Table 1. Common Cross-linkers for Chitosan-Based Scaffolds in the Literature.

Scaffolds	Method of Cross-linking	Cross-linkers Used	Influence of Cross-linking on Mechanical/Rheological Properties
Chitosan	Chemical cross-link – Covalent bonding	EDC/NHS64,65	Increased Young’s modulus for chitosan scaffolds with vanillin (and bioglass) compared to chitosan scaffold.79 Increased resistance to compression for glutaraldehyde cross-linked scaffolds compared to uncross-linked scaffolds, concentration dependent increase in strength for the cross-linker.81 No significant difference in Young’s modulus with different genipin concentrations (0.25 and 0.5 M final concentration) under compression.500 Increased stiffness for cross-linked scaffold with genipin compared to chitosan scaffold73
		Genipin66−78
		Vanillin500,79
		Glutaraldehyde80−83
		Schiff base reaction84
		Hexamethylene-1,6-diaminocarboxysulfonate (HDACS)74
		Citric acid85
	Physical cross-link – Other bonding	Purines – Guanosine Diphosphate4,51,86−89	Increased compressive modulus with increasing concentrations of TPP in scaffolds.93 Increased compressive strength with TPP cross-linking compared to uncross-linked scaffolds.94 Increased stiffness for cross-linked scaffold with pectin compared to chitosan scaffold73
		β-Glycerophosphate84,90−92
		Tripoly phosphate (TPP)93−98
		Copper99
		Pectin73
Chitosan-composite	Chemical cross-link – Covalent bonding	EDC/NHS100−102	Increased elastic and loss Modulus with increasing DF-P1000 cross-linker concentration (Schiff Base and EDC dual cross-linking).100 Increased modulus and compressive strength with cross-linking using glutaraldehyde (increasing concentrations and soaking time).108 Increase in compressive strength for cross-linked scaffolds with glutaraldehyde alone or in combination with calcium cations. (110) Increased compression modulus with genipin cross-linking (also with graphene oxide addition).120 Increase in compressive strength with glyoxal cross-linking compared to uncross-linked scaffolds.106 Increased compressive strength with increasing concentration of inorganic phase (GPTMS)131
		Schiff base reaction100,103−105
		Glyoxal101,106,107
		Glutaraldehyde108−116
		Genipin112,117−129
		N′-Methylene bis(acrylamide)130
		3-Glycidoxypropyl trimethoxysilane (GPTMS)131
		2-Hydroxyethyl methacrylate (HEMA)111
		Hexamethylene diisocyanate (HDI)132
	Physical cross-link – Other bonding	Tripoly phosphate (TPP)101,133−135	Decreasing compressive strength with lemon grass oil addition due to decreased H-bonding potential of HPMC.136 Increase in compressive strength with addition of calcium cations as cross-linker compared to uncross-linked scaffolds.110 Increased elastic modulus (G′) in scaffold with Mg2+ions and BMP due to increased cross-linking density.130 Increased compressive strength for DHT treated scaffolds compared to IR treated, glutaraldehyde, and HEMA cross-linked111
		Hydroxypropyl methyl cellulose (HPMC)136,137
		Calcium cations110,113,138
		Mg2+ ions130
		Dehydrothermal (DHT) Treatment111
		Irradiation treatment111
		Cu2+ ions139