Textile-templated anisotropic electrospun scaffolds for cardiac tissue engineering

Myocardial infarction (MI) and end-stage heart failure represent some of the major life-threatening pathologies. Current conventional treatments of the aftermath of MI involve promoting revascularization to protect residual cells and slowing down the progression of heart failure. However, these treatment modalities fail to restore the ability of the heart to provide adequate blood supply. In spite of promising preclinical results, most clinical trials have shown that the long-term outcome of cellbased therapies does not exceed that of conventional pharmacological intervention. For end-stage patients, heart transplantation is the only alternative, which remains limited due to the shortage of donor organs and to the potential for rejection of the donated organ. Therefore, current studies focus on bioengineering approaches for creating cardiac patches that will assist in restoring cardiac function, by repair and regeneration of the myocardium. This thesis presents a novel approach for creating bioactive anisotropic cardiac patches. Our approach is based on a combination of biomedical and textilemanufacturing techniques in concert with nano-biotechnology based tissueengineering stratagems. Using jersey-knitted textiles, made of cotton or polyester yarns as template targets, I successfully produced anisotropic three-dimensional electrospun scaffolds with diverse architectures and patterns. By comparing scaffolds made of poly(lactic-co-glycolicacid) and polycarbonate urethane (Bionate®), I concluded that elastomeric Bionate® is a suitable candidate material for constructing functional anisotropic contractile cardiac patches. The ultra-structure and mechanical properties of textile-templated scaffolds significantly differ from those of scaffolds electrospun from the same materials onto conventional 2-D flattarget electrospun scaffolds. Textile-templated scaffolds supported the adhesion and proliferation of H9C2 cardiac myoblasts and murine neonatal cardiomyocytes and guided the cardiac-like anisotropic organization of these cells in vitro. The functionality of anisotropic 3-D electrospun scaffolds was further tested by seeding with murine neonatal cardiomyocytes and assessing their spontaneous contractile properties in vitro. My results indicated that knitted polyester-templated fibrous scaffolds that were manufactured using our new technique were significantly more effective compared to two control groups. The methods described in this thesis take advantage of established textile manufacturing strategies as an efficient and costeffective approach to enhance the complexity of 3-D scaffold structures for cardiac tissue engineering and regenerative medicine.