A review on thermoresponsive PNIPAM hydrogels for regenerative medicine: from mechanical design to tissue adhesion

Abstract Poly(N-isopropylacrylamide) (PNIPAM) hydrogels are potential wound dressings due to their lower critical solution temperature (LCST) of 32°C, close to physiological temperature, enabling injectable or spreadable formulations that quickly form a gel on irregular wounds while withstanding tissue motion. These systems aim to balance skin-like mechanical integrity, strong dry and wet adhesion and deliver stability after placement. This review summarizes the impact of the LCST driven phase transition on water content, pore structure, stiffness and interfacial hydration and how these effects regulate adhesion strength and failure mode. It compares major mechanical reinforcement strategies in PNIPAM-based dressings including hybrid nanocomposites, double network architectures, dynamic or sacrificial crosslinking strategies that enhance toughness, stretchability and recovery. It also describes multifunctional systems incorporating antibacterial activity, hemostasis, sensing, photothermal response or controlled drug release with emphasis on their effect on mechanics and adhesion. Since adhesion in soft hydrogels is strongly correlated with viscoelastic behavior, the review identifies rheological measures (G′/G″ trends, shear thinning, yield behavior and recovery) as measures of injectability and wet adhesion stability. Lastly, essential translational barriers are defined, including limited biodegradability, additive cytotoxicity, sterilization, durability in exudate and motions and standardized testing and reporting to facilitate reliable comparison and clinical relevance.