Application deadline: 3rd March
Interviews to be held: 31 March 2021
The first semester of this project will be based at the University of Manchester and the remaining duration will be based at the University Sheffield as this CDT is a partnership between the two universities.
Coronary artery disease (CAD) is caused by narrowing of arteries due to the hardening of cholesterol, fats, and other components of the blood, causing inadequate supply of oxygen rich blood to the heart, leading to myocardial infarction. The most promising treatment of CAD is angioplasty which involves mechanical widening of narrowed blood vessels followed by the deployment of a coronary artery stent. The stent is deployed in its collapsed state and inflated inside the narrowed blood vessel, thus restoring normal blood flow.
There are three types of coronary artery stents, bare metal stents (BMS), drug eluting stents (DES) and the Bioresorbable Vascular Scaffolds (BVS). BMS and DES are metallic stents that result in foreign body reactions including inflammation, in-stent restenosis, thrombosis and stent jailing. BVS are made using bioresorbable polymeric materials which are tailored to resorb once the artery is fully repaired and its function is restored, hence preventing all the above-mentioned problems caused by the BMS and DES. However, the first BVS, ABSORB, produced by Abbott had to be withdrawn due to relatively poor clinical outcomes. The ABSORB stents had limited expansion, suffered from fracture problems, low radial strength, sub optimal strut width and negative recoiling.
The aim of this project will be the development of novel Polyhydroxyalkanoate (PHA)-based 3D printed biodegradable coronary artery stents with tailorable mechanical properties, degradation rates, produced using patient specific CT scans and hence bespoke to specific patient needs, an absolutely unmet clinical need.
Main questions to be answered:
1. Optimal conditions for the production of a range of different PHAs including scl-PHAs, mcl-PHAs and scl-mcl-PHAs (copolymers).
2. The optimal PHA blend/PHA copolymer with the required mechanical properties for a coronary artery stent (high Young’s modulus and reasonable elongation at break, enabling the stent to inflate and provide the required stiffness and radial strength).
3. The optimal PHA blend/ copolymer with the required degradation rate. Ideally the stent needs to degrade completely within 2 years.
4. The in vitro biocompatibility and haemocompatibility of the developed material
5. The optimal conditions for 3D printing of the stent using the chosen PHA blend/copolymer.
6. In vitro functionality of the 3D printed stents to be tested using a Biomechanical Reactor System (BMRS) provided by BioCompatible Engineering Solutions where the conditions within a coronary artery will be simulated.
This project involves the use of a unique family of biomaterials, Polyhydroxyalkanoates (PHAs). These are a highly biocompatible and biodegradable family of natural polymers, produced by bacterial fermentation and have huge potential as advanced biomedical materials. PHAs exhibit a range of mechanical properties, hence PHA blends or PHA copolymers can be used to achieve the optimal demanding mechanical properties required for a stent. Also, the rate of degradation of the PHAs can be tailored to match the required degradation time of two years. The degradation products of PHAs are natural metabolites, such as 3-hydroxybutyryl-CoA, hence are non-toxic. Finally, and not the least, PHAs degrade via surface degradation, and hence degrade in a controlled manner, a highly desirable property for a stent.
PLACEMENT INFORMATION
(Short placements available in BioCompatible Engineering Solutions, Germany, to carry out In vitro bioevaluation of the functionality of the 3D printed stents under in vivo simulating conditions)
EPSRC Centre for Doctoral Training in Advanced Biomedical Materials
This project is part of the EPSRC Centre for Doctoral Training in Advanced Biomedical Materials. All available projects are listed here.
Find out how to apply, with full details on eligibility and funding here.
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