Electrospun PU-PEG and PU-PC hybrid scaffolds for vascular tissue engineering

Produced via electrospinning, polyurethane (PU) scaffolds have always attracted the interest of medical applications due of their unique properties such as good adhesion, biocompatibility and excellent mechanical strength. However, the poor hydrophilicity and hemocompatibility of PU presented a problem during PU’s application in the manufacturing of biomedical materials. We hypothesized that the incorporation of polyethylene glycol (PEG) and phosphatidylcholine (PC) into electrospinning solution of PU could improve the cell affinity and hemocompatibility. This research focused on fabricating hybrid PU-PEG and PU-PC random/aligned scaffolds through electrospinning technique and comparing their properties as a potential biocompatible scaffold for vascular tissue engineering. PC was doped into a PU solution in order to prepare an electrospun scaffold through the electrospinning technology while crosslinked electrospun PUPEG hybrid scaffolds were fabricated by photoinduced polymerization. The contact angle dramatically decreased from 122.3±0.8° to 39.1±0.8° with doping of PC in electrospinning solution while it decreased from 122.3±0.8° to 41.6±0.8° with doping of PEG. Furthermore, the mechanical properties of PU scaffolds were altered significantly by the addition of PC. The hemolysis and cytocompatibility assays demonstrated that these composite scaffolds could potentially be used as a smalldiameter vascular graft.     

Formulation,Optimization and In Vivo Evaluation of Fucoidan-Based Cream with Anti-Inflammatory Properties

Fucoidan is a polysaccharide found in brown alga with glorious potential for pharmacological activities, among which its anti-inflammatory properties have gained meaningful attention. Due to several advantages of formulations for topical application, this study aimed to develop and optimize a fucoidan-based cream formulation and to investigate its anti-inflammatory potential after topical application in vivo. Fucoidan from Fucus vesiculosus L. was used. The cream base consisting of olive oil and Kolliphor RH40 was optimized followed by in vitro agar diffusion and drug release studies. The fucoidan-based cream with 13% Kolliphor P 407, 1% Transcutol P, and 5% PEG400 showed good spreadability, washability, and colloidal stability, and it did not irritate the skin. The kinetics of fucoidan release from the optimized cream exhibited the best fit to the Korsmeyer–Peppas and Higuchi models with R² > 0.99. Fucoidan release was controlled by drug diffusion and anomalous transport provided by the optimized cream base. The formulation was stable and provided high fucoidan release after storage for 1 year. Topical application of the fucoidan-based cream dose-dependently inhibited carrageenan-induced edema and ameliorated mechanical allodynia in rats. The efficacy of the fucoidan-based cream at a high dose was comparable with the efficacy of diclofenac gel. The fucoidan-based cream could be considered a promising anti-inflammatory formulation.     

Conductive 3D structure nanofibrous scaffolds for spinal cord regeneration

The complex nature of spinal cord injuries has provided much inspiration for the design of novel biomaterials and scaffolds which are capable of stimulating neural tissue repair strategies. Recently, conductive polymers have gained much attention for improving the nerve regeneration. In our previous study, a three-dimensional (3D) structure with reliable performance was achieved for electrospun scaffolds. The main purpose in the current study is formation of electrical excitable 3D scaffolds by appending polyaniline (PANI) to biocompatible polymers. In this paper, an attempt was made to develop conductive nanofibrous scaffolds, which can simultaneously present both electrical and topographical cues to cells. By using a proper 3D structure, two kinds of conductive scaffolds are compared with a non-conductive scaffold. The 3D nanofibrous core-sheath scaffolds, which are conductive, were prepared with nanorough sheath and aligned core. Two different sheath polymers, including poly(lactic-co-glycolic acid) PLGA and PLGA/PANI, with identical PCL/PANI cores were fabricated. Nanofibers of PCL and PLGA blends with PANI have fiber diameters of 234±60.8 nm and 770±166.6 nm, and conductivity of 3.17×10^-5 S/cm and 4.29×10^-5 S/cm, respectively. The cell proliferation evaluation of nerve cells on these two conductive scaffolds and previous non-conductive scaffolds (PLGA) indicate that the first conductive scaffold (PCL/ PANI-PLGA) could be more effective for nerve tissue regeneration. Locomotor scores of grafted animals by developed scaffolds showed significant performance of non-conductive 3D scaffolds. Moreover, the animal studies indicated the ability of two new types of conductive scaffolds as spinal cord regeneration candidates.     

Preparation and Characterization of Antioxidant Nanoparticles Composed of Chitosan and Fucoidan for Antibiotics Delivery

In this study, we developed novel chitosan/fucoidan nanoparticles (CS/F NPs) using a simple polyelectrolyte self-assembly method and evaluated their potential to be antioxidant carriers. As the CS/F weight ratio was 5/1, the CS/F NPs were spherical and exhibited diameters of approximately 230–250 nm, as demonstrated by TEM. These CS/F NPs maintained compactness and stability for 25 day in phosphate-buffered saline (pH 6.0–7.4). The CS/F NPs exhibited highly potent antioxidant effects by scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), reducing the concentration of intracellular reactive oxygen species (ROS) and superoxide anion (O₂⁻) in stimulated macrophages. The DPPH scavenging effect of CS/F NPs primarily derives from fucoidan. Furthermore, these CS/F NPs activated no host immune cells into inflammation-mediated cytotoxic conditions induced by IL-6 production and NO generation. The MTT cell viability assay revealed an absence of toxicity in A549 cells after exposure to the formulations containing 0.375 mg NPs/mL to 3 mg NPs/mL. Gentamicin (GM), an antibiotic, was used as a model drug for an in vitro releasing test. The CS/F NPs controlled the release of GM for up to 72 h, with 99% of release. The antioxidant CS/F NPs prepared in this study could thus be effective in delivering antibiotics to the lungs, particularly for airway inflammatory diseases.     

Chondrogenic differentiation of rat mesenchymal stem cells on silk fibroin/chondroitin sulfate/hyaluronic acid ternary scaffolds

Cartilage repair is a challenge in bone tissue reconstruction. In this study, silk fibroin (SF), chondroitin sulfate (CS) and hyaluronic acid (HA) were employed to fabricate scaffolds for tissue engineered cartilage by freeze drying technique. The secondary pores were formed in the main pores of SF/CS/HA scaffold which improved the pore connectivity and equilibrium swelling of the scaffold. Furthermore, rat bone marrow mesenchymal stem cells were seeded on the scaffolds to evaluate the cell adhesion and proliferation. Results of hematoxylin/eosin staining and cell counting kit-8 assay showed that the cells migration and differentiation of SF/CS/HA (80/15/5) scaffold were better than that of SF/CS/HA scaffolds with different ratios after 7 days culture. Moreover, immunohistochemistry and scanning electron microscope demonstrated that large amounts of collagen II and proteoglycans of the cells were expressed in the SF/CS/HA 3D scaffold, while the expression of collagen I was barely visible by immunohistochemistry. Abound of extracellular matrix was formed to morphologically round and distributed uniformly throughout the scaffolds. The 3D ternary scaffold could promote the cells chondrogenic differentiation without using any inductive agent and offer potential for cartilage tissue regeneration.     

Intestinal Absorption of Fucoidan Extracted from the Brown Seaweed,Cladosiphon okamuranus

The aim of this study was to examine the absorption of fucoidan through the intestinal tract. Fucoidan (0.1, 0.5, 1.0, 1.5 and 2.0 mg/mL) was added to Transwell inserts containing Caco-2 cells. The transport of fucoidan across Caco-2 cells increased in a dose-dependent manner up to 1.0 mg/mL. It reached a maximum after 1 h and then rapidly decreased. In another experiment, rats were fed standard chow containing 2% fucoidan for one or two weeks. Immunohistochemical staining revealed that fucoidan accumulated in jejunal epithelial cells, mononuclear cells in the jejunal lamina propria and sinusoidal non-parenchymal cells in the liver. Since we previously speculated that nitrosamine may enhance the intestinal absorption of fucoidan, its absorption was estimated in rats administered N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water. Rats were fed 0.2% fucoidan chow (BBN + 0.2% fucoidan rats), 2% fucoidan chow (BBN + 2% fucoidan rats) and standard chow for eight weeks. The uptake of fucoidan through the intestinal tract seemed to be low, but was measurable by our ELISA method. Fucoidan-positive cells were abundant in the small intestinal mucosa of BBN + 2% fucoidan rats. Most fucoidan-positive cells also stained positive for ED1, suggesting that fucoidan was incorporated into intestinal macrophages. The uptake of fucoidan by Kupffer cells was observed in the livers of BBN + 2% fucoidan rats. In conclusion, the absorption of fucoidan through the small intestine was demonstrated both in vivo and in vitro.     

Fucoidan from Fucus vesiculosus Protects against Alcohol-Induced Liver Damage by Modulating Inflammatory Mediators in Mice and HepG2 Cells

Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg) for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-β1), a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-β1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions.     

The Anticancer Effect of Fucoidan in PC-3 Prostate Cancer Cells

Fucoidan, a sulfated polysaccharide, has a variety of biological activities, such as anti-cancer, anti-angiogenic and anti-inflammatory. However, the mechanisms of action of fucoidan as an anti-cancer agent have not been fully elucidated. The present study examined the anti-cancer effect of fucoidan obtained from Undaria pinnatifida in PC-3 cells, human prostate cancer cells. Fucoidan induced the apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The induction of apoptosis was accompanied by the activation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt. In addition, fucoidan also induced the up-regulation of p21^Cip1/Waf and down-regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/β-catenin pathway, fucoidan activated GSK-3β that resulted in the decrease of β-catenin level, followed by the decrease of c-myc and cyclin D1 expressions, target genes of β-catenin in PC-3 cells. These results suggested that fucoidan treatment could induce intrinsic and extrinsic apoptosis pathways via the activation of ERK1/2 MAPK, the inactivation of p38 MAPK and PI3K/Akt signaling pathway, and the down-regulation of Wnt/β-catenin signaling pathway in PC-3 prostate cancer cells. These data support that fucoidan might have potential for the treatment of prostate cancer.     

Fucoidan Independently Enhances Activity in Human Immune Cells and Has a Cytostatic Effect on Prostate Cancer Cells in the Presence of Nivolumab

Fucoidan compounds may increase immune activity and are known to have cancer inhibitory effects in vitro and in vivo. In this study, we aimed to investigate the effect of fucoidan compounds on ex vivo human peripheral blood mononuclear cells (PBMCs), and to determine their cancer cell killing activity both solely, and in combination with an immune-checkpoint inhibitor drug, Nivolumab. Proliferation of PBMCs and interferon gamma (IFNγ) release were assessed in the presence of fucoidan compounds extracted from Fucus vesiculosus, Undaria pinnatifida and Macrocystis pyrifera. Total cell numbers and cell killing activity were assessed using a hormone resistant prostate cancer cell line, PC3. All fucoidan compounds activated PBMCs, and increased the effects of Nivolumab. All fucoidan compounds had significant direct cytostatic effects on PC3 cells, reducing cancer cell numbers, and PBMCs exhibited cell killing activity as measured by apoptosis. However, there was no fucoidan mediated increase in the cell killing activity. In conclusion, fucoidan compounds promoted proliferation and activity of PBMCs and added to the effects of Nivolumab. Fucoidan compounds all had a direct cytostatic effect on PC3 cells, as shown through their proliferation reduction, while their killing was not increased.     

Fabrication of silver nanoparticle/polyvinyl alcohol/polycaprolactone hybrid nanofibers nonwovens by two-nozzle electrospinning for wound dressing

In this study, two biodegradable polymers, polycaprolactone (PCL) and polyvinyl alcohol (PVA) were used to fabricate nanofiber nonwovens (NFNs). Also, the silver nanoparticles (AgNPs) successfully reduced by using tea polyphenols (TP) and incorporated in the NFNs via electrospinning. The morphologies of the NFNs and AgNPs were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), respectively. The PCL nanofibers and PVA nanofibers interweaved each other, and AgNPs with average diameter 1.53±0.15 nm were embedded in the PVA nanofibers. The properties of electrospun NFNs were characterized by pore property, swelling/weight loss, water contact angle, mechanical property, and antibacterial activity. The nanofibers cross-linked to each other forming the 3Dnetwork porous structure with diameter about 1-1.5 μm. Although the hydrophobic PCL was added in the hybrid NFNs, the NFNs still showed hydrophilic propriety, high swelling degree (i.e. swelling degree is 330 % for 48 h), and low weight loss (i.e. weight loss is 22.4 % for 48 h). Also, the hybrid PCL/PVA/AgNPs NFNs exhibited a suitable mechanical property for wound dressings (i.e. tensile strength is 4.27 MPa, and breaking elongation is 88 %). Moreover, the hybrid NFNs effectively inhibited growth of Escherichia coli and Staphylococcus aureus. In summary, this PCL/PVA/AgNPs NFNs may provide a promising candidate for accelerating wound healing.     

Fabrication of Biocompatible PLGA/PCL/PANI Nanofibrous Scaffolds with Electrical Excitability

Application of electrospun nanofibrous scaffolds has received immense attention in tissue engineering. Fabrication of scaffolds with appropriate electrical properties plays a key role in neural tissue engineering. Since fibers orientation in the scaffolds affects the growth and proliferation of the cells, this study aimed to prepare aligned electrospun conductive nanofibers by mixing 1 %, 10 % and 18 % (w/v) doped polyaniline (PANI) with polycaprolactone (PCL)/poly lactic-coglycolic acid (PLGA) (25/75) solution through the electrospinning process. The fibers diameter, hydrophilicity and conductivity were measured. In addition, the shape and proliferation of the nerve cells seeded on fibers were evaluated by MTT cytotoxicity assay and scanning electron microscopy. The results revealed that the conductive nanofibrous scaffolds were appropriate substrates for the attachment and proliferation of nerve cells. The electrical stimulation enhanced neurite outgrowth compared to those PLGA/PCL/PANI scaffolds that were not subjected to electrical stimulation. As polyaniline ratio increases, electric stimulation through nanofibrous PLGA/PCL/PANI scaffolds results in cell proliferation enhancement. However, a raise more than 10 % in polyaniline will result in cell toxicity. It was concluded that conductive scaffolds with appropriate ratio of PANI along with electrical stimulation have potential applications in treatment of spinal cord injuries.     

Silk fibroin/hyaluronic acid porous scaffold for dermal wound healing

The use of silk protein as a biomaterial has been studied for decades. In this study, silk fibroin (SF)/hyaluronic acid (HA) blend scaffolds were prepared by freeze-drying technique. The structure and properties of the blend scaffolds were examined and analyzed. The results demonstrated that the secondary structures of the SF/HA scaffolds were mainly amorphous and β-sheet structures. The pore radius and porosity of the scaffolds decreased with a decrease in the freezing temperature decrease and an increase in the HA ratio. The pore radius and porosity were regulated from 32.22 μm to 290.76 μm and from 74.1 % to 91.15 %, respectively. In vitro, the SF/HA scaffolds could support the fibroblast cell adhesion and proliferation and showed good cytocompatibility. In vivo, the SF/HA scaffolds were implanted into the dorsum of Sprague Dawley rats to evaluate their bioactivity for dermal tissue reconstruction. The vascular-like structures appeared more rapidly in SF/HA scaffolds than that in the PVA group, and a new dermal layer was formed, as determined by histological analysis. The SF/HA porous scaffolds have promise as a dermal substitute.     

Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma

Metastasis, the greatest clinical challenge associated with cancer, is closely connected to multiple biological processes, including invasion and adhesion. The hypoxic environment in tumors is an important factor that causes tumor metastasis by activating HIF-1α. Fucoidan, extracted from brown algae, is a sulfated polysaccharide and, as a novel marine biological material, has been used to treat various disorders in China, Korea, Japan and other countries. In the present study, we demonstrated that fucoidan derived from Undaria pinnatifida sporophylls significantly inhibits the hypoxia-induced expression, nuclear translocation and activity of HIF-1α, the synthesis and secretion of VEGF-C and HGF, cell invasion and lymphatic metastasis in a mouse hepatocarcinoma Hca-F cell line. Fucoidan also suppressed lymphangiogenesis in vitro and in vivo. In addition, accompanied by a reduction in the HIF-1α nuclear translocation and activity, fucoidan significantly reduced the levels of p-PI3K, p-Akt, p-mTOR, p-ERK, NF-κB, MMP-2 and MMP-9, but increased TIMP-1 levels. These results indicate strongly that the anti-metastasis and anti-lymphangiogenesis activities of fucoidan are mediated by suppressing HIF-1α/VEGF-C, which attenuates the PI3K/Akt/mTOR signaling pathways.     

Reinforcement of wet milled jute nano/micro particles in polyvinyl alcohol films

Textile industry generate significant amount of waste fibres in form of short lengths during mechanical processing. However these short fibres possess excellent properties suitable for many other applications. The objective of this work was to use them for the preparation of nanoparticles/nanofibres as fillers in biodegradable composite applications such as food packaging, agriculture mulch films, automotive plastics, etc. The present paper concerns with jute fibres as a source of nanocellulose for reinforcement of PVA mulch films. Jute fibres were first refined to micro/nanoscale particles in form of nanofibrillar cellulose (NFC) by high energy planetary ball milling process in dry and wet condition. Wet milling was observed more efficient than dry milling in terms of unimodality of size distribution with reduction in size below 500 nm after milling for 3 hours. Later the obtained particles were used as fillers in Poly vinyl alcohol (PVA) films and their reinforcement evaluated based on thermal properties. It was observed that glass transition temperature (T_g) of PVA films improved from 84.36 °C to 95.22 °C after addition of 5 % jute particles without affecting % crystallinity and melting temperature (T _m) of PVA. Dynamic mechanical analysis of composite films with 5 % jute particles showed higher value of 14×10⁸ Pa for storage modulus in comparison to 9×10⁸ Pa of neat composite film. The percolation effect was observed more above glass transition temperature which consequently resulted in improved transfer of stiffness from jute particles to PVA matrix above 50 °C. The percolation phenomena also explained the improvement in thermal stability by 10 °C for every increased loading of jute particles due to formation of hydrogen bonds with PVA matrix.     

Fucoidan from marine brown algae inhibits lipid accumulation

In this study, we elucidated the inhibitory effect of fucoidan from marine brown algae on the lipid accumulation in differentiated 3T3-L1 adipocytes and its mechanism. The treatment of fucoidan in a dose-dependent manner was examined on lipid inhibition in 3T3-L1 cells by using Oil Red O staining. Fucoidan showed high lipid inhibition activity at 200 μg/mL concentration (P < 0.001). Lipolytic activity in adipocytes is highly dependent on hormone sensitive lipase (HSL), which is one of the most important targets of lipolytic regulation. Here, we examined the biological response of fucoidan on the protein level of lipolysis pathway. The expressed protein levels of total hormone sensitive lipase (HSL) and its activated form, phosphorylated-HSL were significantly increased at concentration of 200 μg/mL fucoidan. Furthermore, insulin-induced 2-deoxy-D-[3H] glucose uptake was decreased up to 51% in fucoidan-treated cells as compared to control. Since increase of HSL and p-HSL expression and decrease of glucose uptake into adipocytes are known to lead to stimulation of lipolysis, our results suggest that fucoidan reduces lipid accumulation by stimulating lipolysis. Therefore, these results suggest that fucoidan can be useful for the prevention or treatment of obesity due to its stimulatory lipolysis.     

A 3D-Printed Polycaprolactone/Marine Collagen Scaffold Reinforced with Carbonated Hydroxyapatite from Fish Bones for Bone Regeneration

In bone tissue regeneration, extracellular matrix (ECM) and bioceramics are important factors, because of their osteogenic potential and cell–matrix interactions. Surface modifications with hydrophilic material including proteins show significant potential in tissue engineering applications, because scaffolds are generally fabricated using synthetic polymers and bioceramics. In the present study, carbonated hydroxyapatite (CHA) and marine atelocollagen (MC) were extracted from the bones and skins, respectively, of Paralichthys olivaceus. The extracted CHA was characterized using Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analysis, while MC was characterized using FTIR spectroscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The scaffolds consisting of polycaprolactone (PCL), and different compositions of CHA (2.5%, 5%, and 10%) were fabricated using a three-axis plotting system and coated with 2% MC. Then, the MC3T3-E1 cells were seeded on the scaffolds to evaluate the osteogenic differentiation in vitro, and in vivo calvarial implantation of the scaffolds was performed to study bone tissue regeneration. The results of mineralization confirmed that the MC/PCL, 2.5% CHA/MC/PCL, 5% CHA/MC/PCL, and 10% CHA/MC/PCL scaffolds increased osteogenic differentiation by 302%, 858%, 970%, and 1044%, respectively, compared with pure PCL scaffolds. Consequently, these results suggest that CHA and MC obtained from byproducts of P. olivaceus are superior alternatives for land animal-derived substances.     

Polyanizidine and Polycaprolactone Nanofibers for Designing the Conductive Scaffolds

The main objective of this work was chemically bioactivation of the conducting polyanizidine (PANIZ) by incorporating a polyester such as polycaprolactone (PCL). Modified PANIZ nanocomposites were synthesized through ring opening and chemical oxidation polymerizations. A four-point probe was applied to measure the conductivity of newly synthesized star-like block copolymer (S-PCL-PANIZ) nanocomposite, which was about 0.44 S cm^-1. Conductive biodegradable nanofibers were prepared by electrospinning with 25 and 75 % (wt/wt) S-PCL-PANIZ to PCL. The contact angle of each prepared nanofiber was 87±3°, supporting their usefulness for cell culture. The cultured mouse osteoblast MG63 cells demonstrated normal morphology and significantly higher adhesion and spreading on the nanofiber. The bioactivated PANIZ based nanocomposite may be fruitful in tissue engineering to fabricate conducting biodegradable scaffolds with improved cell adhesion properties for various cell cultures.     

Injectable Thermosensitive Chitosan-Collagen Hydrogel as A Delivery System for Marine Polysaccharide Fucoidan

Fucoidans, sulfated polysaccharides from brown algae, possess multiple bioactivities in regard to osteogenesis, angiogenesis, and inflammation, all representing key molecular processes for successful bone regeneration. To utilize fucoidans in regenerative medicine, a delivery system is needed which temporarily immobilizes the polysaccharide at the injured site. Hydrogels have become increasingly interesting biomaterials for the support of bone regeneration. Their structural resemblance with the extracellular matrix, their flexible shape, and capacity to deliver bioactive compounds or stem cells into the affected tissue make them promising materials for the support of healing processes. Especially injectable hydrogels stand out due to their minimal invasive application. In the current study, we developed an injectable thermosensitive hydrogel for the delivery of fucoidan based on chitosan, collagen, and β-glycerophosphate (β-GP). Physicochemical parameters such as gelation time, gelation temperature, swelling capacity, pH, and internal microstructure were studied. Further, human bone-derived mesenchymal stem cells (MSC) and human outgrowth endothelial cells (OEC) were cultured on top (2D) or inside the hydrogels (3D) to assess the biocompatibility. We found that the sol-gel transition occurred after approximately 1 min at 37 °C. Fucoidan integration into the hydrogel had no or only a minor impact on the mentioned physicochemical parameters compared to hydrogels which did not contain fucoidan. Release assays showed that 60% and 80% of the fucoidan was released from the hydrogel after two and six days, respectively. The hydrogel was biocompatible with MSC and OEC with a limitation for OEC encapsulation. This study demonstrates the potential of thermosensitive chitosan-collagen hydrogels as a delivery system for fucoidan and MSC for the use in regenerative medicine.     

Structural Characterization and In Vivo Anti-Inflammatory Activity of Fucoidan from Cystoseira crinita (Desf.) Borry

The aim of this study was to evaluate the effects of fucoidan isolated from C. crinita on histamine-induced paw inflammation in rats, and on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 in rats during systemic inflammation response. The levels of TNF-α in a model of acute peritonitis in rats were also investigated. The isolated crude fucoidan was identified as a sulfated xylogalactofucan with high, medium, and low molecular weight fractions and a content of fucose of 39.74%, xylose of 20.75%, and galactose of 15.51%. Fucoidan from C. crinita showed better anti-inflammatory effects in the rat paw edema model, and this effect was present during all stages of the experiment. When compared to controls, a commercial fucoidan from F. vesiculosus, the results also displayed anti-inflammatory activity on the 60th, 90th, and 120th minute of the experiment. A significant decrease in serum levels of IL-1β in rats treated with both doses of C. crinita fucoidan was observed in comparison to controls, whereas TNF-α concentrations were reduced only in the group treated with fucoidan from C. crinita at the dose of 25 mg/kg bw. In the model of carrageenan-induced peritonitis, we observed a tendency of decrease in the levels of the pro-inflammatory cytokine TNF-α in peritoneal fluid after a single dose of C. crinita fucoidan, but this did not reach the statistical significance margin. Single doses of C. crinita fucoidan did not alter serum levels of the anti-inflammatory cytokine IL-10 in animals with lipopolysaccharide-induced systemic inflammation.