Fucoidan Hydrogels Significantly Alleviate Oxidative Stress and Enhance the Endocrine Function of Encapsulated Beta Cells

Abstract

Microencapsulating pancreatic islets in immunoprotective alginate hydrogels is a promising strategy for treatment of type 1 diabetes. However, this strategy is limited by inflammation and hypoxia mediated oxidative stress, due to encapsulation and the hydrogel itself, leading to impaired insulin secretion and limited short and long term cell survival. Herein, the antioxidant effect of fucoidan, an algae derived polysaccharide, on beta cells, and its positive effects on encapsulated beta cell viability and function is presented. Fucoidan from Fucus vesiculosus (FF) exhibits a high total antioxidant capacity, and free radical scavenging activity, and is able to significantly alleviate intracellular oxidative stress in rat insolinoma beta cells (INS1E). In addition, FF significantly increases insulin secretion in a dose-and time-dependent manner. When FF is incorporated in ultrapure alginate used for microencapsulation of primary rat islets, both viability and glucose responsiveness of rat islets in these socalled Fucogel microcapsules (Fucocaps) are found to be significantly higher compared to islets encapsulated in alginate alone. Similar results are obtained with INS1E pseudoislets and neonatal pig islets. Fucocaps can provide a redox-modulatory niche and an immune barrier for islets and beta cells in the same time leading to significantly improved survival and endocrine function by mitigating oxidative stress.

Comparative Bioactivities of Chemically Modified Fucoidan and λ-Carrageenan toward Cells Encapsulated in Covalently Cross-Linked Hydrogels

“…Most encapsulation studies have utilized complex adhesive proteins or peptides in order to support beta cell survival within hydrogels. ,− In contrast, the present work demonstrates the effectiveness of chemically modified fucoidan-MA to form islet-like spheroids from beta cells within the hydrogel, subsequently maintaining spheroidal morphology and viability over a prolonged period of 32 days. These observations are consistent with those reported previously for unmodified fucoidan polysaccharides, thus confirming that methacrylate modification of fucoidan does not interfere with its ability to facilitate cell survival in a 3D environment when cross-linked with a synthetic polymer.…”

“…Unmodified fucoidan recently has been blended with alginate or other polymers to form physically cross-linked hydrogels or capsules. − However, these systems potentially are subject to high rates of outward diffusion of fucoidan owing to the absence of covalent cross-linking between alginate and fucoidan. The authors of the present work previously examined the cytotoxicity and biological activities of methacrylate-conjugated fucoidan and λ-carrageenan, demonstrating high free radical-scavenging properties and immunomodulatory functionalities .…”

Antioxidant Hydrogels: Antioxidant Mechanisms, Design Strategies, and Applications in the Treatment of Oxidative Stress‐Related Diseases

“…[67][68][69] For example, Reys et al pioneered the development of fucoidan-based alginate hydrogels that encapsulated microencapsulating pancreatic islets for the treatment of diabetes. [45] In this research, fucoidan extracted from Fucus www.advhealthmat.de vesiculosus not only demonstrated high antioxidant capacity but also significantly mitigated intracellular oxidative stress in pancreatic insulinoma beta cells of rats. Furthermore, the fucoidanbased alginate hydrogels could notably enhance islet vitality and increase insulin secretion.…”

“…[188][189][190][191] In contrast to hydrogels incorporated with antioxidants, self-antioxidant hydrogels exhibit superior biocompatibility, stability, and cost-effectiveness. [45,73] However, they have limited room for improvement in antioxidant capacity. On the other hand, hydrogels incorporated with antioxidants allowed the selection of suitable antioxidants based on specific applications and unique antioxidant mechanisms.…”

YAP‐Suppressive Nanodrug Crosslinked Self‐Immunoregulatory Polysaccharide Injectable Hydrogel for Attenuating Cardiac Fibrosis to Treat Myocardial Infarction

“…[21] Fucoidan, a type of natural sulfated polysaccharide mainly composed of L-fucose, has been applied as an inflammation regulator and ROS scavenger in pathological tissues. [22][23][24] The P-selectin expression on human umbilical vein endothelia cells (HUVECs) could be preferably attracted to granulocytes via the interaction between P-selectin and P-selectin glycoprotein ligand-1 (PSGL1). In an inflammatory or hypoxia microenvironment, the expression of P-selectin on HUVECs was highly upregulated.…”