Processing, mechanical properties and bio-applications of silk fibroin-based high-strength hydrogels.

Hydrogels are an attractive class of materials that possess similar structural and functional characteristics to wet biological tissues and demonstrate a diversity of applications in biomedical engineering. Silk fibroin (SF) is a unique natural polymer due to its fibrous protein nature, versatile formats, biocompatibility, tunable biodegradation and is thus a good hydrogel candidate for bio-applications. Compared to synthetic polymer hydrogels, poor mechanical performance is still a fatal drawback that hinders the application of SF hydrogels as structural materials. Researchers have attempted to develop strategies to construct silk fibroin-based high-strength hydrogels (SF-HSHs). Herein, we firstly provide an overview of the approaches of processing SF-HSHs with a focus on the physical/non-covalent crosslinking mechanisms. The examples of SF-HSHs are discussed in detail under four categories, including physical-crosslinked, dual-crosslinked, double network and composite hydrogels respectively. A brief section follows to elucidate on the gelation mechanisms of SF-HSHs before a description of the utility of SF-HSHs in biomedicine and devices is presented. Finally, the potential challenges and future development of SF-HSHs are briefly discussed. This review aims to enhance our understanding of the structure-mechanical property-function relationships of soft materials made from natural polymers and guide future research of silk fibroin-based hydrogels for biomedical applications. STATEMENT OF SIGNIFICANCE: Silk fibroin (SF) extracted from silk fibres is increasingly applied in the biomedical field, and SF hydrogel has been an emerging area for frontier bio-research. Since SF biopolymer has an intrinsic tendency to form regular β-sheet stacks, it can be processed into purely physically crosslinked hydrogels, thus avoiding the use of chemical crosslinkers. Nevertheless, akin to other natural polymers, lab-produced SF is variable (i.e. the molecular weight and distribution), and the gelation of SF hydrogel is challenging to control. In addition, hydrogels made from SF are usually weak and brittle, which hinders the wide use of this biofriendly and biodegradable hydrogel. Recently, there is a pressing need for high strength hydrogels from natural polymers for biomedical applications, and SF is proposed as a strong candidate. Therefore, we have studied the literature in the past 10 years and would like to focus on the gelation mechanism and mechanical strength of SF hydrogels for the review.