This brief review attempts to summarize research advances in the mechanical toughness and structures of double-network (DN) hydrogels. The focus is to provide a critical and concise discussion on the toughening mechanisms, damage recoverability, stress relaxation, and biomedical applications of tough DN hydrogel systems. Both conventional DN hydrogel with two covalently cross-linked networks and novel DN systems consisting of physical and reversible cross-links are discussed and compared. Covalently cross-linked hydrogels are tough but damage-irreversible. Physically cross-linked hydrogels are damage-recoverable but exhibit mechanical instability, as reflected by stress relaxation tests. This remains one significant challenge to be addressed by future research studies to realize the load-sustaining applications proposed for tough hydrogels. With their special structure and superior mechanical properties, DN hydrogels have great potential for biomedical applications, and many DN systems are now fabricated with 3D printing techniques.

Breast cancer is the most common and biggest health threat for women. There is an urgent need to develop novel breast cancer therapies to overcome the shortcomings of conventional surgery and chemotherapy, which include poor drug efficiency, damage to normal tissues, and increased side effects. Drug delivery systems based on injectable hydrogels have recently gained remarkable attention, as they offer encouraging solutions for localized, targeted, and controlled drug release to the tumor site. Such systems have great potential for improving drug efficiency and reducing the side effects caused by long-term exposure to chemotherapy. The present review aims to provide a critical analysis of the latest developments in the application of drug delivery systems using stimuli-responsive injectable hydrogels for breast cancer treatment. The focus is on discussing how such hydrogel systems enhance treatment efficacy and incorporate multiple breast cancer therapies into one system, in response to multiple stimuli, including temperature, pH, photo-, magnetic field, and glutathione. The present work also features a brief outline of the recent progress in the use of tough hydrogels. As the breast undergoes significant physical stress and movement during sporting and daily activities, it is important for drug delivery hydrogels to have sufficient mechanical toughness to maintain structural integrity for a desired period of time.

Skin wounds are not only an aesthetic concern but also pose great risks to quality of life and general health. As the most promising biomaterial, hydrogels are three-dimensional polymeric networks and have attracted intense research attention. Hydrogels have developed a diverse range of biomedical and biopharmaceutical applications, owing to their large water content, biocompatibility, tunable mechanical properties, and stimuli-responsiveness. Stimuli-responsive hydrogels are smart materials which exhibit gelation, structural, degradation, performance and function changes when treated with external stimulations. Using these hydrogels to prepare wound dressing is a rapidly growing research area and has exhibited encouraging healing outcomes in small animal models, especially for the treatment of chronic wounds, diabetic wounds, and persistent skin inflammations. The present work gives a detailed and critical analysis on the design strategies, gelation mechanisms, materials selection, stimuli-responsiveness, hydrogel degradation, drug release profiles, and treatment outcomes of wound dressings prepared by the hydrogels with sensitivity to temperature, pH, reactive oxygen species (ROS), glucose, enzymes, and lights. We summarize, analyze, and critically evaluate the most recent publications in this area to explain, compare, and assess why and how various synthetic and bio-polymers are utilized by materials scientists to develop the next generation of skin wound dressing and regeneration. Graphical abstract