**2.2.3 Ionic interaction**

Ionic interaction is another route to construct in-situ forming hydrogels. For example, the hydrogels can be formed by ionic interactions between water-soluble charged polymers and their di- or multi-valent counter-ions. As a typical example, alginate, a naturally occurring polysacchride, can form a hydrogel network in the presence of calcium ions under physiological conditions. The mechanism underlying the ionic crosslinking is ion exchange of sodium ions by calcium ions in the carboxylic groups and subsequent formation of an egg-box structure (Gombotz & Wee, 1998). The hydrogel is degradable slowly with the diffusion of calcium ions out of the hydrogels and finally excreted from the kidney. Fur ther studies showed that alginate-based hydrogels with CaSO4 usually reveal a heterogeneous structure due to the difficulty in the control of gelation kinetics (Kuo & Ma, 2001). This phenomenon also occured for the hydrogels using CaCl2 (Skjak-Brvk et al., 1989). In contrast, CaCO3 can give homogeneous alginate hydrogel, while its low solubility is unfavourable for further biomedical application. Ma et al. reported on crosslinked alginate hydrogels using CaCO3-GDL (D-glucono-d-lactone) and CaSO4-CaCO3-GDL systems (Kuo & Ma, 2001). Gelation rates and mechanical properties of the alginate hydrogels could be controlled by varying the composition of calcium compound systems and alginate concentration, thereby giving rise to structurally uniform hydrogels.

In-situ forming hydrogels can also be prepared by ionic interactions between polycations and polyanions. For example, Hennink et al. reported on self-gelling hydrogels based on oppositely charged dextran microspheres (Tomme et al., 2005). These charged dextranmicrospheres were prepared by radical polymerization of hydroxyethyl methacrylatederivatized dextran (dex-HEMA) with methacrylic acid (MAA) or dimethylaminoethyl methacrylate (DMAEMA). Hydrogels could be formed as a result of ionic interactions between oppositively-charged microspheres. The networks of hydrogels were disrupted either by applied stress, low pH or high ionic strength. Reversible yield point from rheological analysis indicated that this hydrogel system can be applied for controlled delivery of pharmaceutically active proteins and tissue engineering. However, a main disadvantage of ionically-crosslinked hydrogels is that their mechanical strength is far from satisfactory when they are served as scaffolds for tissue regeneration.
