A Gellan Gum, Polyethylene Glycol, Hydroxyapatite Composite Scaffold with the Addition of Ginseng Derived Compound K with Possible Applications in Bone Regeneration.

Engineered bone scaffolds should mimic the natural material to promote cell adhesion and regeneration. For this reason, natural biopolymers are becoming a gold standard in scaffold production. In this study, we proposed a hybrid scaffold produced using gellan gum, hydroxyapatite, and Poly (ethylene glycol) within the addition of the ginseng compound K (CK) as a candidate for bone regeneration. The fabricated scaffold was physiochemically characterized. The morphology studied by scanning electron microscopy (SEM) and image analysis revealed a pore distribution suitable for cells growth. The addition of CK further improved the biological activity of the hybrid scaffold as demonstrated by the MTT assay. The addition of CK influenced the scaffold morphology, decreasing the mean pore diameter. These findings can potentially help the development of a new generation of hybrid scaffolds to best mimic the natural tissue.

Cartilage regeneration using transforming growth factor-beta 3-loaded injectable crosslinked hyaluronic acid hydrogel.

Cartilage defects can be difficult to heal, potentially leading to complications such as osteoarthritis. Recently, a tissue engineering approach that uses scaffolds and growth factors has been proposed to regenerate new cartilage tissues. Herein, we investigated the application of hyaluronic acid (HA) gel loaded with transforming growth factor-beta 3 (TGF-ß3) for enhanced cartilage regeneration. We assessed the clinical conditions required to efficiently enhance the ability of the modified HA gel to repair defective cartilage. Based on our findings, the prepared HA gel exhibited good physicochemical and mechanical properties and was non-toxic and non-inflammatory. Moreover, HA gel-loaded TGF-ß3 (HAT) had improved biocompatibility and promoted the synthesis of cartilage-specific matrix and collagen, further improving its ability to repair defects. The application of HAT resulted in an initial burst release of HA, which degraded slowly in vivo. Finally, HAT combined with microfracture-inducing bone marrow stem cells could significantly improve the cartilage microenvironment and regeneration of cartilage defects. Our results indicate that HA is a suitable material for developing growth factor carriers, whereas HAT is a promising candidate for cartilage regeneration. Furthermore, this differentiated strategy provides a rapid and effective clinical approach for next-generation cartilage regeneration.

Evaluation of Silk Fibroin/Gellan Gum Hydrogels with Controlled Molecular Weight through Silk Fibroin Hydrolysis for Tissue Engineering Application.

Hydrogel is a versatile material that can be manipulated to achieve the desired physicochemical properties, such as stiffness, pore size, and viscoelasticity. Traditionally, these properties have been controlled through parameters such as concentration and pH adjustments. In this study, we focused on exploring the potential of hydrolyzed silk fibroin (HSF) as a molecular weight-modulating agent to control the physicochemical properties of double-composite hydrogels. We developed a synergistic dual-crosslinked hydrogel by combining ionically crosslinked silk fibroin with gellan gum (GG). The hydrolysis of silk fibroin not only enhanced its hydrophilicity but also enabled adjustments in its mechanical properties, including the pore size, initial modulus elasticity, and relaxation time. Moreover, biocompatibility assessments based on cell viability tests confirmed the potential of these hydrogels as biocompatible materials. By highlighting the significance of developing an HSF/GG dual-crosslinked hydrogel, this study contributes to the advancement of novel double-composite hydrogels with remarkable biocompatibility. Overall, our findings demonstrate the capability of controlling the mechanical properties of hydrogels through molecular weight modulation via hydrolysis and highlight the development of a biocompatible HSF/GG dual-crosslinked hydrogel with potential biomedical applications.

Modified gellan gum-based hydrogel with enhanced mechanical properties for application as a cell carrier for cornea endothelial cells.

Recently, the number of people suffering from visual loss due to eye diseases is increasing rapidly around the world. However, due to the severe donor shortage and the immune response, corneal replacement is needed. Gellan gum (GG) is biocompatible and widely used for cell delivery or drug delivery, but its strength is not suitable for the corneal substitute. In this study, a GM hydrogel was prepared by blending methacrylated gellan gum with GG (GM) to give suitable mechanical properties to the corneal tissue. In addition, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), a crosslinking initiator, was added to the GM hydrogel. After the photo-crosslinking treatment, it was named GM/LAP hydrogel. GM and GM/LAP hydrogels were analyzed for physicochemical properties, mechanical characterization, and transparency tests to confirm their applicability as carriers for corneal endothelial cells (CEnCs). Also, in vitro studies were performed with cell viability tests, cell proliferation tests, cell morphology, cell-matrix remodeling analysis, and gene expression evaluation. The compressive strength of the GM/LAP hydrogel was improved compared to the GM hydrogel. The GM/LAP hydrogel showed excellent cell viability, proliferation, and cornea-specific gene expression than the GM hydrogel. Crosslinking-improved GM/LAP hydrogel can be applied as a promising cell carrier in corneal tissue engineering.

Development of Gelatin-Based Shape-Memory Polymer Scaffolds with Fast Responsive Performance and Enhanced Mechanical Properties for Tissue Engineering Applications.

Shape-memory polymers (SMPs) can be defined as a reversibly changing form through deformation and recovery by external stimuli. However, there remain application limitations of SMPs, such as complicated preparation processes and slow shape recovery. Here, we designed gelatin-based shape-memory scaffolds by a facile dipping method in tannic acid solution. The shape-memory effect of scaffolds was attributed to the hydrogen bond between gelatin and tannic acid, which acts as the net point. Moreover, gelatin (Gel)/oxidized gellan gum (OGG)/calcium chloride (Ca) was intended to induce faster and more stable shape-memory behavior through the introduction of a Schiff base reaction. The chemical, morphological, physicochemical, and mechanical properties of the fabricated scaffolds were evaluated, and those results showed that the Gel/OGG/Ca had improved mechanical properties and structural stability compared with other scaffold groups. Additionally, Gel/OGG/Ca exhibited excellent shape-recovery behavior of 95.8% at 37 °C. As a consequence, the proposed scaffolds can be fixed to the temporary shape at 25 °C in just 1 s and recovered to the original shape at 37 °C within 30 s, implying a great potential for minimally invasive implantation.

Accelerating bone regeneration using poly(lactic-co-glycolic acid)/hydroxyapatite scaffolds containing duck feet-derived collagen.

Collagen, with low antigenicity and excellent cell adhesion, is a biomaterial mainly used for regenerating bone, cartilage, and skin, owing to its biocompatibility and biodegradability. Results from a previous study confirmed that a scaffold mixed with duck feet-derived collagen (DC) and Poly(lactic-co-glycolic acid) (PLGA) reduced inflammatory reaction and increased bone regeneration. To develop an optimal bone substitute we included hydroxyapatite (HAp), a key osteoconductive material, in a DC and PLGA mixture. We fabricated 0, 10, 20, 40, 60, and 80 wt% DC/PLGA/HAp scaffolds and studied their potential for bone tissue engineering. Characteristic analysis of the scaffold and seeding of rabbit bone marrow mesenchymal stem cells (rBMSCs) on the scaffold were conducted to investigate cell proliferation, osteogenic differentiation, and bone formation. We confirmed that increasing DC concentration not only improved the compressive strength of the DC/PLGA/HAp scaffold but also cell proliferation and osteogenic differentiation. It was found through comparison with previous studies that including HAp in the scaffold also promotes osteogenic differentiation. Our study thus shows through in vivo results that the 80 wt% DC/PLGA/HAp scaffold promotes bone mineralization and collagen deposition while reducing the inflammatory response. Hence, 80 wt% DC/PLGA/HAp has excellent potential as a biomaterial for bone regeneration applications.

Injectable Hydrogel Based on Gellan Gum/Silk Sericin for Application as a Retinal Pigment Epithelium Cell Carrier.

The damage to retinal pigment epithelium (RPE) cells can lead to vision loss and permanent blindness. Therefore, an effective therapeutic strategy has emerged to replace damaged cells through RPE cell delivery. In this study, we fabricated injectable gellan gum (GG)/silk sericin (SS) hydrogels as a cell carrier by blending GG and SS. To determine the appropriate concentration of SS for human RPE ARPE-19, 0, 0.05, 0.1, and 0.5% (w/v) of SS solution were blended in 1% (w/v) GG solution (GG/SS 0%, GG/SS 0.05%, GG/SS 0.1%, and GG/SS 0.5%, respectively). The physical and chemical properties were measured through Fourier-transform infrared spectroscopy, scanning electron microscopy, mass swelling, and weight loss. Also, viscosity, injection force, and compressive tests were used to evaluate mechanical characteristics. Cell proliferation and differentiation of ARPE-19 were evaluated using quantitative dsDNA analysis and real-time polymerase chain reaction, respectively. The addition of SS gave GG/SS hydrogels a compressive strength similar to that of natural RPE tissue, which may well support the growth of RPE and enhance cell proliferation and differentiation. In particular, the GG/SS 0.5% hydrogel showed the most similar compressive strength (about 10 kPa) and exhibited the highest gene expression related to ARPE-19 cell proliferation. These results indicate that GG/SS 0.5% hydrogels can be a promising biomaterial for cell delivery in retina tissue engineering.

Fast stress relaxing gellan gum that enhances the microenvironment and secreting function of bone mesenchymal stem cells.

This study shows tunable stress relaxing gellan gum (GG) hydrogel for enhanced cell growth and regenerative medicine. The molecular weight and physical crosslinking density of GG were tuned and characterized with physicochemical analysis and mechanical tests. The result showed that a decrease in the molecular weight of the GG correlated with a decline in the mechanical properties but faster stress relaxing character. We also discovered that human-derived bone marrow stem cells (hBMSC) showed active viability, proliferation, and remodeling in the fast stress relaxing GG hydrogel. In particular, hBMSC showed an enhanced release profile of growth factors and exosomes (Exo) in the fast stress relaxing GG hydrogel. The secretome obtained from hBMSC embedded in hydrogel exhibited similar cytotoxicity and wound healing properties to that of secretome extracted from hBMSC cultured in a tissue culture plate (TCP) a standard culture condition. Thus, this work demonstrates the potential of fast stress relaxing GG hydrogels for medical application.

Evaluation of Human Osteoblasts on NIPS Micro-Patterned PCL Carriers Containing Nanohydroxyapatite and Reduced Graphene Oxide Using PSµM.

The content and surface topology of tissue engineering scaffolds are two important parameters in regulating the cell behavior. In this study, a phase separation micromolding (PSµM) method was implemented to develop micro-groove-imprinted poly(ε-caprolactone) (PCL)-nano hydroxyapatite (nHAp)-reduced graphene oxide (rGO) ternary blend constructs. Physical and chemical characterizations of cell-devoid constructs were performed by FTIR, XRD, TGA, DSC, porosity, swelling, wettability analysis, tensile and compression mechanical tests. The in vitro biological performance of human osteoblasts cultured on micro-patterned blend constructs was evaluated by MTT and alamarBlue viability assays. The findings revealed that nHAp and rGO significantly promote cell viability and proliferation, while the micro-pattern determines the direction of cell migration. Alkaline phosphatase and Ca2+ analyses were carried out to determine the osteogenic properties of cell-laden constructs. This study describes a simple method to generate topologically modified ternary blend PCL/nHAp/rGO constructs using the PSµM method, which contributes to cell proliferation and migration, which is particularly important in regenerative medicine.

Fabrication and Evaluation of Gellan Gum/Hyaluronic Acid Hydrogel for Retinal Tissue Engineering Biomaterial and the Influence of Substrate Stress Relaxation on Retinal Pigment Epithelial Cells.

Cell therapies for age-related macular degeneration (AMD) treatment have been developed by integrating hydrogel-based biomaterials. Until now, cell activity has been observed only in terms of the modulus of the hydrogel. In addition, cell behavior has only been observed in the 2D environment of the hydrogel and the 3D matrix. As time-dependent stress relaxation is considered a significant mechanical cue for the control of cellular activities, it is important to optimize hydrogels for retinal tissue engineering (TE) by applying this viewpoint. Herein, a gellan Gum (GG)/Hyaluronic acid (HA) hydrogel was fabricated using a facile physical crosslinking method. The physicochemical and mechanical properties were controlled by forming a different composition of GG and HA. The characterization was performed by conducting a mass swelling study, a sol fraction study, a weight loss test, a viscosity test, an injection force study, a compression test, and a stress relaxation analysis. The biological activity of the cells encapsulated in 3D constructs was evaluated by conducting a morphological study, a proliferation test, a live/dead analysis, histology, immunofluorescence staining, and a gene expression study to determine the most appropriate material for retinal TE biomaterial. Hydrogels with moderate amounts of HA showed improved physicochemical and mechanical properties suitable for injection into the retina. Moreover, the time-dependent stress relaxation property of the GG/HA hydrogel was enhanced when the appropriate amount of HA was loaded. In addition, the cellular compatibility of the GG/HA hydrogel in in vitro experiments was significantly improved in the fast-relaxing hydrogel. Overall, these results demonstrate the remarkable potential of GG/HA hydrogel as an injectable hydrogel for retinal TE and the importance of the stress relaxation property when designing retinal TE hydrogels. Therefore, we believe that GG/HA hydrogel is a prospective candidate for retinal TE biomaterial.

Macro- and microporous polycaprolactone/duck's feet collagen scaffold fabricated by combining facile phase separation and particulate leaching techniques to enhance osteogenesis for bone tissue engineering.

Herein, a facile macro- and microporous polycaprolactone/duck's feet collagen scaffold (PCL/DC) was fabricated and characterized to confirm its applicability in bone tissue engineering. A biomimetic scaffold for bone tissue engineering and regeneration for bone defects is an important element. PCL is a widely applied biomaterial for bone tissue engineering due to its biocompatibility and biodegradability. However, the high hydrophobicity and low cell attachment site properties of PCL lead to an insufficient microenvironment in designing a scaffold. Collagen is a nature-derived biomaterial that is widely used in tissue engineering and has excellent biocompatibility, mechanical properties, and cell attachment moieties. Among the resources from which collagen can be obtained, DC contains a high amount of collagen type I (COL1), is biocompatible, and is cost-effective. In this study, the scaffolds were fabricated by blending DC with PCL in various ratios and applied non-solvent-induced phase separation (NIPS) and thermal-induced phase separation (TIPS) (N-TIPS), solvent casting and particulate leaching (SCPL), and gas foaming method to fabricate macro- and microporous structure. The characterization of the fabricated scaffolds was carried out by morphological analysis, bioactivity test, physicochemical analysis, and mechanical test. In vitro study was carried out by viability test, morphology observation, and gene expression. The results showed that the incorporation of DC enhances the physicochemical and mechanical properties of the scaffolds. Also, a large amount of bone mimetic apatite was formed according to the DC content in the bioactivity test. The in vitro study showed that the PCL/DC scaffold is biocompatible and the existence of apatite and DC formed a favorable microenvironment for cell proliferation and differentiation. Overall, the novel porous PCL/DC scaffold can be a promising biomaterial model for bone tissue engineering and regeneration.

Biomimetic sponge using duck's feet derived collagen and hydroxyapatite to promote bone regeneration.

Collagen, a natural biomaterial derived from animal tissues, has attracted the attention of biomedical material researchers because of its excellent cell affinity and low rejection in vivo. In this study, collagen was extracted using livestock by-product flippers, and an experiment was performed to assess its application as a scaffold for bone tissue implantation. For this purpose, we fabricated 2%, and 3% duck's feet derived collagen (DC) sponges. We then compared them to hydroxyapatite (HAp)-coated DC sponges, and measured the porosity and pore size using scanning electron microscopy (SEM) to analyze the physical properties and morphology of DC and DC/HAp sponges. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were carried out to measure the proliferation of bone marrow stem cells (BMSCs) in DC and DC/HAp sponges. An alkaline phosphatase activity assay confirmed the osteogenic differentiation ability of BMSCs. Polymerase chain reaction (PCR) was performed to confirm the BMSC-specific genetic marker. The osteogenic potential was confirmed by the bone formation in an in vivo environment on the scaffold by histological and immunohistochemical analysis. Overall, this study shows that DC/HAp sponges have biocompatibility and good physical properties. Additionally, DC/HAp sponges show potential use as bone graft materials for tissue engineering applications.

Preparation of Foam Dressings Based on Gelatin, Hyaluronic Acid, and Carboxymethyl Chitosan Containing Fibroblast Growth Factor-7 for Dermal Regeneration.

Wound recovery close to the function of the native skin is the goal of wound healing. In this study, we prepared foam dressings (FDs; 2-GHC-FD-1-9, 5-GHC-FD-1-9, and 10-GHC-FD-1-9) composed of various concentrations of gelatin, hyaluronic acid, and carboxymethyl chitosan, which are chemically interconnected through amide bond formation, for evaluating wound healing. Tensile and cell proliferation tests showed that 2-GHC-FD-1-9 are suitable for wound dressing. For further evaluation, three types of FDs, 2-GHC-FD-1, 2-GHC-FD-4, and 2-GHC-FD-8 were chosen. The results of animal intradermal reactivity, water vapor transmission rate, and absorption rate of the three FDs indicated that 2-GHC-FD-8 is the most appropriate scaffold for wound healing. For wound healing acceleration, various concentrations of fibroblast growth factor-7 (FGF-7) was soaked in 2-GHC-FD-8 (2-GHC-FD-8/F1-6) and evaluated by using scanning electron microscopy, cell proliferation, release behavior, and in vivo animal tests. The FDs showed interconnected porous structures, increased cell proliferation until 8.0 × 10-11 M, controlled release with initial burst within 1 h, and sustained release for 48 h. The results of the animal test showed an appropriate concentration of FGF-7 for wound healing. In addition, 2-GHC-FD-8 is a suitable scaffold for wound healing. Therefore, we suggest that 2-GHC-FD-8/F3 is a useful wound dressing for accelerating wound healing.

Development and Evaluation of Gellan Gum/Silk Fibroin/Chondroitin Sulfate Ternary Injectable Hydrogel for Cartilage Tissue Engineering.

Hydrogel is in the spotlight as a useful biomaterial in the field of drug delivery and tissue engineering due to its similar biological properties to a native extracellular matrix (ECM). Herein, we proposed a ternary hydrogel of gellan gum (GG), silk fibroin (SF), and chondroitin sulfate (CS) as a biomaterial for cartilage tissue engineering. The hydrogels were fabricated with a facile combination of the physical and chemical crosslinking method. The purpose of this study was to find the proper content of SF and GG for the ternary matrix and confirm the applicability of the hydrogel in vitro and in vivo. The chemical and mechanical properties were measured to confirm the suitability of the hydrogel for cartilage tissue engineering. The biocompatibility of the hydrogels was investigated by analyzing the cell morphology, adhesion, proliferation, migration, and growth of articular chondrocytes-laden hydrogels. The results showed that the higher proportion of GG enhanced the mechanical properties of the hydrogel but the groups with over 0.75% of GG exhibited gelling temperatures over 40 °C, which was a harsh condition for cell encapsulation. The 0.3% GG/3.7% SF/CS and 0.5% GG/3.5% SF/CS hydrogels were chosen for the in vitro study. The cells that were encapsulated in the hydrogels did not show any abnormalities and exhibited low cytotoxicity. The biochemical properties and gene expression of the encapsulated cells exhibited positive cell growth and expression of cartilage-specific ECM and genes in the 0.5% GG/3.5% SF/CS hydrogel. Overall, the study of the GG/SF/CS ternary hydrogel with an appropriate content showed that the combination of GG, SF, and CS can synergistically promote articular cartilage defect repair and has considerable potential for application as a biomaterial in cartilage tissue engineering.

Preparation and evaluation of gellan gum hydrogel reinforced with silk fibers with enhanced mechanical and biological properties for cartilage tissue engineering.

Various research about cartilage regeneration using biomaterials has been done recently. Particularly, gellan gum hydrogel (GG) is reported to be suitable as a biomaterial for cartilage tissue engineering (TE) for its water uptaking ability, producibility, and environmental resemblance of native cartilage. Despite these advantages, mechanical and cell adhesion properties are still difficult to modulate. Reinforcement is essential to overcome these problems. Herein, GG was modified by physically blending with different lengths of silk fiber (SF). As SF is expected to improve such disadvantages of GG, mechanical and biological properties were characterized to confirm its reinforcement ability. Mechanical properties such as degradation rate, swelling rate, compression strength, and viscosity were studied and it was confirmed that SF significantly reinforces the mechanical properties of GG. Furthermore, in vitro study was carried out to confirm morphology, biocompatibility, proliferation, and chondrogenesis of chondrocytes encapsulated in the hydrogels. Overall, chondrocytes in the GG blended with SF (SF/GG) showed enhanced cell viability and growth. According to this study, SF/GG can be a promising biomaterial for cartilage TE biomaterial.

Pluronic F-127/Silk Fibroin for Enhanced Mechanical Property and Sustained Release Drug for Tissue Engineering Biomaterial.

Herein, an injectable thermosensitive hydrogel was developed for a drug and cellular delivery system. The composite was prepared by facile physical mixing of pluronic F-127 (PF) and silk fibroin (SF) in an aqueous solution. The chemical structure, transparency, viscosity, injectability, degradation kinetic, cumulative release of dexamethasone (Dex), a type of corticosteroid drug, and size distribution of the fabricated hydrogels were characterized. Cytotoxicity of the hydrogels was also studied to verify the biocompatibility of the hydrogels. The addition of a proper amount of SF to PF not only improved the mechanical strength but also decreased the degradation rate which improved the fast rate release of hydrophobic drugs. The cytotoxicity of the hydrogel decreased when SF was added to PF in a proper amount. Overall, the results confirm that the composite of PF and SF can be a promising cell and drug delivery system for future application in tissue engineering and regenerative medicine.

Theranostic potential of biodegradable polymeric nanoparticles with paclitaxel and curcumin against breast carcinoma.

In this study, integrin-mediated targeting and near-infrared fluorescence (NIRF) traceable polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-PLGA)-based polymeric nanoparticles (NPs) were prepared to investigate the effects of paclitaxel (PTX) and curcumin (CUR) combination therapy on breast cancer. Cyclic (arginine-glycine-aspartic acid-phenylalanine-lysine) (cRGDfK) was selected as a ligand for breast cancer and conjugated to the end of NPs (cRGDfK-NPs). For fluorescence imaging, sulfo-cyanine 5.5 (Cy5.5) was incorporated into NPs (Cy5.5-NPs). A series of hybrid NPs consisting of NPs, cRGDfK-NPs, and Cy5.5-NPs with drugs encapsulated inside the core (Cy5.5-cRGDfK-NPs/PTX + CUR) were prepared by self-assembly. The efficacy of PTX and CUR combination and the ability of the integrin-mediated targeting of NPs were systemically investigated using a 4T1 mouse breast cancer cell line and a nude mouse xenograft model. We suggested that Cy5.5-cRGDfK-NPs/PTX + CUR has superior theranostic potential against breast carcinoma.

Suppression of Fibrotic Reactions of Chitosan-Alginate Microcapsules Containing Porcine Islets by Dexamethasone Surface Coating.

BACKGROUND: The microencapsulation is an ideal solution to overcome immune rejection without immunosuppressive treatment. Poor biocompatibility and small molecular antigens secreted from encapsulated islets induce fibrosis infiltration. Therefore, the aims of this study were to improve the biocompatibility of microcapsules by dexamethasone coating and to verify its effect after xenogeneic transplantation in a streptozotocin-induced diabetes mice. METHODS: Dexamethasone 21-phosphate (Dexa) was dissolved in 1% chitosan and was cross-linked with the alginate microcapsule surface. Insulin secretion and viability assays were performed 14 days after microencapsulation. Dexa-containing chitosan-coated alginate (Dexa-chitosan) or alginate microencapsulated porcine islets were transplanted into diabetic mice. The fibrosis infiltration score was calculated from the harvested microcapsules. The harvested microcapsules were stained with trichrome and for insulin and macrophages. RESULTS: No significant differences in glucose-stimulated insulin secretion and islet viability were noted among naked, alginate, and Dexa-chitosan microencapsulated islets. After transplantation of microencapsulated porcine islets, nonfasting blood glucose were normalized in both the Dexa-chitosan and alginate groups until 231 days. The average glucose after transplantation were lower in the Dexa-chitosan group than the alginate group. Pericapsular fibrosis and inflammatory cell infiltration of microcapsules were significantly reduced in Dexa-chitosan compared with alginate microcapsules. Dithizone and insulin were positive in Dexa-chitosan capsules. Although fibrosis and macrophage infiltration was noted on the surface, some alginate microcapsules were stained with insulin. CONCLUSION: Dexa coating on microcapsules significantly suppressed the fibrotic reaction on the capsule surface after transplantation of xenogenic islets containing microcapsules without any harmful effects on the function and survival of the islets.

Fucoxanthin Suppresses Osteoclastogenesis via Modulation of MAP Kinase and Nrf2 Signaling.

Fucoxanthin (FX), a natural carotenoid present in edible brown seaweed, is known for its therapeutic potential in various diseases, including bone disease. However, its underlying regulatory mechanisms in osteoclastogenesis remain unclear. In this study, we investigated the effect of FX on osteoclast differentiation and its regulatory signaling pathway. In vitro studies were performed using osteoclast-like RAW264.7 cells stimulated with the soluble receptor activator of nuclear factor-κB ligand or tumor necrosis factor-alpha/interleukin-6. FX treatment significantly inhibited osteoclast differentiation and bone resorption ability, and downregulated the expression of osteoclast-specific markers such as nuclear factor of activated T cells 1, dendritic cell-specific seven transmembrane protein, and matrix metallopeptidase 9. Intracellular signaling pathway analysis revealed that FX specifically decreased the activation of the extracellular signal-regulated kinase and p38 kinase, and increased the nuclear translocation of phosphonuclear factor erythroid 2-related factor 2 (Nrf2). Our results suggest that FX regulates the expression of mitogen-activated protein kinases and Nrf2. Therefore, FX is a potential therapeutic agent for osteoclast-related skeletal disorders including osteoporosis and rheumatoid arthritis.

Preparation and characterization of a soluble eggshell membrane/agarose composite scaffold with possible applications in cartilage regeneration.

Articular hyaline cartilage is an extremely hydrated, not vascularized tissue with a low-cell density. The damage of this tissue can occur after injuries or gradual stress and tears (osteoarthritis), minor damages can be self-healed in several weeks, but major injuries may eventually require surgery. In fact, in this case, because of nature of the cartilage (the absence of cells and vascularization) it is difficult to expect its natural regeneration in a reasonable amount of time. In recent years, cell therapy, in which cells are directly transplanted, has attracted attention. In this study, a scaffold for implanting chondrocytes was prepared. The scaffold was made as a sponge using the eggshell membrane and agarose. The eggshell membrane is structurally similar to the extracellular matrix and nontoxic due to its many collagen components and has good biocompatibility and biodegradability. However, scaffolds made of collagen only has poor mechanical properties. For this reason, the disulfide bond of collagen extracted from the insoluble eggshell membrane was cut, converted into water-soluble, and then mixed with agarose to prepare a scaffold. Agarose is capable of controlling mechanical properties, has excellent biocompatibility, and is suitable for forming a hydrogel having a three-dimensional porosity. The scaffold was examined for Fourier-transform infrared, mechanical properties, biodegradability, and biocompatibility. In in vitro experiment, cytotoxicity, cell proliferation, and messenger RNA expression were investigated. The study demonstrated that the agarose/eggshell membrane scaffold can be used for chondrocyte transplantation.