Dynamic protein and polypeptide hydrogels based on Schiff base co-assembly for biomedicine

Abstract

Stimuli-responsive biopolymer hydrogels are promising building blocks for biomedical devices, attributable to their excellent hydrophilicity, biocompatibility, and dynamic responsiveness to temperature, light, pH, and water content. Although hydrogels find interesting applications as drug carriers, therapeutic adhesives, scaffolds for tissue engineering, inks for bioprinting, and biosensors, conventional chemically crosslinked hydrogels often lack adaptive and biomimetic properties needed for diverse biomedical applications. Using dynamic and reversible crosslinks such as the Schiff base bond, biomimetic hydrogels featuring structurally dynamic behaviours, such as shape memory, self-healing properties, and dynamic mechanical resilience, can be developed for in vivo therapy. Natural proteins and polypeptides are non-toxic, biodegradable, and biocompatible biopolymers that serve fundamental structural and biochemical functions in the human body. Besides natural polypeptides, easily processible synthetic polypeptides are protein analogues with widely tunable sequences that form secondary structures. Therefore, natural proteins and synthetic polypeptides are excellent candidates for fabricating Schiff base-linked biomedical hydrogels. This review outlines the functional properties, design approaches, and applications of Schiff base-linked protein and polypeptide hydrogels in tissue engineering, regenerative medicine, wound dressing, drug delivery, bioprinting, and biosensors. The review ends with an outlook of future developments for potential applications of Schiff base-linked protein and polypeptide hydrogels in and beyond biomedicine.