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. 2022 Dec 23;1(1):e20220011. doi: 10.1002/SMMD.20220011

TABLE 1.

A summary of cross‐linking methods of silk fibroin hydrogels

Classification Methods Advantages Disadvantages Ref
Physical cross‐linking Temperature
  • Mild and easy condition

  • No toxic agents

Slow gelation 48 , 49 , 51 , 52
Shear forces
  • Simple operation

  • No toxic agents

  • Directional gel structures

Relatively high gelation concentration 53 , 54 , 55
Ultrasound
  • Rapidity and controllability

  • Environmental protection

  • No toxic agents

High ultrasonic intensity 56 , 57 , 58 , 59
Polar reagents Rapid and easy processing Cytotoxicity 60 , 61 , 62 , 63
pH Promoted gelation process
  • Acid condition

  • Cytotoxicity

48
Carbon dioxide
  • Directional gel structures

  • No toxic agents

Slow gelation 65 , 66
Electric field Free of residual acids or chemical cross‐linkers
  • Long processing time

  • Stiff gel

67 , 68
Surfactants Accelerated gelation Release of surfactants 70 , 71
Chemical cross‐linking Enzymatic cross‐linking
  • Moderate reaction

  • Biocompatibility

  • Elastic gel structures

Time‐consuming 72 , 73 , 74 , 75
Chemical agents Rapid gelation Cytotoxicity (some agents) 76 , 77 , 78 , 79 , 80 , 81 , 82
Photo cross‐linking Efficient, rapid and, mild process Cytotoxicity 83 , 84 , 85 , 86
Irradiation Satisfactory rapidity High energy consumption 91 , 92