Vascular endothelium-supporting materials: Understanding the structural and physicochemical requirements.

• Applicant: Professorin Dr. Iwona Cicha, Ph.D.
• Subject Area: Biomaterials ; Coating and Surface Technology ; Cardiac and Vascular Surgery ; Polymeric and Biogenic Materials and Derived Composites ; Polymer Materials ; Cell Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465174243

Small-diameter vessel replacement by autologous vessel transplantation is limited by the low availability of suitable graft tissue in many patients. Previous attempts at tissue-engineered vascular grafts for small diameter vessels had little clinical impact, failing in mechanical stability or in biological performance. These failures have been closely related to the fact that there is an insufficient basic knowledge regarding the response of human endothelial cells (ECs) to the properties of graft materials. In the focus of this project are the detailed and systematic investigations of the material properties and the biological requirements for development of improved vascular prostheses based on polyurethane, which support rapid endothelialization and possess adequate mechanical properties to replace damaged vessel in vivo. The main hypothesis of our project is that effective colonization of polymeric scaffolds with ECs depends on the specific structural properties of the material and can be controlled by their modifications. Secondary hypothesis is that by using cell-attracting coating, it is possible to enhance the endothelialization-supporting properties of scaffolds.To test these hypotheses, the following main aims will be pursued:(1) Systematic investigation of the effect of polymer scaffold properties (structure (fibrous vs porous), fiber size, pore size, porosity, scaffold thickness, among others) on the scaffold endothelialization and the extensive physicochemical analyses in 2D and 3D.(2) Surface modifications with bioactive coatings (including polydopamine, polytyrosine, polyphenylalanine and polyethylphenylamine, as well as dual coatings involving peptides REDV, YIGSR, IKVAV, CAG), and the detailed investigation of their effect on the colonization of scaffold with vascular cells.(3) Functional evaluation of the tubular grafts, including (a) analyses of hemocompatibility and thrombogenicity under static and dynamic conditions; (b) evaluation of three pre-endothelialization approaches: magnetic endothelial cell (EC) seeding on the luminal surfaces of the grafts, static cell seeding and perfusion seeding; and (c) analysis of endothelial response to inflammatory stimuli under flow conditions.(4) Validation of in vitro results in the in vivo sheep model to test for improved endothelialization and patency of modified tubular scaffolds as compared with control scaffolds of pristine polyurethane.The analysis of surface-cell interactions, and of the effect of coating on the endothelialization process will result in generating a large, detailed database of new knowledge in the field of material engineering. Thanks to determining the requirements and procedures needed to effectively colonize the material with vascular cells this project will also contribute to an improved technology for the future production of blood vessel substitutes, allowing prediction and translation also to other biocompatible polymeric materials.

• DFG Programme: Research Grants
• International Connection: Poland
• Cooperation Partner: Professor Dr.-Ing. Tomasz Ciach