Table 2 Comparing the advantages and disadvantages of hydrogel crosslinking methods
From: Developing hydrogels for gene therapy and tissue engineering
Type | Crosslinking method | Principle | Advantage | Disadvantages |
|---|---|---|---|---|
Physical crosslinking | Ionic crosslinking | Ionic bond | Improved thermal stability and mechanical strength | Limited biocompatibility, and sensitive to environmental factors |
Base pairing | Hydrogen bond, double-stranded interaction | Strong recognition ability, accuracy, sensitivity | Poor mechanical properties, and complex preparation process, and high cost | |
Thermotropic phase transition | Temperature change | Low toxicity, in situ curing | Low mechanical properties, temperature sensitive | |
Molecular-specific recognition | Van der Waals forces and electrostatic interactions | High specificity and sensitivity, good stability, and good biocompatibility | Precise control of the preparation process, and sensitive to environmental factors | |
Chemical crosslinking | Schiff base reaction | Nucleophilic addition elimination, lone electron pairs | Self-healing hydrogel, multi-responsiveness, low energy loss, and simple process | Mechanical properties, poor biological activity |
Diels–Alder reaction | Addition reaction | Thermo-responsive, mild reaction conditions, and no byproducts, high yields, and good stability | Low mechanical properties, biosafety needs further research | |
Michael addition | Nucleophilic addition | Mild reaction conditions, high selectivity, high yield | Low mechanical properties, sensitive to environmental factors | |
Click chemical reaction | Azide compounds, triazole compounds | Mild conditions, fast reaction rate, good selectivity, and easy purification | Low mechanical properties, sensitive to environmental factors, may trigger an immune response, or are potentially toxic | |
Free-radical polymerization | Free-radical polymerization, covalent bond | High selectivity, fast reaction rate, strong controllability, simple production process, easy to serialize | Heat build-up is difficult to control, the initiator may be toxic, and there is a wide molecular weight distribution | |
Enzyme crosslinking | RNA or protein | Specificity, selectivity, mild reaction conditions, good biocompatibility of products | Strongly affected by environmental factors, lower mechanical properties of the product | |
Chemical crosslinker | Role of crosslinking agents | Enhanced stability and durability, improved material temperature and chemical stability, gentle, easy to handle, easy to control | Causes material shrinkage or side reactions, loss of product quality, and material calcification |