Development of antioxidant-loaded dermal formulations for diabetic wound healing.

Diabetic wounds and pressure ulcers affect 26 million patients annually[1]. Limited treatment options make diabetic pressure ulcers difficult to heal leading to sepsis, amputations, and social dysfunction[2,3]. Angiogenesis is critical for wound healing, as cells proliferate and migrate to repair tissue. Oxidative damage hinders this process, delaying tissue repair and regeneration in diabetic patients [4,5].

Antioxidants, such as hydrogen sulfide donors, withaferin-A, and epigallocatechin gallate(EGCG), show promise in enhancing angiogenesis and mitigating oxidative damage and inflammation. Withaferin-A reduces oxidative stress and inflammation, supporting vascular health. EGCG protects endothelial cells, reduces oxidative stress, and improves endothelial function-crucial in diabetic wounds. Its anti-inflammatory effects further aid vascular health and wound healing. ADT-OH, a hydrogen sulphide-donor, promotes vasodilation, reduces oxidative stress, and supports re-epithelialisation and collagen deposition, essential for wound repair[6,7].

However, rapid release rates and instability limit antioxidant delivery. To address this, we aim to develop novel dermal formulations loaded with antioxidants and evaluate their potential using a 3D-diabetic wound model. This approach could offer an effective therapeutic strategy to enhance wound healing and reduce complications in diabetic patients.

Aim: Develop and characterise biocompatible dermal gel formulations loaded with antioxidants to promote angiogenesis and re-epithelialisation in a 3D-diabetic wound model.

• Objective 1: Synthesis and characterisation of gels: Antioxidant-loaded gels will be developed and assessed using texture analysis and differential scanning calorimetry.
• Objective 2: Diabetic skin model: Co-culture of human umbilical vein endothelial cells and dermal fibroblasts will be established with keratinocytes seeded on top. Hyperglycaemic conditions will mimic diabetic inflammatory environment. Inflammatory markers (e.g., IL-6, ROS), cell viability, and morphology will confirm model accuracy.
• Objective 3: Formulation efficacy: Compound release will be assessed using HPLC-UV. Safety will be evaluated with Cell Titer blue assay, and wound healing potential tested by measuring wound closure rates and analysing inflammatory and oxidative stress markers.

References:

• Yazdanpanah, L., et al. (2018). International Journal of Endocrinology, 2018, 7631659.

• Sen, C. K., et al. (2009). [Journal title not provided], 17(6), 763–771.

• Wu, L., et al. (2015). Cochrane Database of Systematic Reviews, (7).

• Gallagher, K. A., et al. (2007). [Journal title not provided], 117(5), 1249–1259.

• Frank, S., et al. (1995). [Journal title not provided], 270(21), 12607–12613.

• Xu, M., et al. (2021). Journal of Advanced Research, 27, 11–17.

• Zhao, X., et al. (2020). Acta Biomaterialia, 104, 85–94.

Supervisors:

Dr Mandeep Kaur Marwah

Dr Lissette Sanchez-Aranguren

Dr Shakil Ahmad

PhD programmes are for those who are seeking to develop greater in-depth knowledge in a specific area. Completing this level of study is about making an original contribution to knowledge, making new discoveries and developing lifelong skills. 

At Aston University, our Engineering and Physical Sciences PhD programmes will provide all the support and facilities you will need to develop into a leading researcher in your chosen field.  You will be welcomed into a supportive community with a shared enthusiasm for original research, where diversity and multidisciplinary is championed.

Person Specification

Candidates should have been awarded, or expect to achieve, EITHER:

• A Bachelors degree in a relevant subject with an award of First Class or 2.1. 

OR 

• A Bachelors degree in a relevant subject with an award of First Class or 2.1, and a Masters degree in a relevant subject with an award of Merit or higher.

Qualifications from other countries which are considered by Aston University to be equivalent to that described above will be eligible to apply.

Submitting an application

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected. Your application must include: 

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor's degrees.
    
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count. 
    
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience. 
    
4. Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary. 
    
5. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage. 
    
6. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.  

Studying a PhD is great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, PhD education will help you to develop a set of valuable transferrable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.

The variety of PhD project topics at Aston means that the destinations of our graduates vary substantially. Some choose to continue into academia, at either Aston or other leading institutions, while others go onto use their newly acquired skills in a range of research, healthcare, industry or charitable fields. When selecting your chosen PhD path at Aston, your supervisor will be able to provide you with relevant career opportunities that could be available to you in your specialist area.