TENDON REGENERATION · Targeting Functional Tendon Regeneration Using a Loaded Biomimetic Scaffold. An Integrated Pan-European Approach

Targeting Functional Tendon Regeneration Using a Loaded Biomimetic Scaffold. An Integrated Pan-European Approach

A summary description of the project objectives Tendon Regeneration – Targeting Functional Tendon Regeneration Using a Loaded Biomimetic Scaffold: An Integrated Pan-European Approach, was an FP7 Marie Curie, Industry Academia Partnerships and Pathways funded award. Completed in August 2014, the project aimed at developing technology, which would enable functional regeneration of injured or degenerated tendons. The project team, comprised of three academic and three industry partners, effectively collaborated and harnessed complementary skills and knowhow in biomaterials and tissue engineering, in vitro and in vivo analyses, textile engineering and new product development for the development of a novel biomimetic (collagen/resilin-based) three-dimensional fibrous composite for functional tendon regeneration. The funding model allowed for staff secondments ensuring transfer of knowledge between industry and academic partners, while ensuring funded fellows’ career development through inspectoral experience and targeted training. In total twenty-two researchers were directly supported and 255 person months were completed over the four-year project. A description of the work performed since the beginning of the project The work programme was divided in four Work Packages, which are briefly described below: Work Package 1: Collagen and Resilin Production The National University of Ireland, Galway (NUI Galway) and Vornia Biomaterials (VN) extracted, purified and fully characterised atelo-collagen from BSE-free bovine Achilles tendons, suitable for biomedical applications. The Hebrew University of Jerusalem Israel (HUJI) and CollPlant (CP) joined forces to successfully express human recombinant resilin in E. coli. After appropriate optimisation and subsequent purification steps, human recombinant resilin of sufficient purity was produced. Work Package 2: Fibre fabrication, stabilisation and functionalisation Researches at NUI Galway, VN, HUJI, CP, Bolton University (BU) and North West Textile Network (NWTexNet) harmonically collaborated to develop a collagen and a collagen / resilin composite, which was optimally stabilised with various cross-linking methods (e.g. starPEG system, genipin, EDC/NHS) and effectively functionalised with various therapeutic and bioactive molecules, including hyaluronic acid, IL10 / decorin genes. Work Package 3: In vitro and in vivo evaluation of the fibrous composite Following production of the various scaffolds, extensive in vitro analysis was carried out at NUI Galway, VN, BU, CP and HUJI. Specifically, surface morphology was assessed with scanning electron microscopy. Differential scanning calorimetry was employed to assess thermal properties. Tensile testing was used to assed mechanical properties. The cytocompatibility of the produced scaffolds was assessed using human dermal fibroblasts, human tenocytes and rat tendon stem cells. The clinical relevance of the produced materials was assessed in a tendon preclinical model at HUJI. Work Package 4: Scaling up of prototype A collaborative effort between BU, NWTexNet, NUI Galway and VN resulted in a continuous, laboratory-scale, extrusion system, using principles from engineering and textile technologies. A description of the main results achieved so far, and the expected final results and their potential impact and use (including the socio-economic impact and the wider societal implications of the project so far). The Tendon Regeneration project represents a paradigm in maximum outputs per budget and time available. Specifically: Researcher Training: 21 researchers were trained in cutting edge research and development and equipped with appropriate knowledge from both academic and industry setting, increasing their career prospects. Technological: Collagen; resilin; composites of thereof; and functionalised scaffolds were developed. Further, methods to maintain tendon-derived cell phenotype in vitro were also developed. Continuous extrusion systems that facilitate scaling up and consequently commercialisation of fibrous composites were also developed. Scientific: The consortium has already published five papers in high impact factors journals, e.g., Trends in Biotechnology, Journal of Tissue Engineering and Regenerative Medicine. One further is under submission and ten in preparation. Results of this work were also presented in numerous Tier 1 international conferences and meetings, including, but not limited to Tissue Engineering and Regenerative Medicine Society, European Society for Biomaterials, Society for Biomaterials, Orthopaedic Research Society. Societal: The project has made significant progress towards development of functional three-dimensional scaffolds for tendon repair and regeneration, a clinical need with a mounting 200,000 new clinical cases worldwide. Having reached technology readiness level 4 within the project timeframe, we anticipate that with subsequent funding the developed technologies will reach clinical translation and commercialisation within 4-5 years. Please include also, as appropriate, diagrams or photographs illustrating and promoting the work of the project, the project logo and relevant contact details. The project logo has been included as an attachment. Project Coordinator: Dr Dimitrios I. Zeugolis Email: dimitrios.zeugolis@nuigalway.ie Project Manager: Dr Oonagh Dwane Email: oonagh.dwane@nuigalway.ie The address of the project public website should also be indicated, if applicable.

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