Table 2.

Comparative table of crosslinking methods to fabricate hydrogels for bone regeneration

Crosslinking	Advantages	Drawbacks
Photo-radical	- Fast and mild reaction by not altering pH or temperature enormously - Forming a stable crosslinked network	- May damage cells or bioactive molecules depending on the light sources - Irreversible reaction
Schiff base	- Reversible reaction with self-healing properties - Mild reaction condition	- Relatively low stability of pseudocovalent bond - Need to prepare two separate reactive polymers
Michael addition	- Forming a stable crosslinked network - Self-healing properties under certain conditions such as excess presence of thiols	- Potential side reaction to form unexpected disulfide bonds - Need to prepare two separate reactive polymers
Diels-Alder	- Specific bio-orthogonal reaction - No side reactions and byproducts	- Need to prepare two separate reactive polymers - Considered as an irreversible reaction under physiological condition (reversible at extremely high temperature above 800K)
Enzyme	- Fast and mild reaction with controlled gelation kinetics - Forming a stable crosslinked network	- Short half-life of enzymes - Enzyme potentially involving in inflammatory reaction by activating cytokines - Irreversible reaction
Ionic	- Fast and mild reaction - Reversible reaction with self-healing properties	- Relatively low stability - Possibly disrupt the crosslinking by ion bleaching
Hydrogen bond	- Fast and mild reaction - Reversible reaction with self-healing properties	- Relatively low stability - Require multiple multivalent hydrogen bond to form hydrogel
Hydrophobic	- Reversible reaction with self-healing properties - Can form a fixed geometry using a host-guest interaction	- Relatively low stability - Potentially form a brittle network by pushing water from hydrogel network