Dermal delivery of hydrogen sulphide donors in the treatment of diabetic pressure ulcers

Diabetic wounds associated with pressure ulcers are a worldwide concern affecting around 26 million patients annually with 15-25% of diabetic patients developing foot ulcer during their lifetime [1]. With limited treatment options, diabetic pressure ulcers are difficult to heal and prone to infection leading to further complications such as sepsis, amputations and significant social dysfunction [2, 3]. Angiogenesis is essential during wound healing during which cells proliferate and migrate into the wound. However, these events are impaired in wound healing processes involving diabetic patients [4, 5]. Hydrogen sulphide (H₂S) is an essential gaseous signalling molecule crucial in wound healing by promoting angiogenesis, re-epithelialisation and collagen deposition [6, 7]. Nonetheless, there are many delivery challenges associated with H₂S donors, including their rapid H₂S release rates and donor instability. We aim to address these limitations by generating novel dermal H₂S-donor loaded formulations and test their translational potential on an in vitro diabetic wound model.

Objectives

This translational and interdisciplinary project aims to develop and characterise novel biocompatible dermal gel formulations loaded with various H₂S-donors whilst testing their ability to promote angiogenesis and re-epithelialisation in a 3D cell culture diabetic wound model.

Proposed methods

Synthesis of dermal gel formulations: Gels loaded with H₂S-donors will be developed and characterised using techniques such as texture analysis and differential scanning calorimetry. Diabetic skin model establishment: A co-culture with human umbilical vein endothelial cells and human dermal fibroblasts will be established using a layer-by-layer method (with fibronectin and gelatine). Keratinocytes will be seeded on top of this co-culture. These will be cultured in growth medium containing levels of glucose mimicking hyperglycaemia. Formulation characteristics: H₂S release will be characterised with HPLC-fluorescent detection and safety will be established by assessing cell viability using the Cell Titer blue assay. Wound healing assessment: The potential of H₂S-donor formulations to improve wound healing in the cellular skin model will be determined by assessing wound closure rates.

Estimated yearly cost of consumables

£3000 per year

Person Specification

A Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution)

Submitting an application

As part of the application, you will need to supply:

·        A copy of your current CV

·        Copies of your academic qualifications for your Bachelor degree, and Masters degree (if studied); this should include both certificates and transcripts, and must be translated in to English

·        A research proposal statement*

·        Two academic references

·        Proof of your English Language proficiency

Details of how to submit your application can be found here. 

*The application must be accompanied by a “research proposal” statement. An original proposal is not required as the initial scope of the project has been defined, candidates should take this opportunity to detail how their knowledge and experience will benefit the project and should also be accompanied by a brief review of relevant research literature.

Please include the supervisor’s name and project title in your Personal Statement.

If you require further information about the application process please contact the Postgraduate Admissions team at [Email Address Removed]