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. Author manuscript; available in PMC: 2022 Jul 1.
Published in final edited form as: Trends Biotechnol. 2020 Dec 2;39(7):719–730. doi: 10.1016/j.tibtech.2020.11.003

Table 2.

Silk fibroin gelation processes

Crosslinking process Examples Advantages Disadvantages Ref.
Physical

  • Temperature

  • pH change

  • Solvent removal

  • Sonication

  • Glycerol/PEG

  • Salts

  • Electric stimuli

 No chemicals
Inexpensive		 Physical bonding
Slow kinetics
Poor controllable
Stiff gels (β-sheets)
Opaque gels		 [5,67,68]
Covalent Enzymatic:

  • Horseradish peroxidase

  • Transglutaminase

 Mild conditions
(temperature, pH)
Covalent bonds
Transparent gels
Elastic gels		 Cost
Selective
Variable kinetics
Stiffening with time		 [5,72]
Photo-polymerization:

  • Riboflavin

  • Acrylate/Methacrylate addition

  • Ruthenium

 Controllable
Rapid gelation
Tunable crosslink density
Covalent bonds
Clear gels		 Post-processing extraction
UV light
Toxicity of photo-initiators		 [39,67,75,78]
Chemicals:

  • Glutaraldehyde

  • Genipin

  • Carbodiimide reaction

 Genipin - natural crosslinker
Covalent bonds		 Toxicity of glutaraldehyde
Slow gelation
kinetics with genipin		 [5,67,79]