Table 1.

Advantages and disadvantages of crosslinking methods.

Crosslinking methods	Advantages	Disadvantages
Self-assembly	No crosslinkers required; reversible; mild gelation upon exposure to external stimuli (e.g., pH, temperature, etc.)	Typically mechanically weak gels
Photocrosslinking	Spatiotemporal control over gelation	Light source and initiator required
Thiol/acrylate Michael reaction	High specificity; controllable gelation kinetics; mild gelation under physiological conditions	Sometimes an organic base (i.e., triethanolamine) used
Disulfide formation	High specificity; controllable gelation kinetics under physiological conditions	Oxidizing agents often required
Schiff’s base reaction	Controllable gelation kinetics; mild gelation under physiological conditions	Lack of specificity: aldehyde groups can react with amines of bioactive factors and tissue extracellular matrix molecules
Enzyme-mediated reaction	High specificity; gelation in mild conditions	Instability of some enzymes; active enzymes may remain following gelation
Click reaction	High specificity; high reaction efficiency; controllable gelation rate	Toxic Cu(I) catalyst often required
Ionic crosslinking	Gelation in mild conditions; potentially reversible	Charged therapeutics may interfere with crosslinking
Molecular recognition	High specificity; gelation in mild conditions	Sometimes mechanically weak gels and rapid degradation