Imine Crosslinked, Injectable, and Self‐Healing Fucoidan Hydrogel with Immunomodulatory Properties

Abstract Biomaterials with inherent anti‐inflammatory properties and the ability to foster a pro‐regenerative environment hold significant promise for enhancing cell transplantation and tissue regeneration. Fucoidan, a sulfated polysaccharide with well‐documented immune‐regulatory and antioxidant capabilities, offers strong potential for creating such biomaterials. Yet, there is a lack of engineered fucoidan hydrogels that are injectable and provide tunable physicochemical properties. In this study, the ability of fucoidan to undergo periodate‐mediated oxidation is leveraged to introduce aldehydes into backbone (oxidized fucoidan, OFu), enabling the formation of reversible, imine‐crosslinks with amine‐containing molecules such as gelatin. The imine‐crosslinked OFu‐gelatin hydrogel provided excellent control over gelation rate and mechanical properties. Counter‐intuitively, OFu‐gelatin hydrogel exhibited excellent long‐term stability (≥28 days), even though imine crosslinks are known to be relatively less stable. Moreover, the OFu‐gelatin hydrogels are self‐healing, injectable, and biocompatible, supporting cell culture and encapsulation. Furthermore, fucoidan hydrogels displayed immune‐modulatory properties both in vitro and in vivo. This innovative injectable fucoidan hydrogel presents a versatile platform for applications in tissue engineering and regenerative medicine.