Shaped stimuli-responsive hydrogel particles: syntheses, properties and biological responses

The ability to create nano- and micro-sized hydrogel matrices of well-defined shapes can provide a powerful means not only to mimic the key properties of biological systems, but also to regulate shape-dependent particle biodistribution and cellular association, and to correspondingly optimize drug delivery carriers. This review focuses on stimuli-responsive hydrogel particles of non-spherical shapes ranging from filled porous networks to hollow capsules. We summarize a pool of current experimental approaches and discuss perspectives in the development of the synergistic combination of shape and stimuli-response in particulate hydrogels. Recent advances in the design and synthesis of the pH-, redox-, temperature-sensitive, mechanical force-, magnetic- and enzyme-responsive hydrogel particles of non-spherical shapes are presented. Examples of existing and emerging technologies for creating a variety of shapes with controlled hydrogel composition and size are highlighted. We also discuss the effects of shape on the physiochemical properties of these particles as well as their shape-regulated biological interactions including particle circulation time and biodistribution.