Thermal Phase Behavior of PNIPAM-Based Hydrogels: Different Scenarios and Implications in Injectable Hydrogel Design

Poly(N-isopropylacrylamide) (PNIPAM)-based hydrogels are "smart" materials of great interest and demand, primarily in a variety of biomedical applications, due to their LCST close to physiological temperature. The basic biomedical applications of PNIPAM-based injectable hydrogels include controlled drug delivery, tissue engineering, wound healing, and cancer therapy. This review summarizes the thermal phase behavior of PNIPAM-based systems under different conditions, including different scenarios of physical gelation in polymer solutions and volume phase transitions in chemically crosslinked hydrogels. The thermodynamics of the coil-to-globule phase transition, its relation to gel formation, and mechanisms underlying the phase transitions in PNIPAM-based hydrogels are discussed, as well as external parameters which may affect these processes. Different types of phase diagrams observed for PNIPAM-based systems are considered, with particular attention paid to the cases in which gelation occurs separately from the coil-to-globule transition. The rational design of injectable platforms should be based upon a thorough understanding of the PNIPAM-based system's phase behavior to achieve controllable and reproducible properties.