Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anti-cancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10–50 kDa), medium (MMW, 50–100 kDa) and high (HMW, >100 kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had the highest levels of sugars, acids and sulphation among molecular weight fractions. There was a dose-dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in the sub-G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress-induced apoptosis-like cell death for F. vesiculosus fucoidan and features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.

Mesenchymal stem cells play a vital role in bone formation process by differentiating into osteoblasts, in a tissue that offers not a flat but a discontinuous three-dimensional (3D) topography in vivo. In order to understand how geometry may be affecting mesenchymal stem cells, this study explored the influence of 3D geometry on mesenchymal stem cell-fate by comparing cell growth, viability and osteogenic potential using monolayer (two-dimensional, 2D) with microsphere (3D) culture systems normalised to surface area. The results suggested lower cell viability and reduced cell growth in 3D. Alkaline phosphatase activity was higher in 3D; however, both collagen and mineral deposition appeared significantly lower in 3D, even after osteogenic supplementation. Also, there were signs of patchy mineralisation in 3D with or without osteogenic supplementation as early as day 7. These results suggest that the convex surfaces on microspheres and inter-particulate porosity may have led to variable cell morphology and fate within the 3D culture. This study provides deeper insights into geometrical regulation of mesenchymal stem cell responses applicable for bone tissue engineering.

Phosphate-based glasses (PBGs) are biomaterials that degrade under physiological conditions and can be modified to release various ions depending on end applications. This study utilized slow-degrading (P45:45P₂O₅-16CaO-24MgO-11Na₂O-4Fe₂O₃, mol %) and comparatively faster degrading (P40:40P₂O₅-16CaO-24MgO-20Na₂O, mol %) PBG microspheres with or without porosity, to evaluate the combined effect of chemical formulation and geometry on human mesenchymal stem cells (MSCs), a clinically relevant cell source for orthopedic applications. Scanning electron microscopy showed 2, 46, and 29% of P45 bulk (P45-B), P40 bulk (P40-B), and P40 porous (P40-P) microspheres, respectively, that had cracks or peeling off surfaces after 42 days of incubation in culture medium. Cytotoxicity assessment showed that glass debris released into the culture medium may interact with cells and affect their survival. Direct-contact cell experiments up to 42 days showed that P45-B microspheres did not sustain viable long-term cell cultures and did not facilitate extracellular matrix formation. On the other hand, P40-B microspheres enhanced alkaline phosphatase activity, calcium deposition, and collagen and osteocalcin production in MSCs. Introduction of porosity in P40 glass further enhanced these parameters and proliferation at later time points. The small pore windows (<5 μm wide) and interconnection (<10 μm wide) may have allowed limited cell penetration into the porous structures. P40-B and P40-P have potential for bone repair and reinforcement therapy based on their chemical formulation and porous geometry.