AbstractCardiovascular disease is the principal cause of death worldwide. Common manifestations are peripheral arterial disease (PAD) and coronary heart disease (CHD), which develop as a consequence of the critical atherosclerotic narrowing of supplying arteries. Prompt restoration of downstream blood flow is essential to avoid the onset of chronic or acute of both pathologies.
Cell therapy has been explored as solution to promote revascularization for patients with severe condition of PAD in which surgical revascularization is not suitable, but this approach showed limitations with regards of delivery and efficacy of cell homing.
On the other hand, coronary artery bypass grafts (CABG) remains the preferred therapy for the majority of patients with CHD. Autologous vessels, such as the saphenous vein and internal thoracic artery, represent the gold standard for grafting small-diameter vessels. However, they require invasive harvesting and show low long-term patency rate due to intimal hyperplasia and imposed atherosclerosis.
This thesis aims to reach two principal goals: 1) design and manufacture composite hybrid scaffolds cellularized with human vascular cells for perivascular promotion of arteriogenesis in a murine model of limb ischemia; 2) generation of three-layered small-size vascular graft (VG) resembling the complexity of an artery to address the unmet clinical need and shortage of natural arterial grafts. Aiming at overcoming the limitation of traditional clinical approaches, multi-scale composite scaffolds developed in this work have proven the capability to deliver efficiently pro-angiogenic cells in the target ischaemic area and to improve the process of collateral formation. This thesis also provides the evidence of the success of the hybrid-VG fabrication approach which led to the development of a prototype of biocompatible living vascular conduit using innovative cellularization techniques. In fact, the capability to generate a graft which possesses distinct and well organized cellular layers, matching the structure of the native artery, provides the potentiality to integration and remodelling in a physiologic manner following implantation in vivo.
The evidences shown in this thesis, centred on Tissue Engineering approaches, may represent exciting alternatives of current clinical approaches.
|Date of Award||19 Mar 2019|
|Supervisor||Paolo R Madeddu (Supervisor) & Bruce W Drinkwater (Supervisor)|
- Tissue Engineering
- Regenerative medicine
- Stem cells