Table 1.

Advantages and disadvantages of physical and chemical cross-linking.

Cross-Linking		Advantages	Disadvantages
Physical	Self-assembly	Reversible mechanism [A] [52] Compatibility with biological systems [B] [3] Shear-thinning [2] Self-healing [2]	Additional post-cross-linking [C] [42] Poor mechanical properties [D] [52] Prolonged self-healing [2]
	Ionic interactions	[A,B] [3,52] Working under mild conditions [89]	[C,D] [42,52] Exhaustive of the number of ions [42]
	Thermal cross-linking	[A,B] [3,52] Rapid reassembly to hydrogel [2] Work under physiological conditions [89]	[C] [42] Precise temperature for cell viability [2]
	Stereo-complexation	[A,B] [3,52]	[C,D] [42,52]
Chemical	Photo-induced	Stabilization of weak cross-linked hydrogels [3,6] Fast gelation [6] Spatiotemporal control of the reaction [42] Room temperature conditions [42]	Light irradiation may affect cells [3] Precise determination of photo-initiator, intensity light and exposure time [3,42]
	Click chemistry Diels-Alder SP-AAC Thiol-ene Oxime Thiol-Michael Aldehyde-hydrazide	Fast gelation (all mechanisms) [90] Mild conditions (all mechanisms) [2,90] Spontaneous reaction (all mechanisms) [90,91] Good mechanical properties (all mechanisms) [90] Not sensitive to oxygen or water (Thiol-ene) [90]	Long gelation without initiator (Diels-Alder) [92] Numerous steps for the cyclooctyne’s synthesize (SP-AAC) [90] Use of an initiator (Thiol-ene) [90] Basic pH could damage cells (Oxime) [93]
	Enzymatic	No exogenous reagents [3] Spontaneous reaction [79] Control over the reaction [79] Specificity [52] Fast gelation [89] Mild conditions [42,52]	Needs additional catalyst (enzyme): the activity can change during the storage of the stock solution [3] The costs of the enzyme are additional costs [52]