Table 4.
Summary of Cross-linking Strategies to Modulate Hydrogel Viscoelasticity
| Method | Material | Effect | Compatibility with 3D cell encapsulation | Direct modulation of the viscous phase | Reference | |
|---|---|---|---|---|---|---|
| Viscoelastic substrates (time-dependent behavior, constant viscoelastic descriptors) | Polymer concentration, cross-linker ratio | PEG-alginate | ↑ [PEG spacer]: ↑ G′, ↓ G″ |
Yes | No | 57 |
| PAAm | ↑ [bis-acrylamide]: ↑ G′, ↓G″ |
No | No | 43 | ||
| HMWLP-PAAm | ↑[HMWLP]: ∼ G′, ↑ G″ |
No | No | 47 | ||
| Boronate ester-PEG | ↑ [boranate]: ∼ G′, ↑ G″ |
Not specified | No | 49 | ||
| Liquid phase viscosity | Dextran – Agarose/PAAm | ↑ [dextran]: ∼ Eeq, ↓ Einst, ↓ τrelax |
Yes | Yes | 19 | |
| Chemical cross-linking | GTA-Gelatin | ↑ [GTA]: ↑ Eeq, ↑ Einst, ↑ τrelax |
No | No | 23,56 | |
| Time-evolving viscoelastic substrates (time-evolving behavior, viscoelastic descriptors are a function of time) | Enzymatic or chemical reactions with slow kinetics | mTG-GTA-Gelatin | ↑ incubation time: ↑ Eeq, ↑ Einst, ↑ τrelax (after 1 day) |
No | No | 56 |
| mTG-Gelatin | ↑ incubation time: ↑ Eeq, ↑ Einst, ↓τretard |
Yes | No | 40 | ||
| MA-HA | ↑ incubation time: ↑ G′, ↑ G″ |
Yes | No | 59 | ||
| Photo-cross-linking (e.g., UV) | MA-HA | ↑ exposure time: ↑ G′, ↑ G″ |
Yes | No | 60 | |
| NA-HA | ↑ exposure time: ∼ G′, ↓ G″ |
Yes | No | 61 | ||
| Thioester-PEG | ↑ exposure time: ↓ relaxation curve slope |
Yes | No | 45 | ||
| Magnetic | Fe(CO)5 – PAAm/Collagen | ↑ exposure time: ↑ G′, ↑ G″ |
Not specified | No | 46,62 |
GTA, glutaraldehyde; HA, hyaluronic acid; HMWLP, high-molecular-weight linear polymers; MA, methacrylate; mTG, microbial transglutaminase; NA, nitrobenzyl acrylate; UV, ultraviolet.