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3D tissue engineering-based model of craniosynostosis for identifying potential therapeutic targets that might enhance bone repair.

About This PhD Project

Project Description

Craniosynostosis (CS) is a bone developmental condition that affects 1 in 2000 children worldwide. Children suffering with CS have premature fusion (bone formation) of the skull sutures, which restricts brain growth and may cause severe brain damage. The only currently available treatment is cranial vault remodelling (CVR) which is a highly complicated surgical procedure with significant potential risks involving the remodelling of the skull. However, due to skull re-fusion these children frequently undergo additional surgeries, highlighting the need for a better understanding of the mechanisms that accelerate bone formation in CS in order to potentially improve current therapeutic strategies. Nonsyndromic CS –primarily associated with micro environmental alterations- is the most common type of CS. However, the lack of appropriate research models for this form of CS, limits the understanding of sutures that behave pathologically.

Working with AMBER, the SFI Research Centre for advanced materials and bioengineering and industry and clinical partners, the RCSI Tissue Engineering Research Group (TERG) have driven considerable successes in the area of advanced biomaterials for bone tissue repair- translating novel biomaterials from the lab to the clinic. Using these biomaterials, and working with Mr. Dylan Murray, Consultant Craniofacial, Plastic & Reconstructive Surgeon at the National Paediatric Craniofacial Centre, Children’s Health Ireland at Temple Street, we have started to develop a tissue engineering (TE)-based 3D in vitro CS model that emulates the biophysical features of the skull sutures in order to identify the molecular pathways that promote suture fusion in Non-syndromic CS. Building on this research, in this project we will control suture fate in the CS model by utilising activators and/or inhibitors of the specific pathways identified. By using this approach we propose to identify potential targets to control prematurely fusing sutures. Therefore, we propose the use of a TE-based model built with cells from CS patients not only will emulate the native-tissue features better than 2D systems or in vivo animal models but will also empower us to improve current therapies by identifying the molecular pathways that control the pathology of the disease which might be used in a broader context for accelerating bone healing in complex bone fractures generally.

In this project, the student will be based in the RCSI TERG, the 2017 Irish Research Lab of the Year, and will work closely with Mr. Murray’s team. This will provide a unique opportunity for the student in terms of clinical engagement. The student will receive training in the areas of cell & molecular biology as well as biomaterial fabrication and characterization of the mechanical and biological response of the novel materials. S/he will attend TERG group meetings which take place weekly and will thus have the benefit of support from researchers from a diverse range of backgrounds, including materials science, engineering, pharmacy and the biological sciences in addition to clinical medicine. All necessary equipment and facilities required to complete the project as described are in place in our labs already.

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