In situ forming biodegradable hydrogels and their application for protein delivery

Hydrogels have been widely applied for biomedical applications, such as protein delivery and tissue engineering, due to their similarity with the extracellular matrix. Hydrogels are water-swollen, insoluble polymer networks. Their high water content renders them compatible with living tissue and proteins and their rubbery nature minimizes damage to the surrounding tissue. Conventionally, hydrogels are preformed and implanted in the body. More recently, hydrogels have been formed in situ under physiological conditions by mixing liquid precursors. These hydrogels are preferred over preformed hydrogels, since cells and bioactive compounds may be easily mixed with the precursor solutions prior to gelation. Moreover, in situ gelation allows for minimally invasive surgery and for the preparation of complex shapes. Hydrogels are formed by physical or chemical crosslinking. Physical crosslinks are formed by noncovalent interactions, such as hydrophobic and ionic interactions and stereocomplexation. Physical crosslinking generally proceeds under mild conditions, thus enabling in situ hydrogel formation and allowing the entrapment of labile compounds. The integrity of physically crosslinked hydrogels may however be lost upon a change in physical conditions. Chemically crosslinked hydrogels are formed by covalent bonds by reaction between functional groups. Most commonly, these hydrogels have been formed by radical chain polymerization of (meth)acrylate derived polymers initiated by photoirradiation. Chemically crosslinked hydrogels are generally more stable than physically crosslinked hydrogels. Chemically crosslinked hydrogels may also be formed in situ. However, care has to be taken that the reactants, products and/or auxiliary compounds are non-toxic.