Thermoresponsive polysaccharides and their thermoreversible physical hydrogel networks

Abstract

Thermoresponsive polymers have been used extensively for various applications including food additives, pharmaceutical formulations, therapeutic delivery, cosmetics and environmental remediation, to mention a few. Many thermoresponsive polymers have the ability to form physical hydrogel networks in response to temperature changes, which are particularly useful for emerging biomedical applications, including cell therapies, drug delivery systems, tissue engineering, wound healing and 3D bioprinting. In particular, the use of polysaccharides with thermoresponsive properties has been of interest due to their wide availability, versatile functionality, biodegradability, and in many cases, inherent biocompatibility. Naturally thermoresponsive polysaccharides include agarose, carrageenans and gellan gum, which exhibit upper critical solution temperatures, transitioning from a solution to a gel state upon cooling. Arguably, this limits their use in biomedical applications, particularly for cell encapsulation as they require raised temperatures to maintain a solution state that may be detrimental to living systems. Conversely, significant progress has been made over recent years to develop synthetically modified polysaccharides, which tend to exhibit lower critical solution temperatures, transitioning from a solution to a gel state upon warming. Of particular interest are thermoresponsive polysaccharides with a lower critical solution temperature in between room temperature and physiological temperature, as their solutions can conveniently be manipulated at room temperature before gelling upon warming to physiological temperature, which makes them ideal candidates for many biological applications. Therefore, this review provides an introduction to the different types of thermoresponsive polysaccharides that have been developed, their resulting hydrogels and properties, and the exciting applications that have emerged as a result of these properties.