Advances in Dual-Crosslinking Strategies for Hydrogels: From Physical-Chemical Synergy to Stimuli-Responsive Control

Abstract

Population aging and the rising burden of trauma and chronic disease have increased the demands placed on biomedical hydrogels. In addition to biocompatibility, these materials are expected to provide mechanical support, processability, and environmental responsiveness. A single crosslinked network rarely balances all of these requirements. Dual-crosslinked networks, which combine reversible physical interactions with stable chemical bonds, have therefore received increasing attention. This review examines the network-forming mechanisms of dual-crosslinked hydrogels, with emphasis on how crosslinking density, degree of oxidation, and energy-dissipation structures affect mechanical behavior. Strategies for pH-, temperature-, light-, and redox-responsive functions and the corresponding characterization methods are also summarized. Available studies indicate that a suitable combination of two crosslinking mechanisms can improve strength, toughness, and tissue adhesion while retaining injectability, self-healing, and stimulus responsiveness to varying degrees. We further discuss translational barriers, including degradation-rate matching, coupling among performance parameters, and scale-up. This review is intended to support the structural design of hydrogels for tissue regeneration, drug delivery, and flexible bioelectronics.