Towards the development of a physiologically mimetic tissue engineered cardiovascular graft for the treatment of abdominal aortic aneurysms

With cardiovascular pathologies continuing to prevail, effective arterial replacements for the minimally invasive treatment of abdominal aortic aneurysms (AAAs) through endovascular aneurysm repair (EVAR) are still an under-developed approach. A proposed solution to the identified problems of EVAR, including stent-graft migration and endoleaks, focuses on the use of a tissue engineered (TE) collar to create a biological seal between the device and the host artery. TE acellular vascular grafts are an emerging concept with the development and optimisation of biological scaffolds composed of naturally derived ECM, such as small intestinal submucosa (SIS) and urinary bladder matrix (UBM), receiving significant attention in the field of TE. In this research material characteristics such as scaffold surface topography and material wettability, of both naturally derived ECMs and comparative synthetically engineered materials were evaluated. As efficient endothelialisation is a desirable characteristic, cellular adhesion and proliferation as well as the interaction between the scaffold material and vascular cells were examined together with an assessment of scaffold mechanical behaviour. Overall, naturally derived ECM scaffolds demonstrated superior biocompatible surfaces for cellular growth, adhesion and proliferation while also exhibiting the biomechanical properties necessary to withstand the in vivo environment and providing improved compliance than currently employed synthetic materials. A factor currently limiting the success of biological scaffolds is effective shelf stable storage. This research demonstrated the viability, mechanical integrity and bioactive potential of ECM stent-grafts as suitable off-the-shelf vascular prosthetic devices. The effect of long-term hydrated storage in stented and un-stented configurations on the mechanical performance and bioactive potential of SIS and UBM were analysed. Additionally, inflammatory inducing cellular remnants leached after hydrated storage of single and multi-ply ECM scaffolds were quantified and the effect of such leached products on cellular proliferation was investigated. Residual DNA present in the scaffold after the hydration period was also evaluated. Results from these studies indicated a globally beneficial effect of hydrated storage on ECM material performance at both a biomechanical and biological level with hydration also facilitating the removal of residual cellular remnants from the ECM scaffolds prior to implantation. Due to the inherent similarities of ECM composition and the intended vascular site of implantation, the potential of decellularised porcine aortic tissue to develop a novel acellular TE collar material was investigated. Material decellularisation was examined with extensive evaluation of mechanical properties and residual cellular remnants. The resulting decellularised scaffolds demonstrated successful cellular adhesion indicating the potential of the material as a vascular graft upon implantation. Overall, the findings from this research further the current knowledge relating to shelf stable storage of ECM materials and confirm the significant potential in developing a physiologically mimetic tissue engineered cardiovascular graft for the treatment of AAAs, which can be delivered as an off-the-shelf product.