From:  Injectable biodegradable hydrogels for in situ tissue engineering

 Comparison of crosslinking mechanisms for injectable hydrogels.

Mechanism typeChemistryGelation timeMechanical properties (G')Self-crosslinking capability
Physical-IonicAlginate + Ca2+, chitosan + tripolyphosphateSeconds–minutesLow–moderate (~10–1,000 Pa)Limited (requires ion source)
Physical-ThermalPluronic F127, PNIPAMMinutesModerate (~1–10 kPa)Yes (temperature-dependent)
Physical-SupramolecularCyclodextrin-polymer, peptide assembliesSeconds–minutesLow–moderateYes (host-guest, H-bonding)
Chemical-EnzymaticTransglutaminase, HRP/H2O2MinutesModerate–high (~1–20 kPa)No (requires enzyme)
Chemical-Photo-crosslinking*GelMA/PEGDA + UV/VisSeconds–minutesTunable (~0.1–100 kPa)No (requires photoinitiator + light)
Chemical-Click chemistryThiol-ene, Diels-Alder, azide-alkyneMinutes–hoursHigh (~5–50 kPa)Limited (requires catalyst)

* Photo-crosslinked GelMA-based hydrogels are already in a preclinical phase of testing as a cartilage repair and ocular surface reconstruction material.