PhD Studentship Developing a 3D organotypical model to assess skin and gum penetrating implant soft tissue outcomes and implant device development



The project

Applications are invited for a 3-year funded PhD studentship at the University of Birmingham, UK.  Under the supervision of Dr Richard Shelton, Dr Owen Addison, Prof Paul Cooper and Prof Gabriel Landini, the PhD student will explore ‘Developing a 3D organotypical model to assess skin and gum penetrating implant soft tissue outcomes and implant device development’

Dental implants are routinely used as one facet of dental treatment and represent a multibillion global market. Their success requires predictable integration of the implant into bone and stability of the surrounding soft tissues over their lifetime. Soft tissue breakdown and inflammation related to dental implants is widespread (80%) and can progress to the underlying bone (28-56%), which leads to pain, a requirement for revision surgery or implant loss, which is undesirable for both patient and health service provider.

The outcome of soft tissue implant interactions are complex and there is an extensive volume of research and development intended to improve implant integration, maintenance and clinical outcomes. Unfortunately much of the pre-clinical evaluation uses animal-test methods which the current proposal aims to eliminate.

As part of this PhD project, the student will develop an animal free model from one we have already established for generating three dimensional cultures of oral keratinocytes, but the current project will utilise solely human cells isolated from fresh waste human tissue following surgical extractions and oral surgery which release normal oral mucosa. The keratinocytes and fibroblasts will be established and cultured three dimensionally on human de-epidermalised dermis to allow stratification using serum free culture medium before transferring to inserts within 6 well plates for placement of implants into model surgical sites created using a tissue biopsy punch. Keratinocyte responses to different tooth root implant materials and surface treatments will be assessed using routine histology and immunohistochemistry for localisation of specific markers associated with oral keratinocytes in association with quantitative image analysis and gene expression (to include E-cadherin, plakophilin, desmocollin-3, desmogleins-3 and cytokeratins-1, -5, -6, -10, -13) analysed using RT-PCR. This will examine how the implant materials and treatments influence the development and morphology of the epithelial attachment and the profile of gene expression of the peri-implant keratinocytes to identify features that will enhance incorporation and survival of the implants.

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The ultimate aim of the PhD is to be able to more closely mimic the in vivo environment and model clinical outcomes for tooth root implants in vitro to identify strategies for improving clinical performance whilst also removing the requirement for the use of animals. The PhD student will also investigate and develop a loading regime for the implants in culture which at present is lacking from any other in vitro models. This will enable comparison with static or unloaded implants and identify the influence loading implants has on the biological responses of keratinocytes and thereby maximise the clinical relevance of data obtained.

Candidate requirements

To be eligible, applicants should hold a first/upper class second Honours degree in a relevant biological/biomedical science. In addition, experience in cell culture is desirable.

The PhD studentship is available immediately and would be expected to be taken up no later than January 2014.

Funding

Due to funding restrictions the position is funded for 3 years (fixed annual stipend; fees at Home/EU rate; consumables) through a grant from the Dr Hadwen Trust for Human Research.

How to apply

To apply, please send:

  • a covering letter highlighting your research experience/capabilities;
  • a detailed and up-to-date CV, including the contact details of two referees;
  • copies of your degree transcripts;
  • evidence of your proficiency in the English language, if applicable (IELTS, TOEFL).

To: Dr Richard Shelton ([email protected]) by the 31st October 2013.

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