Abstract
There is an increasing demand for crosslinking methods of silk fibroin (SF) scaffolds in biomedical applications that could maintain the biocompatibility, bioactivity as well as improve the water resistance and mechanical properties of SF materials. In this study, SF was crosslinked effectively with genipin which is a naturally occurring iridoid glucoside and the crosslinking mechanism was investigated through FTIR and amino acid analysis. The results showed that genipin could react with the -NH2 groups on the side chains of SF macromolecules and to form inter- and intra-molecular covalent bonds, and improved the stability of SF materials significantly. In vitro, the performances of genipin-crosslinked SF films were assessed by seeding L929 cells and compared with ethanol-processed SF films, glutaraldehyde and polyethylene glycol diglycidyl ether crosslinked ones. The genipin-crosslinked SF films showed a similar affinity to cells as ethanol-processed ones, and a higher bioactivity in promoting cell growth and proliferation, inhibition of cell apoptosis, and maintenance of normal cell cycle compared with glutaraldehyde and polyethylene glycol diglycidyl ether crosslinked SF films. These features, combined with the decrease of brittleness of SF films crosslinked with chemical methods, substantiated genipin as an effective and biocompatible agent for the manufacturing of bioactive SF materials which used as tissue engineering scaffolds and drug delivery carriers.
Highlights
The unique chemical and mechanical properties, impressive cytocompatibility and bioactivity of silk fibroin (SF) materials make silk a popular starting material for tissue engineering scaffolds used in skin, blood vessel, bone, ligament, cornea and nerve regeneration [1,2,3,4].An SF material prepared with different surface structure could induce the proliferation of corneal cells and increase the cells’ expression of extracellular matrix [5]
The genipin-crosslinked SF films showed a similar affinity to cells as ethanol-processed ones, and a higher bioactivity in promoting cell growth and proliferation, inhibition of cell apoptosis, and maintenance of normal cell cycle compared with glutaraldehyde and polyethylene glycol diglycidyl ether crosslinked SF films
These features, combined with the decrease of brittleness of SF films crosslinked with chemical methods, substantiated genipin as an effective and biocompatible agent for the manufacturing of bioactive SF materials which used as tissue engineering scaffolds and drug delivery carriers
Summary
An SF material prepared with different surface structure could induce the proliferation of corneal cells and increase the cells’ expression of extracellular matrix [5]. Physical methods include high-temperature processing, methanol/ethanol treatment and ultraviolet radiation [7]. These methods could improve the material’s water resistance but may have a negative effect on rigidity and brittleness of the scaffold in the dry state [8, 9]. There is an increasing demand for a nontoxic crosslinking method of SF in biomedical applications that could maintain the biocompatibility, bioactivity as well as improving the water resistance and mechanical properties of SF materials
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