Speaker
Description
"Introduction
In present times, implant development focusses on optimizing biocompatibility, mechanical strength, and reproducibility. Although cardiovascular implants currently available on the market are medically established and therefore widely used, they have a limited lifetime which also impacts the mechanical properties and functionality. Additional issues are the formation of blood clots in mechanical implants (heart valves), the formation of bacterial biofilms (dental implants), and the degradation of bioprotheses. Also, implant rejection by the patient’s body is still a challenge. A solution for these issues can be the use of biohybrid hydrogels. Especially fibrin-based hydrogels are very promising.
Methodology
The aim of this research is the synthesis and characterization of fibrin-based hydrogel-matrices for Tissue Engineering applications with the research focus on cardiovascular implants, to be precise on heart valve replacements. We have reinforced fibrin by the addition of linear functional copolymers, specific fibrin-binding peptides, and functional microgels. Our goal is to establish an innovative functional tool-box for fibrin-based biohybrid hydrogels that allow also for patient-specific individualisation of implants. The effect of incorporated functional additives in the hydrogel-matrices is analyzed in regard to their mechanical properties, fiber-network morphology and biocompatibility.
Results
In terms of our research, we could already demonstrate that the addition of linear poly(N-vinylpyrrolidone)-copolymers with functional epoxide groups can enhance the mechanical behavior of the fibrin-based hydrogels due to covalent crosslinking, resulting in higher storage moduli, thicker fibers, and a decreased degradation rate compared to pure fibrin-hydrogels. The obtained hydrogels additionally possess a high biocompatibility as proven by cell viability experiments.
In addition, specific fibrin-binding peptides were applied, which exhibit supramolecular interactions within the fibrin-matrix. A combination of supramolecular and covalent interactions by mixing linear polymers and fibrin-binding peptides in various ratios can enhance the strain-stiffening behavior of the hydrogel matrix. Also, the fiber thickness could be increased.
As a third modification of fibrin-based hydrogels, functional thermoresponsive microgels were used instead of linear copolymers and specific peptides. Just like the linear copolymers, the N-vinylcaprolactam-based microgels include glycidyl methacrylate as a functional comonomer to enable covalent attachment to the fibrin by epoxide groups. We can demonstrate that the use of microgels as colloidal crosslinkers resultes in hydrogels providing a temperature-dependent increase in storage modulus, which is not present in pure fibrin-gels. As microgels are widely studied for their possible application in drug delivery, owing to their ability to encapsulate active substances, their use is of high interest in Tissue Engineering applications.
Conclusion
We could develop a functional tool-box for the reinforcement of fibrin-based hydrogels. The mechanical and morphological properties can be tailor-made by selecting the respective type of additive. Regarding the Tissue Engineering of materials mimicking native heart valves, compartments with different mechanical properties are needed, which is exactly what our tool-box allows us to create."
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