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Background/Objectives: Sodium alginate reduces appetite and glycemia, when consumed in water- and sugar-based drinks. But, its effects when added to other commonly consumed beverages have not been reported. Because chocolate milk (CM) is criticized for raising blood glucose more than unflavored milk, the aim of our study was to investigate the effect of adding a strong-gelling sodium alginate to CM on glycemia, insulinemia, appetite and food intake. Subjects/Methods: In a randomized crossover design, 24 men (22.9±0.4 years; 22.5±0.3 kg/m 2 ) were provided with isovolumetric (325 ml) treatments of CM, 1.25% alginate CM, 2.5% alginate CM or 2.5% alginate solution. Sodium alginate had a ratio of 0.78:1 of mannuronic acid (M) to guluronic acid (G) residues, and was block distributed. Treatments were standardized for lactose, sucrose and calcium content, and provided 120 min before an ad libitum pizza meal during which food intake was measured. Appetite and blood glucose and insulin were measured at baseline and at intervals pre- and post-meal. Results: Addition of 2.5% alginate to CM reduced peak glucose concentrations, at 30 min, by an average of 6% and 13% compared with 1.25% alginate CM (95% confidence intervals (CIs): 0.02–1.08; P =0.037) and CM alone (95% CIs: 0.49–1.55; P =0.000) respectively. Insulin peaks at 30 min were lower by 46% after 2.5% alginate CM relative to CM (95% CIs: 3.49–31.78; P =0.009). Pre-meal appetite was attenuated dose dependently by alginate addition to CM; CM with 2.5% alginate reduced mean appetite by an average of 134% compared with CM alone (95% CIs: 8.87–18.98; P =0.000). However, total caloric intake at the pizza meal did not differ among treatments. Conclusions: The addition of a strong-gelling sodium alginate to CM decreases pre-meal glycemia, insulinemia and appetite, but not caloric intake at a meal 2 h later, in healthy adult men.

Advances in nanotechnology have demonstrated potential application of nanoparticles (NPs) for effective and targeted drug delivery. Here we investigated the antimicrobial and immunological properties and the feasibility of using NPs to deliver antimicrobial agents to treat a cutaneous pathogen. NPs synthesized with chitosan and alginate demonstrated a direct antimicrobial activity in vitro against Propionibacterium acnes, the bacterium linked to the pathogenesis of acne. By electron microscopy (EM) imaging, chitosan–alginate NPs were found to induce the disruption of the P. acnes cell membrane, providing a mechanism for the bactericidal effect. The chitosan–alginate NPs also exhibited anti-inflammatory properties as they inhibited P. acnes-induced inflammatory cytokine production in human monocytes and keratinocytes. Furthermore, benzoyl peroxide (BP), a commonly used antiacne drug, was effectively encapsulated in the chitosan–alginate NPs and demonstrated superior antimicrobial activity against P. acnes compared with BP alone while demonstrating less toxicity to eukaryotic cells. Together, these data suggest the potential utility of topical delivery of chitosan–alginate NP-encapsulated drug therapy for the treatment of dermatologic conditions with infectious and inflammatory components.

Self-healing injectable hydrogels can be formulated as three-dimensional carriers for the treatment of neurological diseases with desirable advantages, such as avoiding the potential risks of cell loss during injection, protecting cells from the shearing force of injection. However, the demands for biocompatible self-healing injectable hydrogels to meet above requirements and to promote the differentiation of neural stem cells (NSCs) into neurons remain a challenge. Herein, we developed a biocompatible self-healing polysaccharide-based hydrogel system as a novel injectable carrier for the delivery of NSCs. N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OSA) are the main backbones of the hydrogel networks, denoted as CEC-l-OSA hydrogel (“l” means “linked-by”). Owing to the dynamic imine cross-links formed by a Schiff reaction between amino groups on CEC and aldehyde groups on OSA, the hydrogel possesses the ability to self-heal into a integrity after being injected from needles under physiological conditions. The CEC-l-OSA hydrogel in which the stiffness mimicking nature brain tissues (100~1000 Pa) can be finely tuned to support the proliferation and neuronal differentiation of NSCs. The multi-functional, injectable, and self-healing CEC-l-OSA hydrogels hold great promises for NSC transplantation and further treatment of neurological diseases.

The objective was to determine the effects of dietary fibre with bulking, viscous and gel-forming properties on satiation, and to identify the underlying mechanisms. We conducted a randomised crossover study with 121 men and women. Subjects were healthy, non-restrained eaters, aged 18–50 years and with normal BMI (18·5–25 kg/m 2 ). Test products were cookies containing either: no added fibre (control), cellulose (bulking, 5 g/100 g), guar gum (viscous, 1·25 g/100 g and 2·5 g/100 g) or alginate (gel forming, 2·5 g/100 g and 5 g/100 g). Physico-chemical properties of the test products were confirmed in simulated upper gastrointestinal conditions. In a cinema setting, ad libitum intake of the test products was measured concurrently with oral exposure time per cookie by video recording. In a separate study with ten subjects, 4 h gastric emptying rate of a fixed amount of test products was assessed by 13 C breath tests. Ad libitum energy intake was 22 % lower for the product with 5 g/100 g alginate (3·1 ( sd 1·6) MJ) compared to control (4·0 ( sd 2·2) MJ, P < 0·001). Intake of the other four products did not differ from control. Oral exposure time for the product with 5 g/100 g alginate (2·3 ( sd 1·9) min) was 48 % longer than for control (1·6 ( sd 0·9) min, P = 0·01). Gastric emptying of the 5 g/100 g alginate product was faster compared to control ( P < 0·05). We concluded that the addition of 5 g/100 g alginate (i.e. gel-forming fibre) to a low-fibre cookie results in earlier satiation. This effect might be due to an increased oral exposure time.

Hyperthermia is one of the promising treatments for cancer therapy. However, the development of a magnetic fluid agent that can selectively target a tumor and efficiently elevate temperature while exhibiting excellent biocompatibility still remains challenging. Here a new core-shell nanostructure consisting of inorganic iron oxide (Fe3O4) nanoparticles as the core, organic alginate as the shell, and cell-targeting ligands (ie, D-galactosamine) decorated on the outer surface (denoted as Fe3O4@Alg-GA nanoparticles) was prepared using a combination of a pre-gel method and coprecipitation in aqueous solution. After treatment with an AC magnetic field, the results indicate that Fe3O4@Alg-GA nanoparticles had excellent hyperthermic efficacy in a human hepatocellular carcinoma cell line (HepG2) owing to enhanced cellular uptake, and show great potential as therapeutic agents for future in vivo drug delivery systems.

Prospecting macroalgae (seaweeds) as feedstocks for bioconversion into biofuels and commodity chemical compounds is limited primarily by the availability of tractable microorganisms that can metabolize alginate polysaccharides. Here, we present the discovery of a 36—kilo—base pair DNA fragment from Vibrio splendidus encoding enzymes for alginate transport and metabolism. The genomic integration of this ensemble, together with an engineered system for extracellular alginate depolymerization, generated a microbial platform that can simultaneously degrade, uptake, and metabolize alginate. When further engineered for ethanol synthesis, this platform enables bioethanol production directly from macroalgae via a consolidated process, achieving a titer of 4.7% volume/volume and a yield of 0.281 weight ethanol/weight dry macroalgae (equivalent to ~80% of the maximum theoretical yield from the sugar composition in macroalgae).

Variations in a multitude of material microenvironmental properties have been observed across tissues in vivo, and these have profound effects on cell phenotype. Phenomenological experiments have suggested that certain of these features of the physical microenvironment, such as stiffness, could sensitize cells to other features; meanwhile, mechanistic studies have detailed a number of biophysical mechanisms for this sensing. However, the broad molecular consequences of these potentially complex and nonlinear interactions bridging from biophysical sensing to phenotype have not been systematically characterized, limiting the overall understanding and rational deployment of these biophysical cues. Here, we explore these interactions by employing a 3D cell culture system that allows for the independent control of culture substrate stiffness, stress relaxation, and adhesion ligand density to systematically explore the transcriptional programs affected by distinct combinations of biophysical parameters using RNA-seq. In mouse mesenchymal stem cells and human cortical neuron progenitors, we find dramatic coupling among these substrate properties, and that the relative contribution of each property to changes in gene expression varies with cell type. Motivated by the bioinformatic analysis, the stiffness of hydrogels encapsulating mouse mesenchymal stem cells was found to regulate the secretion of a wide range of cytokines, and to accordingly influence hematopoietic stem cell differentiation in a Transwell coculture model. These results give insights into how biophysical features are integrated by cells across distinct tissues and offer strategies to synthetic biologists and bioengineers for designing responses to a cell’s biophysical environment.

Alginate, a natural acidic polysaccharide extracted from marine brown seaweeds, is composed of different blocks of β-(1, 4)-D-mannuronate (M) and its C-5 epimer α-(1, 4)-L-guluronate (G). Alginate-derived guluronate oligosaccharide (GOS) readily activates macrophages. However, to understand its role in immune responses, further studies are needed to characterize GOS transport and signalling. Our results show that GOS is recognized by and upregulates Toll-like receptor 4 (TLR4) on RAW264.7 macrophages, followed by its endocytosis via TLR4. Increased expression of TLR4 and myeloid differentiation protein 2 (MD2) results in Akt phosphorylation and subsequent activation of both nuclear factor-κB (NF-κB) and mechanistic target of rapamycin (mTOR). Moreover, GOS stimulates mitogen-activated protein kinases (MAPKs); notably, c-Jun N-terminal kinase (JNK) phosphorylation depends on TLR4 initiation. All these events contribute to the production of inflammatory mediators, either together or separately. Our findings also reveal that GOS induces cytoskeleton remodelling in RAW264.7 cells and promotes macrophage proliferation in mice ascites, both of which improve innate immunity. Conclusively, our investigation demonstrates that GOS, which is dependent on TLR4, is taken up by macrophages and stimulates TLR4/Akt/NF-κB, TLR4/Akt/mTOR and MAPK signalling pathways and exerts impressive immuno-stimulatory activity.

Incorporating therapeutic genes into three-dimensional biomaterials is a promising strategy for enhancing tissue regeneration. Alginate hydrogels have been extensively investigated for cartilage and bone tissue engineering, including as carriers of transfected cells to sites of injury, making them an ideal gene delivery platform for cartilage and osteochondral tissue engineering. The objective of this study was to develop gene-activated alginate hydrogels capable of supporting nanohydroxyapatite (nHA)-mediated nonviral gene transfer to control the phenotype of mesenchymal stem cells (MSCs) for either cartilage or endochondral bone tissue engineering. To produce these gene-activated constructs, MSCs and nHA complexed with plasmid DNA (pDNA) encoding for transforming growth factor-beta 3 (pTGF-β3), bone morphogenetic protein 2 (pBMP2), or a combination of both (pTGF-β3–pBMP2) were encapsulated into alginate hydrogels. Initial analysis using reporter genes showed effective gene delivery and sustained overexpression of the transgenes were achieved. Confocal microscopy demonstrated that complexing the plasmid with nHA before hydrogel encapsulation led to transport of the plasmid into the nucleus of MSCs, which did not happen with naked pDNA. Gene delivery of TGF-β3 and BMP2 and subsequent cell-mediated expression of these therapeutic genes resulted in a significant increase in sulfated glycosaminoglycan and collagen production, particularly in the pTGF-β3–pBMP2 codelivery group in comparison to the delivery of either pTGF-β3 or pBMP2 in isolation. In addition, stronger staining for collagen type II deposition was observed in the pTGF-β3–pBMP2 codelivery group. In contrast, greater levels of calcium deposition were observed in the pTGF-β3- and pBMP2-only groups compared to codelivery, with a strong staining for collagen type X deposition, suggesting these constructs were supporting MSC hypertrophy and progression along an endochondral pathway. Together, these results suggest that the developed gene-activated alginate hydrogels were able to support transfection of encapsulated MSCs and directed their phenotype toward either a chondrogenic or an osteogenic phenotype depending on whether TGF-β3 and BMP2 were delivered in combination or isolation.

Controlled drug delivery systems, that include sequential and/or sustained drug delivery, have been utilized to enhance the therapeutic effects of many current drugs by effectively delivering drugs in a time-dependent and repeatable manner. In this study, with the aid of 3D printing technology, a novel drug delivery device was fabricated and tested to evaluate sequential delivery functionality. With an alginate shell and a poly(lactic-co-glycolic acid) (PLGA) core, the fabricated tubes displayed sequential release of distinct fluorescent dyes and showed no cytotoxicity when incubated with the human embryonic kidney (HEK293) cell line or bone marrow stromal stem cells (BMSC). The controlled differential release of drugs or proteins through such a delivery system has the potential to be used in a wide variety of biomedical applications from treating cancer to regenerative medicine.