Injectable and self-healing fucoidan hydrogel: A natural anti-inflammatory biomaterial.

Fucoidan, a natural sulfated polysaccharide, offers immense potential as a natural immune-modulatory bioactive polymer to develop hydrogels for tissue engineering. Yet, systematically tunable hydrogels composed primarily of fucoidan, that can also be injected into target tissues to reduce inflammation are still lacking. To address this, we have developed a highly tunable, hydrazone crosslinked fucoidan (hcFu) hydrogel that is injectable and can be utilized for various tissue engineering applications. We demonstrate that chemically modified fucoidan retains its ability to induce macrophage polarization. The hcFu hydrogel can be tuned to achieve gelation rate from instantaneous to over 10 min. Moreover, due to the dynamic nature of hydrazone covalent bonds, fucoidan hydrogel displays viscoelasticity, self-healing, extrudability, injectability, and excellent stability in physiological environments. In-vitro biocompatibility assays confirm its capacity to support cell growth, while in-vitro and in-vivo studies reveal its inherent anti-inflammatory and antioxidant effects. Importantly, hcFu hydrogel effectively modulates immune responses without incorporating additional cytokines. These findings position fucoidan hydrazone as a promising natural anti-inflammatory biomaterial with significant potential for tissue engineering and therapeutic applications.