The Thermogel Chronicle─From Rational Design of Thermogelling Copolymers to Advanced Thermogel Applications

ConspectusTemperature responsive supramolecular hydrogels, also known as thermogels, are produced by the self-assembly of amphiphilic copolymers in solution following temperature stimulus. They are a class of high caliber novel materials possessing highly attractive properties such as injectability, ability to undergo temperature controlled reversible sol–gel phase transitions, high biocompatibility, and tunable biodegradability. Much research vigor has been dedicated to designing advanced amphiphilic copolymers and investigating their molecular interactions in order to enhance the properties of the thermogelling systems and expand the scope of their applications. As such, thermogelling systems have since become well established in the field of sustained localized drug or protein delivery and have also been demonstrated as high potential materials for niche applications such as three-dimensional cell culture, wound healing patches, and vitreous endotamponades. Recent developments saw the advent of thermogelling systems with advanced biomedical applications ranging from enhanced cancer therapy to radiology imaging to tissue engineering, and these are usually achieved by the conjugating of biologically relevant molecules such as drugs and peptides to the thermogel copolymer or by incorporating nanoparticles into the thermogel systems. New developments in this field see a shift away from employing traditional synthetic polymers such as polypropylene glycol (PPG) and poly(lactic-co-glycolic acid) (PLGA) to utilizing more advanced nature-derived bioactive molecules and also introducing chiral moieties in the thermogelling copolymer backbone.There are currently a few main types of thermogel copolymers such as diblock, triblock, end-capped, graft, and random multiblock polyurethane thermogels. Among these, our lab is specialized in the synthesis and application of polyurethane multiblock thermogels. These thermogels have the advantage of high molecular weights and enhanced intermolecular hydrogen bonding arising from the urethane groups. These generally allow for the formation of thermogelling systems with higher gel stiffness, resilience, and encapsulation efficiency, allowing these polyurethane thermogels to be well suited for niche applications such as sustained drug delivery and vitreous endotamponades. In this Account, we summarize the fundamental polymeric factors influencing the micellar and bulk polyurethane thermogel properties, provide our group’s insights into the rational design of these thermogels for various advanced applications and finally discuss the future possibilities of thermogelling systems. We speculate that there is still much untapped potential of thermogels in the biomedical field and these can possibly be achieved by designing thermogel copolymers with bioactive moieties and exploring more advanced branched architectures. In addition, we also propose the expansion of thermogels beyond biomedical fields, for which our lab has demonstrated thermogels as electrode contacts for noninvasive plant health monitoring.