuses on the development of autologous dermo-epidermal skin substitutes (full thickness skin analogues) that can be used clinically to cover skin defects of any origin. Key expertise: the isolation, expansion and characterization of skin cells, the engineering of complex skin substitutes, monitoring (tissue homeostasis and self-renewing capacity) of skin substitutes in vitro and the generation of human capillaries and pre-vascularization of tissue substitutes in vitro. The Tissue Biology Research Unit was just provided with new and more laboratory space by the University of Zurich. The Unit provides an excellent infrastructure within the department and within the University of Zurich, with all necessary equipment available. PhD students will be included in a PhD program guided by the University. The research group currently consists of an associate Prof., 2 postdocs, 1 research assistant, 3 PhD students, 2 master students. The Research Division of the Department of Obstetrics has specialized in the development of biological therapies for hard-to-heal wounds such as skin ulcers, ischemic or infarcted heart and limbs, and the repair or prevention of fetal membrane rupture using Experimental Tissue Engineering. The research group currently consists of 2 PhD students, 4 postdocs, and 2 technicians. The research division is fully equipped for the work proposed and has constructed novel experimental platform available that permits sealing tests on human fetal membranes ex vivo. The infrastructure is fully equipped for state-of-the-art cell biology, molecular biology, and proteomics. Genomics studies are performed at the Functional Genomics Centre of the University of Zurich. Animal studies are performed at the Central Biological Laboratory.

Expertise Aap Biomaterials (total personnel 180) is global design and development leader in the field of biologic implants and biomaterials. Aap Implantate AG is an internationally-active and rapidly growing medical technology company active in the development, production and marketing of biomaterials and biomedical implants for medical indications related to trauma, orthopedic, spine, dental and medical esthetic applications. EMCM (part of Aap, located in Nijmegen, The Netherlands) is a centre of excellence in developing and manufacturing sterile medical implants and pharmaceutical specialties. Developed products by EMCM include bone cements, cement restrictors, cosmetic injectables, and a sterilization method for women. EMCM operates in its own classified rooms (over 1,500 square meters) for the manufacturing of medical products. In addition to its Berlin headquarters, the company has R&D and production subsidiaries in Dieburg and Obernburg near Frankfurt am Main. Aap provides essential technology input to make the purification process applicable for all biopolymers. Analytical input to assess and validate the process capabilities, small scale and large scale are available. Aap has extensive expertise in GMP / ISO13485 procedures, ISO9001:2000 and ISO13485 approved marketing and sales organization for medical devices, excellent track-record of marketing and sales of medical devices including partnership deals with big international pharmaceutical companies and device industries, and a very strong track record in getting production of devices approved by FDA and GMP authorities.

News and Events MultiTERM General Assembly and WorkshopsJanuary 2012 The 4th MultiTERM meeting was held at the Radboud University Nijmegen Medical Centre, The Netherlands on Monday January 9, 2012. The rest of the week was devoted to a workshop on imaging. MultiTERM in Parliament Magazine's MEP photo guide 2011October 2011 Information about the MultiTERM project was published on page 26 in the Parliament magazine's supplement MEP photo guide 2011, published on Monday, 26th September 2011 with the main issue of the Parliament Magazine. Copies of the guide were distributed to members of the European Parliament, the Commission as well as European Trade Associations and Public Affairs Consultancies in Brussels. Grant for MultiTERM fellowSeptember 2011Xia Yang (Uppsala University) received a grant from the organizers of the Summer school on Biomaterials and Regenerative Medicine (University of Trento), held on 19-23 September 2011, Riva del Garda, Trentino region, Italy. Xia gave an oral presentation at the Summer school on development of multifunctional HA-based carriers by “click” chemistry. Mid-term review and training courses/workshopJune 2011 The Mid Term Review of MultiTERM by the Research Executive Agency acting on behalf of the European Commission took place on May 30, 2011 at the Uppsala University, Sweden. The review was followed by courses on presentation skills and writing papers, and a workshop on composite matrices. MultiTERM General Assembly and Workshops October 2010 The 2nd MultiTERM meeting was held at the Radboud University Nijmegen Medical Centre, The Netherlands on Monday October 4, 2010. All fellows presented their research projects. The rest of the week was devoted to a workshop on bone tissue engineering and a workshop on production of biomaterials. Travel awards for MultiTERM fellows August 2010 Marta Kisiel, ESR fellow at Uppsala University, has been awarded a European Science Foundation Travel Grant to attend the 8th International Conference on Bone Morphogenetic Proteins in Leuven, Belgium from September 15-18, 2010. She will present her poster "The Local Treatment of Osteoporotic Bone: The effects of BMP-2 and hydrogel compound". Weilun Sun, ESR fellow at RUNMC, Nijmegen, has received a student travel award to attend the 16th International Conference of the International Society of Differentiation - From stem cells to organisms at Nara-Ken new public hall, Nara, Japan, November 15-18, 2010. At the conference, she will present her poster "Identification of Urothelial Stem Cells for Tissue Engineering". MultiTERM kick-off meeting March 2010 The MultiTERM kick-off meeting was held at the Radboud University Nijmegen Medical Centre, The Netherlands from March 29-31, 2010. Eleven fellows with their supervisors attended the meeting (two other fellows will start in May).

Links European program on Soft Tissue Engineering for Children (EuroSTEC) Tissue Engineering and Regenerative Medicine International Society (TERMIS) Marie Curie Actions Marie Curie Fellows Information Page TED talks on tissue engineering: Nina Tendon - Caring for engineered tissueTissue engineer and TED Fellow Nina Tandon is growing artificial hearts and bones. To do that, she needs new ways of caring for artificially grown cells -- techniques she's developed by the simple but powerful method of copying their natural environments.Posted July 2011 on TED. Anthony Atala on growing new organsAnthony Atala's state-of-the-art lab grows human organs -- from muscles to blood vessels to bladders, and more. At TEDMED, he shows footage of his bio-engineers working with some of its sci-fi gizmos, including an oven-like bioreactor (preheat to 98.6 F) and a machine that "prints" human tissue.Posted Jan 2010 on TED.