OSTASKILLS

Marie Curie research training project on Osteoarthritis




Prof. Dr. Marcel Karperien / Twente University / The Netherlands

“Marcel Karperien is a professor in Developmental BioEngineering (www.utwente.nl/tnw/dbe) at the University of Twente in the Netherlands. His work is multidisciplinary in nature, combining expertise in biology, chemistry, physics and typical engineering disciplines and is focused on developing and implementing technology inspired solutions for important biomedical challenges such as osteoarthritis and type I diabetes. Current research in his group focusses on the development of injectable hydrogel platforms that could serve as fillers of cartilage defects and could be used as so-called bioinks for printing of living tissues, the use of the variable domain of single chain, heavy chain only antibodies (VHH) as intra-articular injection therapy and the engineering of a so-called isogenic Joint-on-a-Chip.

University Twente is an entrepreneurial and research-oriented university, standing for “high tech with a human touch”. At the UT, over 3000 scientists and professionals conduct pioneering research and offer impactful, innovative and inspiring education to about 10,000 students. Research institutes combine scientific excellence with a sharp eye for economic and societal impact. Institutes are highly successful in generating spin-off businesses (over 50 new companies annually). Considering the participation in EU funding initiatives, UT researchers have been involved in over 220 FP7-projects and in 148 Horizon2020-projects to date. Since 2014, the UT has been participating in 26 MSCA-ITN and 5 MSCA-RISE projects, including FRESCOatCNAP (MSCA-COFUND 2016), GLASNOST (MSCA-IF-2017) and LASER4FUN (MSCA-ITN-2015).

PhD students appointed at University of Twente will enrol in the Twente Graduate School (TGS) and are offered various courses for completing their training to become an independent researcher. A complete list of courses offered by the University of Twente (of which many are applicable for PhD students) can be found at the following website: https://www.utwente.nl/en/ctd/courses/. They deal with science, language (English scientific writing skills, preparing posters for conferences and presentation skills), personal effectiveness but also with career development. PhD students can also follow specific master courses. Relevant for this doctoral training programme are several master courses offered in biomedical engineering. The valorisation unit of the University of Twente offers dedicated training courses on intellectual properties, setting an own business which are also accessible for PhD students. The mission of TGS is to train and educate excellent researchers and to present and promote excellent research and design via doctoral programmes. The doctoral candidates are trained to prove their competence by means of a doctoral thesis.  With this mission, TGS aims to improve the quality of research and education, to accentuate UT's identity and profile and to differentiate and individualise the specific doctoral programmes and services for its participants.



Prof. Dr. Tim Welting / Maastricht University / The Netherlands

Tim Welting is professor at the department of orthopedic surgery of MUMC+ and an expert in molecular cartilage biology. He is head of the Laboratory for Experimental Orthopedics and is principal investigator and group leader of the Molecular Cartilage Biology research group. He recieved his PhD in biochemistry from the Radboud University Nijmegen in 2007.

The clinic of the Department of Orthopaedic Surgery is a Top Referral clinic for amongst others OA and cartilage repair surgery, and for many decades it has been our mission to provide innovation in orthopaedic health care through translating basic science towards meaningful clinical applications. We are leading the Dutch joint preservation clinics network. We approach our clinical orthopaedic challenges through basic molecular and preclinical research in our Laboratory for Experimental Orthopaedics, a ReumaNL Research Centre of Excellence. We are working on focal cartilage defects and attenuation of the progression of OA with a research team of more than 20 skilled experts bridging and connecting basic chondrocyte molecular biology with orthopaedic medical engineering. We have committed our research activities towards the development of autologous biological and artificial chondro-compatible implants for focal cartilage defects and towards the identification of osteoarthritis disease-modifying drugs (peptides in particular). Pre-clinical animal models for cartilage defects and OA are fully operational and lined-up with advanced high-resolution MR imaging for follow-up of treatment efficacy. Together with our growing (OA) joint tissue biobank, in-house orthopaedic clinical trial bureau to initiate and coordinate (first-in-man) clinical trials, and a campus that actively supports and propels valorisation activities, we are in a unique environment to enable the translation of science products towards meaningful clinical applications. In OSTASKILLS, UM offers specific training in (OA) chondrocyte and cartilage molecular biology; the design of drug screening approaches for OA; a variety of preclinical animal models for OA, cartilage defects, cartilage regeneration, and high resolution MR imaging, functional, biomolecular and histological follow-up; and clinical study design/first-in-man clinical studies for joint preservative new treatments in GCP-trained experienced orthopaedic clinical trial centre. UM has a solid track record of European training programmes: PersonalizeAF (MSCA-ITN-2019), MARCIUS, SINERGIA (MSCA-ITN-2019), THERADNET (MSCA-ITN-2019) and INSPIRE.



Prof. Dr. Andrea Barbero /University Hospital Basel / Switzerland


The common denominator of the research projects performed in the Cartilage Engineering Group (Prof. Dr. Andrea Barbero) is related to the establishment of three-dimensional culture systems, combining interdisciplinary efforts in cell biology, engineered technologies and materials science. These systems are used as model to investigate fundamental aspects of tissue (mainly cartilage) development, and as grafts to induce tissue regeneration.
Prof. Barbero`s group demonstrated that adult human nasal chondrocytes (NCs) display a large degree of plasticity and unique regenerative properties. Two phase I clinical trials at the University Hospital Basel demonstrating that engineered grafts based of nasal chondrocytes can be safely used for the treatment of nasal and articular cartilage. A phase II clinical study is now ongoing to assess the efficacy of such experimental procedure.
Currently, the potential of NCs for intervertebral disc (IVD) repair is being explored.

The multidisciplinary group of the Laboratory of Tissue Engineering includes biologists, engineers and clinical staff, has a wide network of cooperation with international biotech industries and academic institutes, and is funded through public, private or foundation grants, acquired on a competitive basis. The core competence of the group lies in development of 3D cell culture models as well as in the engineering of cellular grafts to repair cartilage and bone tissues. As part of UNIBAS close interactions between the lab and the clinic allow for obtaining biopsies of human tissues, after patient informed consent as well as the conduction of clinical trials. The group established a streamlined automated manufacturing of these implants in perfusion-based bioreactor systems. After establishing a GMP-compliant quality management system, several clinical phase I and II trials have been conducted, translating the findings of the lab from bench to bedside. An international multicentre phase II study within the BIO-CHIP project (H2020 681103), is currently ongoing with 108 patients in 5 clinical centres treated with tissue engineered cartilage grafts for repair of focal cartilage lesions (about 2/3 of the patients enrolled). The Clinical Trial Unit (CTU) of the University Hospital Basel offers support for clinical trials.

The OSTASKILLS training plan foresees access to 1) hands-on training experience, 2) clinical data and theoretical training on biological systems provided by clinical-oriented partners (collaborators). The PhD candidate will validate the performance of own development complying with regulatory requirements of DDP. UNIBAS provides strong research supervision and intensive training in material sciences, biomaterial/biological integrated research design, medical device manufacturing. UNIBAS is a world leader in surgical training, where the doctoral candidate will collect experience, and deepen knowledge in the application of 3D-printed materials and their translation into the clinic. The candidates will be trained on in vitro and ex vivo studies, using chondrocytes and mesenchymal stem cells for example, and the use of specifically design bioreactors allowing control over the tissue environment.

UNIBAS comprises state-of-the-art facilities for the cell culture, cytofluorimetric activities (FACS cell sorting instrument), biochemistry, histology, animal facilities (mice, rats and rabbits). Furthermore, also in EU context there a vast experience in trainings of ESR’s, for example with MSCA-ITN-2019: “Advanced technologies for drug discovery and precision medicine: in vitro modelling human physiology and disease” and EU-Horizon 2020: “From Epigenetics of Cranial Neural Crest Plasticity to Intervertebral Disc Regeneration”.

 


Prof. Dr. Martin Stoddart / AO Research Institute / Switzerland

Prof Martin Stoddart became Program leader of the newly renamed Regenerative Orthopaedics Program within the ARI in 2020. He also is Focus area Leader for the Progenitor cell biology and mechanoregulation, and Bone Biology Focus areas. Prof Stoddart represents ARI at the AOCMF R&D Commision

He completed his bachelor studies in Biology at the University of Aberystwyth in 1995. He then spent a year in Davos at AO Research Institute Davos where he completed his M Phil in Cartilage Biology. Between 1996-2000 he completed his docotral thesis at the University of Nottingham in the field of Cancer Angiogenesis. He then returned to Switzerland to work in the Lavoratory for Experimental Cartilage Research in Zürich, initially as a Post Doc and between 2003-2005 as Group Head. During that time, he also took a six-month sabbatical at the Centre for Molecular Orthopaedics, Harvard Medical School, Brigham and Woman Hospital, Boston, to learn viral gene transfer techniques. In 2005 he returned to AO Research Institue Davos, where he became Principal Scientist and Docus Area Leader in 2009. He is a lecturer at the ETH Zürich and in 2015 he was awarded Professorship from the Medical Faculty of the Albert-Ludwigs University, Freiburg, Germany. In 2016 he was awarded an Honorary Professorship at the Institute for Science & Technology in Medicine University of Keele, UK. He is a fellow of th eRoyal Society of Biology and a fellow member of the International Cartilage Regeneration & Joint preservation Sociey. In 2020 he recieved the TERMIS-EU Mid-Term Career Award.

ARI is the research arm of the AO Foundation (AOF) which is the biggest trauma and orthopaedic network worldwide and one of the biggest medical networks at global scale. ARI has long-standing experience in musculoskeletal regeneration. In particular, the Regenerative Orthopaedics Program (RO) develops biological and biomaterials (e.g. scaffolds, bio inks) approaches addressing pathologies of the musculoskeletal system, with a  particular focus on bone and cartilage tissues and use of ex-vivo bioreactors, with over 25 years of experience in translating bone repair strategies in trauma and disorders of the musculoskeletal system. As part of its mission, research and technology transfer at ARI is realized through a cooperation network with many industrial partners. ARI trainings are unique and innovative, as no similar research institute can currently offer such a training programme globally. ARI will significantly contribute to the research and training programme by providing strong research supervision and intensive training in human MSC biology, human donor cell variation, chondrogenesis, mechanobiology and bioreactors. ARI is a world leader institute in surgical training, ARI will train in the application of 3D-printed materials and their translation into the clinic. ARI will also train on in vitro and ex vivo studies, using mesenchymal stem cells for example, and the use of specifically design bioreactors allowing control over the tissue environment (e.g. mechanical). ARI comprises state of the art facilities for 2D and 3D cell culture (comprising a FACS cell sorting instrument), microbiology, histology, mechanical testing, medical imaging, tools shop and chemical synthesis laboratories. In addition, ARI has state-of-the-art GLP/AAALAC-accredited veterinary facilities and can provide training in ethical animal model choice. ARI supervisors are associated with quality graduate schools, with procedures in place that allow for the recruitment of doctoral candidates from diverse educational backgrounds. ARI has a long-lasting track record of training programmes: BIOBONE-FP7-PEOPLE-2011-ITN, TargetCaRe-H2020-MSCA-ITN-2014, PREMUROSA-H2020-MSCA-ITN-2019, CATHAGO H2020-MSCA-ITN-2020. 


 

Prof. Dr. Denitsa Docheva /Julius-Maximilians-University of Wuerzburg / Germany

Denitsa Docheva is the Chair of the Department of Musculoskeletal Tissue Regeneration at the Orthopaedic Hospital König-Ludwig-Haus & the Julius-Maximilians-University of Wuerzburg.

Denitsa graduated with two parallel Master Degrees (Biology and Chemistry) from the University of Plovdiv, Bulgaria. Afterwards Denitsa obtained a PhD fellowship at the Max-Planck-Institute of Biochemistry, Martinsried, Germany and graduated in 2005. Then she moved to the Department of Trauma Surgery, Ludwig-Maximilians-University (LMU) in Munich, Germany where she established the Tendon Research Group. In 2012, Denitsa completed her habilitation in Experimental Surgery at the LMU. 2016 to 2021, she was Professor and Research Director at the Department of Trauma Surgery, University of Regensburg, Germany. In October 2021, she became Professor and Chair of the Department of Musculoskeletal Tissue Regeneration, University of Wuerzburg, Germany. She has published more than 100 articles and has won multiple grants. She is participating in several EU consortia (MATEGRA, ACHILLES, MEFISTO, OSTEOMET and OSTASKILLS). She has supervised more than 50 research fellows. She has given numerous invited lectures and communications at conferences. She is a reviewer for prestigious biomedical journals and since 2020, Scientific Editor for the eCM Journal. 2018-2020, she was the President of the European Orthopaedic Research Society (EORS). Currently, she is the EORS Past-President as well as a member of the steering committee of the International Combined ORS (ICORS).
Denitsa’s research is focusing on three main tracks: i) functions of tissue specific stem/progenitor cells, ii) mechanisms of tissue aging and degeneration, and iii) strategies promoting tissue repair and regeneration.
She is renowned expert on tendons and ligaments. While at the University Clinic of Regensburg, Denitsa collaborated intensively with Prof. Dr. Peter Angele, a distinguished clinical expert and OA scientist, in the area of cartilage, meniscus and OA. Specifically, in the OSTASKILLS consortium, we will aim to decipher: i) the response of human chondrocytes derived from healthy, trauma and early OA cartilage to various stimuli, this will be carried out in a tight collaboration with consortium partners and Prof. Angele; and ii) the molecular control of chondrogenic-fibrogenic switch during OA with potential involvement of tenogenic/ligamentogenic factors.
The University of Wuerzburg offers a high reputation as one of the leading national and international institutions for medical and basic research, as well as student education. The Julius-Maximilians-University (JMU), founded in 1402, today is a scientific home of approx. 28.000 students. Wuerzburg is aalso famous orthopaedic location with strong traditions since 1816 when the visionary Johann G. Heine established the first orthopaedic centre in Germany. 100 years later in 1916, the last Bavarian King Ludwig III gave the name of the Orthopaedic Hospital König-Ludwig-Haus. The Department of Musculoskeletal Tissue Regeneration is located at the IGZ Science Park and has fully equipped research laboratories and established cutting-edge-technologies, thus offering excellent work environment.


Ass. Prof. Dr. Paul Bourgine / Lund University / Sweden

Paul currently holds an assistant professor position at the University of Lund (Sweden), where he leads the Cell, Tissue & Organ engineering laboratory (www.bourginelab.com). His research aims at studying Bone as an organ system, understanding from a fundamental perspective how its constitutive tissues (bone, cartilage, marrow) form, interact and regenerate. By exploiting innovative in vitro/in vivo models of bone formation, he ambitions to compile human specific knowledge helping the design of regenerative therapies. One of the group favorite approaches consists in using death-inducible human cell lines as factory units to produce molecularly customized biological tissues, subsequently decellularized for skeletal repair. From bone, Paul´s interest extended to the hematopoietic system where the lab intends to understand the function of human mesenchymal cells in supporting blood stem cell renewal and differentiation.

Paul studied Biotechnology at the Ecole Superieure de Biotechnologie de Strasbourg, a European school joint venture of the universities of Freiburg, Strasbourg, Basel and Karlsruhe. He obtained his engineering diploma in 2010 after a stay at the Ragon Institute of Harvard, MIT and MGH (Boston, USA). Paul subsequently moved to Switzerland and received his Ph.D in Cell Biology from the University of Basel in 2013. After a three years post-doc at the Biosystem department of the ETH-Zürich, he opened his lab in 2018 at the faculty of medicine in Lund, embedded within the Stem Cell Centre and the Wallenberg Centre of Molecular medicine framework.

In the past 3 years, Paul has secured over 5M euros in funding as principal investigator, through prestigious national (e.g. Swedish Research foundation starting grant) and international calls (e.g. ERC Starting grant). Paul´s group has published in highly ranked journals including Advanced Materials, PNAS, Cell Stem Cell, Advanced Functional Materials, Trends in Biotechnology, Blood and his strongly connected to the TERMIS, ISSCR and ISEH societies. His research is at the crossroad between tissue/organ engineering and stem cell technologies, exploiting state-of-the-art technologies such as personalized engineering of human bone organs in mice, 3D quantitative microscopy, single cell transcriptomics, and 3D-printing of custom bioreactor system.  

Lund University is one of the biggest campuses worldwide, hosting over 44´000 students. The laboratory is located at the Biomedical Center, where ~100 research groups collaborate on various pre-clinical and clinical projects. The presence of core facilities such as Crisp/Cas9, cloning & virus production, animals, advanced microscopy, flow cytometry, embryonic and induced pluripotent stem cells and bioinformatic offer am ideal research ground for cutting-edge research.