Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications

The aim of this review was to provide a detailed overview of physical chitosan hydrogels and related networks formed by aggregation or complexation, which are intended for biomedical applications. The structural basis of these systems is discussed with particular emphasis on the network-forming interactions, the principles governing their formation and their physicochemical properties. An earlier review discussing crosslinked chitosan hydrogels highlighted the potential negative influence on biocompatibility of covalent crosslinkers and emphasised the need for alternative hydrogel systems. A possible means to avoid the use of covalent crosslinkers is to prepare physical chitosan hydrogels by direct interactions between polymeric chains, i.e. by complexation, e.g. polyelectrolyte complexes (PEC) and chitosan/poly (vinyl alcohol) (PVA) complexes, or by aggregation, e.g. grafted chitosan hydrogels. PEC exhibit a higher swelling sensitivity towards pH changes compared to covalently crosslinked chitosan hydrogels, which extends their potential application. Certain complexed polymers, such as glycosaminoglycans, can exhibit interesting intrinsic properties. Since PEC are formed by non-permanent networks, dissolution can occur. Chitosan/PVA complexes represent an interesting alternative for preparing biocompatible drug delivery systems if pH-controlled release is n/ot required. Grafted chitosan hydrogels are more complex to prepare and do not always improve biocompatibility compared to covalently crosslinked hydrogels, but can enhance certain intrinsic properties of chitosan such as bacteriostatic and wound-healing activity.