Fucoidans, sulfated polysaccharides extracted from brown algae, are marine products with the potential to modulate bone formation and vascularization processes. The bioactivity and safety of fucoidans are highly associated with their chemical structure, which may vary with algae species and extraction method. Thus, in depth evaluation of fucoidan extracts in terms of endotoxin content, cytotoxicity, and their detailed molecular biological impact on the individual cell types in bone is needed. In this study, we characterized fucoidan extracts from three different Fucus species including Fucus vesiculosus (Fv), Fucus serratus (Fs), and Fucus distichus subsp. evanescens (Fe) for their chemical features, endotoxin content, cytotoxicity, and bioactive effects on human outgrowth endothelial cells (OEC) and human mesenchymal stem cells (MSC) as in vitro models for bone function and vascularization. Extracts contained mainly high molecular weight (HMW) fucoidans and were free of endotoxins that may cause inflammation or influence vascularization. OEC tolerated fucoidan concentrations up to 200 µg/mL, and no indication of cytotoxicity was observed. The inflammatory response, however, investigated by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and endothelial barrier assessed by impedance measurement differed for the individual extracts. MSC in comparison with endothelial cells were more sensitive to fucoidans and showed partly reduced metabolic activity and proliferation at higher doses of fucoidans. Further results for MSC indicated impaired osteogenic functions in alkaline phosphatase and calcification assays. All tested extracts consistently lowered important molecular mediators involved in angiogenesis, such a VEGF (vascular endothelial growth factor), ANG-1 (angiopoietin 1), and ANG-2 (angiopoietin 2), as indicated by RT-PCR and ELISA. This was associated with antiangiogenic effects at the functional level using selected extracts in co-culture models to mimic bone vascularization processes during bone regeneration or osteosarcoma.

Fucoidans are algal polysaccharides that exhibit protective properties against oxidative stress. The aim of this study was to investigate different fucoidans from brown seaweeds for their ability to protect against iron-dependent oxidative stress (ferroptosis), a main hallmark of retinal and brain diseases, including hemorrhage. We investigated five new high-molecular weight fucoidan extracts from Fucus vesiculosus, F. serratus, and F. distichus subsp. evanescens, a previously published Laminaria hyperborean extract, and commercially available extracts from F. vesiculosus and Undaria pinnatifida. We induced oxidative stress by glutathione depletion (erastin) and H2O2 in four retinal and neuronal cell lines as well as primary cortical neurons. Only extracts from F. serratus, F. distichus subsp. evanescens, and Laminaria hyperborea were partially protective against erastin-induced cell death in ARPE-19 and OMM-1 cells, while none of the extracts showed beneficial effects in neuronal cells. Protective fucoidans also attenuated the decrease in protein levels of the antioxidant enzyme GPX4, a key regulator of ferroptosis. This comprehensive analysis demonstrates that the antioxidant abilities of fucoidans may be cell type-specific, besides depending on the algal species and extraction method. Future studies are needed to further characterize the health-benefiting effects of fucoidans and to determine the exact mechanism underlying their antioxidative abilities.

Background Fucoidans are sulfated polysaccharides from the cell-wall of brown algae. They have a wide range of applications in medicine, including regenerative medicine, ophthalmology, cancer, and autoimmune disease. Biological activity of fucoidans directly depends on their structure, which remains poorly understood. This is primarily because the polymeric nature of these molecules limits the use of nuclear magnetic resonance and mass spectrometry, classical tools of structural biology for their structural characterization. Raman and Infrared spectroscopies are non-invasive and non-destructive techniques that can be used to probe the structural organization of biological specimens. In this study, we investigate the potential of Raman and Infrared spectroscopy for structural analysis of several fucoidan extracts. Results Our results show that Infrared and Raman provide different but complimentary information about the structure of crude extracts of fucoidans, revealing the presence of minor impurities from co-extractants. We also found that at high extraction temperatures acidic conditions limit formation of melanoidins, while also yielding relatively high sulfate ester fucoidan. However, at high temperatures, water extraction may potentially result in formation of advanced glycation end products. Their presence could be problematic for fucoidan extracts intended for medicinal use, as advanced glycation end products have been linked to endocrine interruption mechanisms in vivo by crosslinking to and permanently altering extracellular matrix proteins. Conclusion Raman and Infrared can be used as complementary tools for rapid screening of crude fucoidan extracts, which can be a valuable tool for assessing impurities that remain after extraction.

The need for a substitute for allograft and autograft is rising as bone graft surgeries exceed available supplies. We investigated the efficacy of the low‐molecular weight marine bioactive compound fucoidan (FUC) on bone regeneration and implant fixation in seven female sheep, as FUC has shown great promise as a bone substitute. Titanium implants were inserted bilaterally in the distal femurs to test three hydroxyapatite/fucoidan (HA/FUC) groups and compared to allograft. The HA was coated with either 500 or 1500 μg of FUC, obtained by microwave‐assisted chemical extraction, or 500 μg of FUC obtained by an enzyme‐assisted extraction method. The concentric 2‐mm gap around the implant was filled with either one of the HA/FUCs or allograft from the donor sheep. After 12 weeks, implant–bone blocks were harvested and divided into three parts for mechanical push‐out testing, immunohistochemistry, and micro‐CT and histomorphometry. Pronounced bone formations were observed by micro‐CT and histomorphometry in all groups, but higher bone volume fractions were seen in the allograft group compared to the three HA/FUC groups. The trabecular thickness, trabecular separation, and architectural anisotropy were all significantly higher in the allograft group compared to the three HA/FUC groups. In conclusion, adequate bone formation was observed in all groups, although the bone formation was significantly greater in the allograft group. Also, no significant differences existed in the shear mechanical properties between groups, suggesting that the combination of HA and FUC can achieve a similar fixation strength to allograft in this model.

Fucoidans, sulphated polysaccharides from brown algae, are a group of heterogeneous biopolymers. Located in the brown algae cell wall, they cross-link to cellulose microfibrils, protecting the algae cells against mechanical and chemical stress at sea (Deniaud-Bouët et al., 2014). Several studies report the many bioactivities they exert in vitro, such as anti-cancer (Anastyuk et al., 2012), anti-inflammatory (Cumashi et al., 2007), anti-viral and immuno-regulatory (Sun et al., 2018. Their diverse bioactivity enables their use in many industrial applications in both the food industry and in medicine and pharmaceuticals, including the field of tissue engineering (Silva et al.,