Functional fibrin-based hydrogels for the direction of cell/biomaterial interactions in biohybrid cardiovascular Implants.

• Applicants: Professorin Dr. Sabine Neuss-Stein; Professor Dr. Andrij Pich
• Subject Area: Biomaterials ; Medical Physics, Biomedical Technology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 402991504

The aim of the present application is to develop an innovative biobased hydrogel for the formation of functional tissues for biohybrid heart valves. For this purpose, specific signaling molecules such as the hepatocyte growth factor (HGF) are integrated with a tuned release kinetic into the gel to avoid the need for time-consuming in vitro cell culture steps. Thus, autologous stem cells can be recruited directly and wound healing and tissue integration in the area of heart valve replacement can be improved. The basis of the hydrogels is fibrin, which is produced by a cascade reaction of fibrinogen with thrombin. In vivo, it primarily serves to close wounds through plasmatic blood coagulation, accompanied by a so-called strain stiffening through the hierarchical structure of the material, in order to generate a greater barrier against blood flow. If the material is used as a basis in a tissue engineering approach, this mechanical property is advantageous, as deformations are prevented by the non-linear elastic behaviour. In the previous project phase, fibrin gels were modified with linear copolymers based on polyvinylpyrrolidone and glycidyl methacrylate and it could be shown that the mechanical properties of the fibrin were improved. Furthermore, the copolymer proved to be cytocompatible and it slowed down the degradation of the fibrin fibres. The fibrin copolymer hydrogels support the cell growth of various cell lines as well as the differentiation of mesenchymal stem cells into smooth muscle cells.In the next project phase, modified natural biopolymers such as polysaccharides will now be used instead of synthetic linear polymers, to reinforce fibrin. These are particularly suitable for this application due to their biocompatibility and their high molecular weight. In another work package, based on the structure of a natural heart valve, a compartmentalized material consisting of hierarchical layers is to be developed using 3D printing. These layers will mainly consist of fibrin-based hydrogels, collagen or elastin. In addition, fibrin-based microgels (microbeads) will be produced via microfluidics, which are supposed to contain growth factors or cells. These are implemented into the layers as needed using 3D printing. Through this system, the release of the growth factors as well as the proliferation and differentiation behaviour of the cells in the individual hierarchies can be analyzed and optimized. This structural set-up should enable targeted control of cell behaviour on and in the scaffold after transplantations.

• DFG Programme: Research Grants