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

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.