Functional Tough Hydrogels: Design, Processing, and Biomedical Applications

Conspectus Hydrogels are high-water-content soft materials with widely tunable physicochemical properties, resembling soft tissues. Tremendous progress in engineering hydrogels with good biocompatibility, suitable bioactivities, and controlled geometries has made them promising candidates for broad applications. Nevertheless, conventional hydrogels usually suffer from weak mechanical properties, limiting their use in biomedical settings involving load-bearing and persistent mechanical deformations. Inspired by the extreme mechanical properties and multiscale hierarchical structures of biological tissues, mechanically robust tough hydrogels have been developed. Combining robust mechanical properties and other desired performance characteristics in functional tough hydrogels expands their opportunities in biomedical fields. This Account seeks to guide the readership regarding the recent progress in functional tough hydrogels with a focus on molecular/structural design and novel fabrications, particularly surrounding the works reported by our groups. Meanwhile, functional tough hydrogels for multiple biomedical applications are discussed, highlighting the underlying mechanisms governing their relevant applications. We begin by introducing the definition, measurements, and design principles of tough hydrogels and hydrogel adhesives in terms of soft materials mechanics. Various molecular and structural engineering approaches by building mechanical dissipation into stretchable hydrogels to realize stress homogenization or energy dissipation are exploited to fabricate tough hydrogels. Molecular engineering-based network architecture design of homogeneous hydrogels and structural engineering-based design of heterogeneous hydrogels are elaborated. The conventional energy-dissipation-based tough hydrogels are reinforced by the sacrificial bonds or components, leading to a substantial toughness reduction in subsequent loading cycles. To this end, new molecular designs, including highly entangled hydrogels and sliding-ring hydrogels, have been developed to resolve the toughness–hysteresis conflict. In addition, novel processing techniques, including salting out, freeze casting, and three-dimensional (bio)printing, are exploited to manipulate the multiscale structures and geometries for tough hydrogel fabrication. As some of the most actively studied materials in recent years, functional tough hydrogels are finding promising applications as bioadhesives/coatings, tissue-engineering scaffolds, soft robot/actuators, and bioelectronics interfaces. The development of tough bioadhesives/coatings lies in constructing strong interfacial linkages between the tough hydrogels and the underlying substrates, having broad applications in wound closure and drug delivery. Tough hydrogels have also been widely studied for use in tissue engineering and regenerative medicine, although the conflict of mechanical robustness–cellular function restricts their practical applications. The flexible and compliant tough hydrogels with stimuli-responsive shape shifting and pressure-triggered actuation make them good candidates as actuators and soft robots for biomedical devices dealing with soft tissues. Conductive tough hydrogels also have been widely exploited for utility in bioelectronics. In the end, we highlight the major challenges and emphasize the trends in developing the next-generation functional tough hydrogels for practical biomedical and medical applications.