Adaptable hydrogel with reversible linkages for regenerative medicine: Dynamic mechanical microenvironment for cells

Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix. These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility. It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues. Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix. The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows. First, we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry. Next, we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate, including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling. Finally, we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine. We conclude by discussing the limitations and challenges for adaptable hydrogel, and we present perspectives for future studies.
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Highlights • Introduction of adaptable hydrogels with dynamic mechanical properties as 3D extracellular matrix. • Summary of reversible linkages based on supramolecular interactions and dynamic covalent bonds. • Discussion of how adaptable hydrogels provide dynamic mechanical microenvironment and influence cell behaviors and fate. • Overview of applications of adaptable hydrogel in regenerative medicine.