Cardiovascular Research Unit
Although 2013 continued to remain financially challenging, the Western Cape Heart Research Grouping of the Medical Research Council, of which the Cardiovascular Research Unit is a member, continued to support essential basic research and will continue to do so in 2014. The Unit also relies on National Research Foundation research grants.
A significant breakthrough in our synthetic vascular graft research was achieved in the previous year where spontaneous endothelialization of the luminal surface across an engineered porous graft wall was shown to be independent of trans-anastomotic outgrowth. A confluent endothelial lining in small diameter vascular grafts remains the ‘Holy Grail’ in humans and is essential for long-term patency.
In 2013, the breakthrough results on porous polyurethane grafts were published in an international peer reviewed journal and followed by a successful study to elucidate and differentiate between the two non-trans-anastomotic modes of healing, namely transmural and fallout healing. The former was shown to be the most prevalent and reliable. These findings may be useful for the development of clinical peripheral vascular (including endolumenal) grafts, as transmural endothelialization remains a viable healing mode in humans. Continued work in this field in 2014 will focus on accelerating the healing response.
A collaboration with Gothenburg University in the field of vascular grafts was concluded, with publication of the results anticipated in 2014. Similarly, publication of the initial results on our studies with Clemson University on the use of elastin-derived grafts is imminent, and work continues in a large animal model.
Research continued to focus on a regenerative medicine approach based on remodelling of synthetic engineered hydrogels. A model for assessment of the regenerative capacity of these synthetic hydrogels in the treatment of myocardial infarction has generated further promising results. Therapeutic benefits with respect to cardiac function and scarring were shown for hydrogels carrying growth factor coacervates. Strong preliminary data has been obtained showing both improved engraftment and therapeutic effect of stem cells delivered with the synthetic hydrogel into infarcted hearts. Synthetic ‘smart’ hydrogels were also developed that were shown to control invasion of specific cell types, a finding that has generated considerable international interest in the field of tissue regeneration.
Building on the groundwork laid down in 2012 with respect to porcine pericardial tissue, research evaluating the immune and inflammatory cell responses as well as the potential for mineralisation and resorbtion of animal tissue used in the construction of ‘bioprosthetic’ transcatheter heart valve designs, in 2013 concentrated on understanding the benefits of tissue decellularisation, the introduction of different covalent ‘cross-links’ and capping alternatives and the use of non-covalent agents when applied to bovine pericardium. A short list of regimens emerging from that research are already undergoing preclinical testing in a circulatory model.
Milestones of the Biomechanical Sciences Group in 2013 included the successful completion of a 3-year project into biomechanics of biomaterial therapies for myocardial infarction funded from the South African Centre for High Performance Computing; the commencement of an interdisciplinary collaborative project aiming at reducing the failure rate of arterio-venous access for haemodialysis in patients with end-stage renal diseases and the graduation of two M.Sc.(Med) students with distinction. The group also extended its activities in the biomechanics of single cells through organization of an international event on cell mechanics and mechanobiology in Cape Town with speakers from the UK, Germany, Spain and South Africa that included a meeting with the UK Minister for Science and Universities, Rt. Hon. David Willets.