Final Report Summary - SKELGEN (Establishment of a cross continent consortium for enhancing regenerative medicine in skeletal tissues) 'SkelGEN’ is a cross continental consortium, which was funded by the EU FP7 International Research Staff Exchange Scheme (FP7-PEOPLE-2012-IRSES: No. 318553). It brings together leading research institutions across disciplines in biology/engineering/computational modelling/orthopaedic research in the EU (UK, the Netherlands, Portugal) partnered with complementary experts in New Zealand. It was initiated on 1st December 2012 for four years (till 30th Nov 2016) with 8 EU beneficiaries (University of Leeds, University of Southampton, University of Oxford, University of Loughborough, University of Manchester, University of Minho, Polytechnic Institute of Leiria, and University Medical Centre of Utrecht) and 2 New Zealand partners (University of Auckland and University of Otago). (More information and the links to the EU beneficiaries’ and NZ partners’ websites can be found at: http://medhealth.leeds.ac.uk/news/article/1105/skelgen or http://cordis.europa.eu/project/rcn/109152_en.html).The mission of SkelGEN was to achieve coordinated and planned institutional research collaborations to ultimately establish a larger collaborative research project to specifically develop and apply platform technologies for skeletal repair exemplified through the development of an osteochondral (bone/cartilage) constructs. The 2 New Zealand partners received financial support from the Royal Society of New Zealand that made it possible for all partners to participate in this excellent scheme. SkelGEN led to truly encouraging collaborative work for exchanging knowledge, educating scientists and students (early-stage researchers: ESRs) as well as enabling cross-continental collaborations in leading international research in skeletal regenerative medicine and potential development of novel medical devices in both New Zealand and EU countries. This cross-continental consortium had four distinct but inter-related working packages (WPs) for the joint exchange programme to generate: appropriate stem cells (WP1: lead by USOTON), biocompatible biomaterial scaffolds (led by UOTAGO), their interaction and development through experimentally informed computational modelling (led by USOTON), and finally the evaluation of osteochondral and/or bone-ligament constructs using standardised protocols and in various small/large animal models (led by UNIVLEEDS) for proof-of-concept of clinical efficacy. Some beneficiaries/partners were involved in more than one WP(s).All of the beneficiaries/partners had extensive experience in hosting international visiting researchers. Each partner had a well-staffed Research Office or International Office that provided practical support and help so that visitors were quickly integrated into the host community and wider society. Visitors were full members of host institutions during the period of their stay and were provided with library, computer, internet access, and workspace/bench facilities. All exchanges involved hands-on training and mentoring regarding its organisational structure, and research practices and techniques. The visitors also communicated with home supervisor(s) via emails or teleconferences to update the training and research progress of the secondments. After the kick off teleconference in early Dec 2012, ‘SkelGEN’ held total four ‘annual progress meetings and workshops’ in UNIVLEEDS (Oct 2013), UoA (Dec 2014), UMINHO (Sept 2015) and UOTAGO (Aug 2016). In between, teleconferences have been held to provide opportunities for discussing the progress and achievement on secondments, collaborative projects, activities, any issues encountered, actions to be taken, as well as future exchange plan (secondments) and forthcoming events. In addition, the beneficiaries/partners have also organised and chaired a dedicated ‘SkelGEN symposium’ at the Tissue Engineering and Regenerative Medicine International Society (TERMIS) World Congress, Boston (Sept. 2015), and the ‘Stem Cells and Regenerative Medicine Satellite Symposium’ Queenstown Molecular Biology Conference, New Zealand (August 2016). Furthermore, other symposia/workshops/seminars at UoA (2013, 2014), UOTAGO (2014, 2016), UMAN (2014, 2015), PILERIA (2015) were organized for dissemination of the research findings from SkelGEN consortium.During the project period, a total of 38 personnel (including 17 ERs and 21 ESRs) and 54 trips were made from EU beneficiaries to NZ partners (achieving a total of 76.6 full-time equivalent months of secondments; 95.75% of initial proposed target of 80 months). Databases for WP1, WP2 and WP4 regarding to available stem cell sources/research facilities, existing biomaterial scaffolds, standardised protocols, status of ethical situations have been completed for sharing between the partners and monitoring of progress towards objectives and deliverables. Through the exchange of ESRs and ERs between EU beneficiaries and NZ partners, new projects/research directions have been identified. Over the last four years, the PIs and seconded researchers of SkelGEN EU beneficiaries and NZ partners have contributed a total of 38 book/book chapters, 380 papers (14 manuscripts were submitted or in press) and 119 keynote/invited talks and 147 presentations, which were related to the SkelGEN project’s remit. 10 patents were filed by the beneficiaries and/or partners during the project period (7 patents were published). Total 81 research grant proposals have been submitted by the EU beneficiaries and NZ partners (57 successful and 8 pending). The PIs and/or ESRs won total 23 prizes/honours during the project period. In a number of cases, results from the secondments lead to joint presentations at national/international conferences, publications, and new grant applications. Since the most of secondments occurred in years 3 and 4, more joint papers, presentations and grant applications are expected in 2017/2018 or beyond. In particular, SkelGEN consortium have submitted two joint ITN grant proposals to EC: UMCU/USOTON/UOTAGO; PILEIRIA/UNIVLEEDS (pending), which show the evidence of establishment of sustainable institutional linkages via SkelGEN project. If successful, these applications will enhance the sustainability of the SkelGEN project. Since the most of secondments occurred in years 3 and 4, more joint papers, presentations and grant applications are anticipated for 2017/2018.During the project period, the SkelGEN consortium have been working on four distinct but interrelated working packages. In WP1, the protocols for isolation, characterisation and expansion of skeletal stem cells from different sources have been standardised and shared; The understanding of cell growth and nutrient modelling (WP3) as well as the use of stem cells in large animal (WP4) and clinical setting have been enhanced. In WP2, the consortium has developed several bio-manufacturing platforms for design and production of tissue-specific scaffolds (e.g. osteochondral constructs with optimised architecture and mechanical properties) for delivery of growth factors and controlling stem cell fate for skeletal tissue engineering. The links with orthopaedic surgeons and industry have been established for scale up towards clinical translation. In WP3, computational models have been developed for integrated understanding of stem cell behaviour and tissue regeneration in porous scaffold structures as well as defining physiological boundary condition for testing scaffold design. In WP4, the consortium has standardised the protocols for visualising scaffold topology, mechanical evaluation and immunogenicity testing, as well as in vitro/in vivo evaluation of biomaterial scaffolds; different bioreactors have also been optimised and shared for assessing cells grown within the scaffold structures. In conclusion, SkelGEN has successfully established a cross continental consortium between EU and New Zealand researchers to establish multidisciplinary research platforms for 1) training the ESRs to become the next generation of researchers in skeletal tissue repair/regeneration; 2) initiated/coordinated institutional research collaborations to ultimately establish larger scale collaborative research projects for skeletal tissue repair and regeneration (via four work packages) for patient benefit; 3) facilitated industrial linkages and commercialisation/knowledge transfer; 4) promoted the engagement of research scientists with clinicians at the early stage of R&D for potential route to clinical translation, which has huge social and economic impact for the community.
