Innovative Biological Scaffolds for Regenerative Replacement of Dysfunctional Heart Valves

Summary

The School of Biomedical Sciences invites applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2024/25.

This opportunity is open to candidates who have the means to self-fund their studies or who have a sponsor who will cover these costs. We especially welcome applications that connect to the School's core research themes and areas, which include Healthy Living and cardiovascular diseases causing health problems in ageing populations.

This core research area aligns closely with the Tissue Engineering and Medical Device interests of this project’s supervisory team. The team are well established in the investigation of medical technology solutions for repair, replacement or regeneration of tissues damaged by cardiovascular diseases, and age-related morbidity. A particular area of interest is biological scaffolds and devices for heart valve replacement.

This project will investigate the use of Supercritical Fluids to decellularise and sterilise tissue heart valves. Potential research directions include biomechanical, biophysical and biological characterisation of the tissue extracellular matrix derived scaffold; elucidating cell responses at the scaffold:tissue interface; determination of scaffold bioactivity and role in regenerative mechanisms.

Cardiovascular diseases are the leading cause of death worldwide. Advanced prevention and treatments options are required to combat the growing prevalence. Aortic valve replacement (AVR) is the gold standard treatment for severe aortic stenosis in patients who will have a limited lifespan without intervention. More than 300,000 aortic valve replacement procedures are performed annually, and this number is expected to increase due the aging global population. Advances in Medical Technology have yet to solve the outstanding issues of longer-term durability, thromboembolic risk, and regenerative capacity of current AVR devices.

Decellularisation, the process of removing cells from donor tissues whilst retaining key structural and functional properties, has emerged as a promising approach for generating biological scaffolds for heart valve replacement. Decellularised heart valves provide close to native tissue properties, reduced immunogenicity, and have potential for tissue regeneration and growth. Although decellularised heart valves have been in clinical use in some countries for more than 10 years, they are not yet routinely available in all regions of the European Continent and Global South. Refining decellularisation techniques and introducing terminal (in final packaging) sterilisation would enhance tissue processing efficiency, de-risk production, and increase technology accessibility. This will facilitate translation to commercial production, enhance patient safety, and promote further clinical adoption of decellularised heart valves.

Supercritical Fluid Technology has emerged as an important Green Technology for fabrication, extraction, and sterilisation in several medical and industrial fields. Current decellularised heart valve inventions do not include a terminal sterilisation process, instead production relies upon donor tissue screening, antibiotic or chemical disinfection, and aseptic processing procedures. This project will investigate the use of supercritical carbon dioxide to decellularise and sterilise tissue heart valves. Several potential research directions exist - these include: biomechanical, biophysical and biological characterisation of the tissue extracellular matrix derived scaffold; elucidating cell responses at the scaffold:tissue interface (using ex-vivo models); determination of underlying mechanisms crucial for successful tissue regeneration (through in vitro cell culture).

The interdisciplinary nature of the project areas provides excellent training opportunities in a broad range of techniques crossing the disciplines of biological science, engineering, and physical sciences. Potential techniques include, imaging (advanced light, atomic force, and electron microscopy), mechanical testing (tensile), ex-vivo organ culture, cell based and biochemical assays (bioactivity, viability, proteomics), histology and immunohistochemistry.

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.