Dimitrios Tsiapalis, Alessandro Dei, Dominika Berdecka, Andrea Rampin and Adrian Djalali Cuevas established protocols for the isolation, characterisation and culture of cells. They experimented with culture media to encourage tissue formation. Alessandro Dei developed a tendon-specific culture medium which can culture tendon cells and induce stem cells to develop into tendon-like tissues. Adrian Djalali Cuevas conducted an in-depth study of TDC proteins which may make the characterization of tendon cells possible for the first time. Giulia Sivelli progressed knowledge on treatment strategies for tendon inflammation. Traditionally, cell culture takes place on smooth, rigid culture plastics. Sofia Ribeiro developed biodegradable films of varying stiffness and topography which direct stem cell differentiation into tendon-type cells. Ignacio Sallent produced collagen-based substrates for cell culture which maintain topographical features, imitating the cells natural environment. Eugenia Pugliese engineered intricate multi-layered collagen scaffolds for complex tendon tissues. Steven Vermeulen identified the optimal topographies for the maintenance of tendon cell culture. Andrea de Pieri used a temperature-responsive polymer as a cell scaffold which is dissolved once a tissue of implantable size is produced. This allows tissue detachment from the culture surface; a feat which is not easily achieved. Aysegul Dede-Eren developed a protocol to remove cells from tendon tissue and use the resulting scaffold as a basis for tendon tissue engineering. Dimitrios Tsiapalis and Adrian Djalali Cuevas assessed fibrous constructs that closely imitate native tendon architecture. Dimitrios Tsiapalis, Andrea Rampin and Sergio Garnica Galvez investigated the use of macromolecules in the culture media seeking to increase the rate at which tissue is laid down. They identified molecules that support the tendon-specific culture of TDCs, BMSCs and ADSCs. These molecules crowd the culture space, driving cells to deposit more extracellular matrix; the structure which supports cells in the body. They successfully increased the amount of matrix laid down, as well as the rate at which the tissue forms, overcoming two bottlenecks to tissue culture. Tissue culture using a mechanical bioreactor or oxygen tension chambers was investigated by Dimitrios Tsiapalis, Ignacio Sallent and Salome Guillaumin. The bioreactor was used to apply mechanical forces to the cultures. This is important for tendon tissues which are load-bearing and subject to significant forces. Optimal mechanical stimulation for tendon work was identified as well as optimal oxygen tension. RVC developed a preclinical study for research outputs using an equine model. For the first time, equine stem cells cultured with tendon-specific topographies were implanted in an equine patient. 3D tissue implants developed using the temperature-responsive polymer, MMC and ADSCs, were implanted at NUIG by Andrea De Pieri demonstrating superior preclinical outcomes to control groups. 15 ESRs have received interdisciplinary training and experience in all aspects of Advanced Therapy Medicinal Product (ATMP) development with input from academic, industry and clinical partners. Over 100 conference presentations and over 30 journal publications have resulted so far. Exploitation plans have been prepared for cell and cell-culture products, scaffolds and tissue implants. Andrea de Pieri has co-drafted an IDF on cell sheet engineering which is being considered for patent application. Alessandro Dei developed the serum-free media for tendon applications. Sofia Ribeiro and Steven Vermeulen received conference awards. Public engagement activity included school visits (Dominika Berdecka, Sofia Ribeiro, Andrea de Pieri, Eugenia Pugliese, Ignacio Sallent, Salome Guillaumin) science fairs and events (Alessandro Dei, Steven Vermeulen, Giulia Sivelli) newspaper articles (Andrea Rampin) and a film documentary broadcast on National Television and at the Galway Film Festival.
