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• cell and developmental biology/regenerative medicine
• bioengineering/medical devices

• Surgery
• Ophthalmology

• Cardiology
• Dermatology
• Infectious diseases
• Neurology
• Orthopaedic surgery
• Otorhinolaryngology
• Pharmacology
• Vascular Medicine

Prof. Fergal O?Brien is a leading innovator in the development of advanced biomaterials for regenerative medicine. His research focuses on the development of natural polymer (such as collagen) scaffold-based therapeutics for tissue engineering with target applications in bone, cartilage, cardiovascular, ocular, respiratory and neural tissues. A major focus of ongoing research has been to functionalise these scaffolds for use as delivery systems for biomolecules with a particular interest in the delivery of nucleic acids (pDNA, siRNA and microRNA) to enhance their therapeutic potential. His group also focusses on the use of these scaffolds as advanced 3D pathophysiology in vitro systems for drug development and for studying cellular crosstalk in co-cultures and understanding disease states in cancer, angiogenesis, immunology and infection. In addition, he has a major interest in studying the response of living cells to mechanical stimuli (mechanobiology) and using biophysical stimuli (applied by bioreactors or controlled by scaffold stiffness) to regulate stem cell differentiation. A number of technologies from his lab have been patented resulting in the spin out in 2011 of a high potential start-up, SurgaColl Technologies. The first product from the group commercialised by SurgaColl, HydroxyColl, a collagen-hydroxyapatite bone graft substitute received regulatory approval (CE mark) in Nov. 2015 and is currently in clinical use. A second product, ChondroColl, a multi-layered scaffold for cartilage repair, is expected to receive regulatory approval in 2016. Human clinical studies are expected to commence in 2017.

The proposed project will utilise the clinical background of the PhD fellow in order to develop an advanced therapeutic for tissue regeneration or as a drug delivery platform for the treatment of cancer or infectious disease. The use of nanoparticles as vesicular systems for drug delivery is an important area of research for the development of improved therapies. The aim of this project is to develop functionalised collagen-based scaffolds for the delivery of nucleic acids using novel nanoparticle formulations which have recently been developed by researchers based in the RCSI Tissue Engineering Research Group and SFI-funded AMBER research centres. Depending on the background and interest of the PhD fellow, these gene-activated scaffolds will be used as platforms for tissue regeneration (for example in wound healing, cartilage repair or in ocular or neural applications) or to silence genes associated with cancer or infection. Alternatively, the scaffolds will have potential to act as physiologically-relevant 3D systems for disease modelling and for drug development and delivery.

The researcher will be primarily based in the Tissue Engineering Research Group and AMBER Centre at RCSI and will work closely with other members of a multidisciplinary project team including PIs, postdoctoral and postgraduate researchers within this research cluster.

Publications (5 most closely related to project):
1. Raftery, R; Walsh, D; Menc?a Casta?o, I; Heise, A; Duffy, GP; Cryan, SA; O'Brien, FJ. (2016) Delivering nucleic-acid based nanomedicines on biomaterial scaffolds for orthopaedic tissue repair: challenges, progress and future perspectives. Advanced Materials 2016 doi: 10.1002/adma.201505088.
2. Curtin, C; Tierney, EG; McSorley, K; Cryan, SA; Duffy, GP; O?Brien, FJ. (2015) Combinatorial gene therapy accelerates bone regeneration: non-viral dual delivery of VEGF and BMP2 in a collagen-nanohydroxyapatite scaffold. Adv. Healthcare Materials. 28;4(2):223-7 doi/10.1002/adhm.201400397
3. Tierney, EG; Duffy, GP; Hibbitts, AJ; Cryan, SA; O?Brien, FJ. (2012) The development of non-viral gene-activated matrices for bone regeneration using polyethyleneimine (PEI) and collagen-based scaffolds. Journal of Controlled Release 158: 304?311
4. Mencia Casta?o, I; Curtin, CM; Duffy, GP; O?Brien, FJ. (2016) Next generation bone tissue engineering: non-viral miR-133a inhibition using collagen-nanohydroxyapatite scaffolds rapidly enhances osteogenesis. Scientific Reports, 6, 27941; doi: 10.1038/srep27941
5. Curtin, C; Lyons, F; Cunniffe, GM; Bessho, K; Duffy, GP; O?Brien, FJ. (2012) Innovative collagen nano-hydroxyapatite based scaffolds offer a highly efficient non-viral gene delivery platform for stem cell-mediated bone repair. Advanced Materials 24(6):749-54. doi/10.1002/adma.201103828