The innate ability of poly(N-isopropylacrylamide) (PNIPAAm) thermo-responsive hydrogel to copolymerize and to graft synthetic polymers and biomolecules, in conjunction with the highly controlled methods of radical polymerization which are now available, have expedited the widespread number of papers published in the last decade—especially in the biomedical field. Therefore, PNIPAAm-based hydrogels are extensively investigated for applications on the controlled delivery of active molecules, in self-healing materials, tissue engineering, regenerative medicine, or in the smart encapsulation of cells. The most promising polymers for biodegradability enhancement of PNIPAAm hydrogels are probably poly(ethylene glycol) (PEG) and/or poly(ε-caprolactone) (PCL), whereas the biocompatibility is mostly achieved with biopolymers. Ultimately, advances in three-dimensional bioprinting technology would contribute to the design of new devices and medical tools with thermal stimuli response needs, fabricated with PNIPAAm hydrogels.

Temperature‐sensitive (thermosensitive) hydrogels, which are part of the family of stimulus‐sensitive hydrogels, consist of water‐filled polymer networks that display a temperature‐dependent degree of swelling. Thermosensitive hydrogels, which can undergo phase transition or swell/de‐swell as temperature changes, have great potential in various technological and biomedical purposes for a number of reasons: their temperature response is reversible, hydrogels are stable and easy to prepare, they can be biocompatible and also be suitably combined with other organic and inorganic materials, resulting in new materials with outstanding properties. Among thermosensitive hydrogels poly(N‐isopropylacrylamide) (PNIPAAm) is the most extensively studied because it brings together the best properties of these materials. Consequently, in the past few years, a wide number of applications and new chemical processes to prepare PNIPAAm and their derivatives are being proposed. The objective of this review is to summarize the fundamentals of thermosensitive hydrogels and recent advances in preparation and both technological and biomedical applications of thermosensitive hydrogel, with a special focus on PNIPAAm and their derivatives. Special attention has been given to the discussion of challenges and future research perspectives based on new horizons not yet considered.