Flexible Shape-memory Scaffold for Minimally Invasive Delivery of Functional Tissues

Montgomery, Miles 1, 2;  Ahadian, Samad 2;  Davenport-Huyer, Locke 1, 2;  Rito, Mauro Lo 3, 4;  Civitarese, Robert 2;  Vanderlaan, Rachel 3, 4;  Wu, Jun 6;  Reis, Lewis A. 2;  Momen, Abdul 6;  Akbrai, Saeed 5;  Pahnke, Aric 1, 2;  Li, Ren-Ke 6;  Caldarone, Christopher A. 3, 4;  Radisic, Milica 1, 2, 6 

1. Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada; 2. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; 3. Division of Cardiovascular Surgery, Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, Ontario, Canada; 4. Department of Surgery, University of Toronto, Toronto, Ontario, Canada; 5. Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada; 6. Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada

Despite great progress in engineering functional tissues for repair of various organs including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold’s shape-memory was due to its physical properties, specifically the microfabricated lattice design, as confirmed by experiments and finite element modelling. Scaffolds and engineered cardiac patches (1 -cm xby 1 -cm) were folded and delivered through an orifice as small as 1 -mm i.d., recovering their initial shape upon injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of rat cardiomyocyte-based patches was equivalent to open surgical implantation in terms of vascularization, and macrophage recruitment, and cell survival. In a rat myocardial infarction model, cardiac function was significantly improved in hearts treated with a rat cardiomyocyte-based patch 6 weeks post-myocardial infarction. , but the presence of cardiomyocytes was enhanced in the injected group. Successful delivery injection of human cell derived cardiomyocyte- cardiac patches to the epicardium, aorta, and liver in a large animal, porcine model, was achieved.