Development of endothelialised small diameter tissue-engineered grafts for cardiovascular surgery

• Applicants: Professor Dr.-Ing. Aldo Boccaccini; Dr. Raminder Singh
• Subject Area: Cardiology, Angiology ; General and Visceral Surgery ; Biomaterials ; Cardiac and Vascular Surgery
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277253457

In coronary artery bypass grafting (CABG) and peripheral vascular surgery, small diameter vessels are needed to bypass the arteries narrowed by the atherosclerotic process. Being prone to thrombogenicity, currently available synthetic grafts are unsuitable for small-diameter vessel replacement. Furthermore, despite the scope and intensity of experimental work, the clinical impact of tissue-engineered small-diameter vascular constructs has been negligible so far.Within the original project, the suitability of different tissue-engineered scaffolds along with novel cell-seeding methods was investigated in order to select adequate biomaterials for cardiovascular therapy and regeneration. These proof-of-concept studies represented an important step towards fabrication of biocompatible, cell-growth-supporting vascular constructs based on natural hydrogels. In the renewal proposal, we intend to employ 3D technique to the vessel sizes that can be used for small diameter artery replacement in adult and paediatric vascular surgery. Addressing the clinical need, we aim to produce hollow cylinders composed of alginate/protein hydrogels with lumen diameters of 0.5, 1, and 2 mm. Based on the results obtained to date, we are convinced that 3D printing represents a suitable approach to the development of cell-containing biofabricated vascular scaffolds. However, printing the vascular wall, with its highly hierarchical structure, represents a challenging aim. Among the key issues that remain to be resolved in this context are the selection and composition of materials (hydrogels) and control of fabrication process to provide sufficient mechanical stability and cell survival, at relatively large lumen diameters and wall thicknesses that do not exceed the diffusion limit of oxygen. We propose to focus on the improvement of the bioprinted constructs, including optimizing bioink composition in order to enhance the cell survival and further development of the extrusion nozzle setup to fabricate tubular constructs of different lumen diameters, as well as on the improvement of lumen colonization and vascular wall hierarchical structure by layer-by-layer radial magnetic cell seeding on bioprinted scaffolds.We are convinced that by applying the cell-type supporting materials in combination with advanced bioprinting techniques, it is possible to overcome the limitations of the currently available grafts in order to fabricate vessel substitutes with improved structure and functionality.

• DFG Programme: Research Grants