Fucoidan hydrogels significantly alleviate oxidative stress and enhance the endocrine function of encapsulated beta cells

Microencapsulating pancreatic islets in immunoprotective hydrogels is a promising cellular therapy for type 1 diabetes. However, a major factor limiting the encapsulated islet efficacy is inflammatory/hypoxia mediated oxidative stress, resulting in impaired insulin secretion and ultimately islet cell death. Fucoidan, a natural polysaccharide, possess strong anti-oxidant properties but its effects on beta cells and encapsulation is unknown. Here, we assessed the anti-oxidant effect of fucoidan on beta cells and its effect on encapsulated beta cell viability and function, using fucoidans extracted from two different seaweeds, namely Fucus vesiculosus (FF) and Ascophyllum nodosum (FA). FF exhibited significantly higher total antioxidant capacity and free radical scavenging activity, significantly alleviating intracellular oxidative stress in INS1E beta cells, when compared to FA. In presence of high glucose, FF fucoidans significantly increased insulin secretion both in a dose- and time-dependent manner. Viability, ATP levels and high-glucose responsiveness of rat islets encapsulated in fucoidan-containing hydrogel (Fucogel) microcapsules were significantly higher compared to those encapsulated in pure alginate microcapsules. Similar results were obtained with INS1E pseudo-islets and neonatal pig islets. Fucogels can provide a redox-modulatory niche and an immune barrier in the same time, presenting as an outstanding biomaterial for bioengineered immunoprotective beta cell replacement devices.