Pre‐clinical and clinical applications of thermoreversible hydrogels in biomedical engineering: a review

Thermoreversible polymer hydrogels (TRGs) are physical aqueous networks triggered by temperature, that find potential applications in tissue engineering (TE) and drug/gene delivery. When systems with lower critical solution temperature (LCST) behaviour are used, the aqueous solution of polymer is mixed with cells or drugs/genes, depending on the desired application, at room temperature and then injected in vivo to form a hydrogel. This in-situ forming hydrogel acts as a matrix for tissue regeneration or controlled and targeted release of the compound. This review focuses on discussing the studies in which synthetic TRGs with LCST behaviour have been applied in vivo in model animals. These studies are categorised depending on the general structure of the polymer, as follows: i) poloxamer (also known as Pluronics®), ii) degradable polymers, iii) poly(N-isopropylacrylamide) (PNIPAAm), iv) poly(organophosphazene), and v) poly(2-ethyl-2-oxazoline). In general, when the system is optimised, TRGs provide sustained and topical release of the drugs, thus minimising the undesired side effects. When applied in the TE field, tissue formation was observed. Interestingly, two polymers have reached clinical trials, namely poloxamer 407 (P407, Pluronic® F127, often combined with P188, F68), and Regel® (the formulation of Regel® with the anticancer agent paclitaxel is known as Oncogel®), indicating the challenges need to be overcome before successful application in clinics