Fibrin-based hydrogels for biomedical applications

RWTH Publications (RWTH Aachen)

Abstract

Fibrin, a biopolymer involved in wound healing, is a suitable candidate for mimicking the extracellular matrix in tissue engineering. Due to some disadvantages, such as weak mechanical properties and rapid degradation, the aim of this work was to modify fibrin-based hydrogels with various additives in order to optimize them for Tissue Engineering. All additives investigated here were classified as cytocompatible by live-dead staining of mesenchymal stem cells over several days. The simplest additive chosen was a fibrin-binding peptide (FbP), which binds to fibrin due to supramolecular interaction. In the second part of this work, a copolymer of N-vinylpyrrolidone (VP) as the main monomer and glycidyl methacrylate (GMA) as the comonomer was produced using controlled radical polymerization and investigated as an additive for fibrin-based hydrogels. Unlike the peptide in the first part of the work, the copolymer binds covalently to fibrin. The influence of copolymer concentration, comonomer concentration, and molecular weight on the mechanical properties, degradation behavior, and morphology of fibrin-based hydrogels was investigated. It was found that the copolymer increases the storage modulus of the hydrogel through additional cross-linking. In addition, the additive significantly slowed down fibrinolysis. Subsequently, the adhesion properties of the copolymer-modified fibrin gels to polythioether-based samples were investigated to verify how the hydrogels would adhere to a scaffold. It was found that both the copolymer in the gel and the copolymer in the form of a coating improved adhesion. In the third part of the thesis, a combination of the fibrin-binding peptide and the copolymer as an additive was investigated. It was found that the peptide enhances strain stiffening behavior due to its supramolecular properties, while the copolymer makes the gels stronger overall. Fibrin-based gels can also be optimized to a certain extent using GMA-modified dextran. However, modified dextran proved to be less effective than the other compounds investigated here as an additive for strengthening the gels. In the last part of the study, N-vinylcaprolactam-based (VCL) microgels with GMA as a comonomer were investigated as additives for fibrin. They also increased the storage modulus, reinforced the strain-stiffening behavior, and were able to induce a certain degree of temperature sensitivity. In addition, the microgels were used as carriers for the corticosteroid dexamethasone. The release of dexamethasone from the microgels and the fibrin-based hydrogels was successfully demonstrated.

Authors 1

1. Miriam Aischa Al Enezy‐Ulbrich corresponding Aachen

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen