PhD Study : Oxygen-generating biomaterials for use in wound dressing strategies

Apply and key information  

Summary

Background:

Tumour hypoxia is currently recognised as a negative prognostic marker in oncology and this is, at least in part, because molecular oxygen is integrally involved in the mechanism(s) by which some anticancer therapies work. Such therapies include photodynamic therapy (PDT), sonodynamic therapy (SDT) and indeed radiotherapy, where the presence of O2 ‘fuels’ stimulus-mediated generation of cytotoxic reactive oxygen species (ROS). We have recently demonstrated that calcium peroxide nanoparticles can be used to enhance PDT [1] and SDT [2]. Calcium peroxide results in the production of molecular oxygen on contact with aqueous media.  In order to design a particle that would be compatible with systemic administration, we designed our particles to be coated with a pH sensitive polymer that is stable at normal pH (pH 7.2) and dissolves at a relatively low pH (i.e. the pH of hypoxic tumours – pH 6.4 – 6.8).   This formulation, known as StimOx, is currently under investigation as an adjuvant to anti-cancer therapies such as PDT/SDT/radiotherapy and funded by an InvestNI PoC award.

StimOx could also find use in areas such as wound healing where a lack of oxygen can impact negatively on the healing process, particularly with chronic wounds [3]. Indeed, a number of commercial products are currently on the market to address this need and these include products such as Natrox, Oxyzyme and Iodozyme. We believe StimOx could provide benefit in this area because: (i) it can be integrated with therapeutics (control of sepsis) (ii) it can be formulated to respond to changing wound pH to enable oxygen production.

Project Aim:

The current project seeks to explore the potential of embedding our nanoparticle platform in various forms of biodegradable matrices with a view toward developing oxygen-producing bandage materials. The project comprises a cross-faculty multidisciplinary approach exploiting materials chemistry, materials engineering and biomedical sciences to address the following specific objectives:

1. Nanoparticle preparation with the appropriate pH response.  This will involve the design and synthesis of coatings compatible with a range of pH responses (i.e. dissolution in high or low pH) and potentially incorporating therapeutics (PDT/SDT antimicrobials). Coated particles will be characterised with respect to size, polydispersity, pH response with respect to oxygen production and in vitro toxicity, stimulus response and antiseptic potential. (Year 1).

2.  Incorporating nanoparticles into biodegradable polymeric matrices (Year 1/2). Within this objective, manufacturing technologies such as spinning and/or extrusion-based 3D printing will be investigated to produce polymeric matrices as substrates for particle incorporation. In this regard, different commercial as well as novel pH-responsive polymers will be identified and then processed by using a range of design as well as system configurations (i.e. coaxial systems), which will be further optimised in order to best mimic the characteristics of the host tissue(s), and ultimately develop patient-specific strategies.

3. Materials testing (Year 2/3). Here materials will be characterised with respect to physico-chemical (porosity, morphology, 3D architecture, wettability) and mechanical performance, oxygen production, toxicity, response stimulus (PDT/SDT and antiseptic potential) and potential for wound healing applications (in vitro; e.g. migration assay - in normoxic and hypoxic environments).

Key References:

1. Oxygen generating nanoparticles for improved photodynamic therapy of hypoxic tumours.  Sheng Y, Nesbitt H, Callan B, Taylor MA, Love M, McHale AP, Callan JF. J Control Release. 2017 Oct 28;264:333-340.

2. Patent Application (PCT - WO2018203083 (A2).  McHale AP, Callan J, Sheng Y. 2018).

3. Topical oxygen therapy stimulates healing in difficult, chronic wounds: a tertiary centre experience. Kaufman H, Gurevich M, Tamir E, Keren E, Alexander L, Hayes P. J Wound Care. 2018 Jul 2;27(7):426-433.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

  • Sound understanding of subject area as evidenced by a comprehensive research proposal

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Publications record appropriate to career stage
  • Experience of presentation of research findings
  • A comprehensive and articulate personal statement
  • Use of personal initiative as evidenced by record of work above that normally expected at career stage.
  • Relevant professional qualification and/or a Degree in a Health or Health related area

Funding and eligibility

The University offers the following levels of support:

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

  • Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
  • Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
  • Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
  • Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living

The Doctoral College at Ulster University

Key dates

Submission deadline
Friday 7 February 2020
12:00AM

Interview Date
9 to 20 March

Preferred student start date
Mid September 2020

Applying

Apply Online  

Contact supervisor

Professor Anthony McHale

Other supervisors