Schiff base, an important family of reaction in click chemistry, has received significant attention in the formation of self-healing hydrogels in recent years. Schiff base reversibly reacts even in mild conditions, which allows hydrogels with self-healing ability to recover their structures and functions after damages. Moreover, pH-sensitivity of the Schiff base offers the hydrogels response to biologically relevant stimuli. Different types of Schiff base can provide the hydrogels with tunable mechanical properties and chemical stabilities. In this review, we summarized the design and preparation of hydrogels based on various types of Schiff base linkages, as well as the biomedical applications of hydrogels in drug delivery, tissue regeneration, wound healing, tissue adhesives, bioprinting, and biosensors.

Conductive hydrogel, with electroconductive properties and high water content in a three-dimensional structure is prepared by incorporating conductive polymers, conductive nanoparticles, or other conductive elements, into hydrogel systems through various strategies. Conductive hydrogel has recently attracted extensive attention in the biomedical field. Using different conductivity strategies, conductive hydrogel can have adjustable physical and biochemical properties that suit different biomedical needs. The conductive hydrogel can serve as a scaffold with high swelling and stimulus responsiveness to support cell growth in vitro and to facilitate wound healing, drug delivery and tissue regeneration in vivo. Conductive hydrogel can also be used to detect biomolecules in the form of biosensors. In this review, we summarize the current design strategies of conductive hydrogel developed for applications in the biomedical field as well as the perspective approach for integration with biofabrication technologies.

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Electroconductive hydrogels and scaffolds have great potential for strain sensing and in tissue engineering. Herein, we designed electroconductive self-healing hydrogels and shaperecoverable scaffolds with injectability, strain/motion-sensing ability, and neural regeneration capacity. The crosslinked network of hydrogels and scaffolds was synthesized and prepared under physiological conditions from N-carboxyethyl chitosan (CEC), a chitosan-modified polypyrrole (DCP) nanoparticle (∼40 nm), and a unique aldehyde-terminated difunctional polyurethane (DFPU) crosslinker. CEC was mixed with DCP by electrostatic interaction and then crosslinked with DFPU through a dynamic Schiff base reaction. Schiff base endowed the hydrogels with self-healing behavior, confirmed by rheological examinations. Shape-recoverable scaffolds were obtained by freeze-drying the hydrogels. These hydrogels and scaffolds showed injectability and conductivity (3− 6 mS/cm), while the scaffolds also exhibited high water absorption and durable elasticity after repeated deformation. The hydrogels and scaffolds promoted the attachment, proliferation, and differentiation of neural stem cells (NSCs). The scaffolds had excellent strain/motion-sensing properties in vitro and ex vivo as well as biodegradability and biocompatibility in vivo. Moreover, the neural regeneration capacity of the conductive hydrogel or the cell-laden conductive hydrogel was demonstrated by the rescue of motor function (∼53 and ∼80% functional recoveries, respectively) in the zebrafish brain injury model. These hydrogels and scaffolds are potential candidates for nerve repair and motion sensing.

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