Final Report Summary - COLLREGEN (Collagen scaffolds for bone regeneration: applied biomaterials, bioreactor and stem cell technology) Collectively, this research programme has been superbly successful and, centred on the collagen-based materials used in Prof. O’Brien’s laboratory, it has developed new insight and technologies in areas including research in biomaterials science, gene therapy, stem cell biology, bioengineering and clinical medicine. Specific outputs from the different themes are as follows. Theme 1: Osteoinductive and angiogenic smart scaffolds for bone tissue regenerationThe major outcome from this theme is that the collagen-based scaffolds developed within the laboratory have the ability to act as gene activated matrices (GAMs). We demonstrated that these scaffolds have the potential to act as platforms for the delivery of angiogenic genes and osteogenic genes both alone and in combination. Additionally, this was demonstrated using two different non-viral gene delivery vectors demonstrating the successful development of smart scaffolds for bone regeneration. The platform system established to incorporate and control the release of these plasmids has also now been applied to both siRNA and microRNA targets with significant success. Further exploitation of this concept is currently being explored with follow on research grants including an ERC Proof of Concept grant in the latter area. Growth factor-eluting scaffolds were also developed by incorporating BMP-2 and VEGF loaded polymeric microparticles into collagen-hydroxyapatite scaffolds. BMP-2/VEGF release kinetics were modulated to the desired levels by changing the amount and composition of the microparticles while retaining bioactivity throughout the process. The platform system established to incorporate and control the release of these growth factors has significant potential for a variety of applications some of which are currently being explored with follow on research grants (including nerve regeneration and osteomyelitis). Furthermore, we also showed that by incorporating hypoxia-mimicking cobalt bioactive glass into the scaffold, we could mimic the effect of having growth factors present resulting in an innovative growth-factor free biomaterial that can promote vascularisation and bone repair. Theme 2: Scaffold and stem cell therapies for bone tissue regenerationThe work performed on this theme was based on the use of an in vitro tissue engineering approach to induce neovascularisation and bone formation in collagen-based scaffolds using two cell sources. The results provided new information on the role of two types of stem cells (human bone-marrow and amniotic fluid derived stem cellss) in regulating the process of vasculogenesis and the crosstalk that exists between different cells types. In addition the research led to the development of two new novel scaffolds for vascular tissue engineering, consisting of collagen and elastin co-polymer tubular structure, and heart valve repair, consisting of collagen and fibrin co-polymer engineered into a heart valve shaped structure. Theme 3: Bone tissue engineering using a novel flow perfusion bioreactorWork undertaken in this theme has shown that computational modelling of bioreactor systems is capable of predicting experimentally observed outcomes and is able to provide insight as to the potential mechanisms driving these outcomes when the experimental techniques available are not capable of providing further understanding. Additionally, we identified key genes that regulate the differentiation of progenitor cells into bone cells when mechanical stimuli is applied and how hypoxia affects the ability of progenitor cells from different sources to form tubules. These key genes form the basis of new clinical targets to enhance osteogenesis and angiogenesis and their therapeutic potential is currently being explored with follow on research grants.Theme 4: In vivo bone repair using engineered bone and smart scaffoldsUsing suitable in vivo models, Theme 4 successfully validated the in vitro results from Themes 1&2 and demonstrated the potential of the different systems developed to promote vascularisation and bone healing.To summarise some of the quantitative output from the project. 8 researchers received PhDs from the research. 38 scientific peer-reviewed papers were published in leading journals such as Advanced Materials (IF: 17.5),Materials Today (IF: 14), Biomaterials (IF: 8.5) Journal of Controlled Release (IF: 7.5) Acta Biomaterialia, Advanced Healthcare Materials and Tissue Engineering. A number of others will arise in coming months. Over 58 awards or accomplishments were received by Prof. O'Brien and his team and numerous follow on grants were awarded including major initiatives such as the €58million AMBER Centre of which Prof. O'Brien is Deputy Director. The research has been covered extensively by the media and we have provided extensive opportunities for the next generation of researchers in form of undergraduates, primary school and secondary school students and their teachers) to engage with us on the project. Prof. O'Brien and his team believe it has been an incredibly successful project and are proud to worked with the ERC in delivering this programme.
