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The retinal pigment epithelium (RPE) plays a significant role in retaining structural integrity of eye. Factors such as reduction in cell regeneration due to aging and physical injury pose a major hurdle in RPE regeneration. In this study, we exploited the use of alginate (AGT) incorporated with Curcumin (CCI) forming a hydrogel based system CCI/AGT. The fabricated hydrogel could anchor RPE cell in it. In vitro cell analysis revealed that the CCI/AGT hydrogel shows good biocompatibility, enhanced cell growth ability and higher ECM formation compared to the pure AGT hydrogel. In particular, the presence of CCI in the hydrogels enhances the cells proliferation of the 23% respect to the pure alginate. Also the expression of crucial genes for retina functions and matrix production were positively affected by CCI presence, with an increment of 45% for RPE65, 32% for CRALBP and 26% for Collagen type 1. In vitro tests demonstrated the potential application of CCI/AGT hydrogels for transplantation under the sub-retinal space acting as a cell delivery vehicle and also their capability to provide an appropriate environment for RPE regeneration. These results suggest that CCI/AGT hydrogel could be translated into a potential surgical graft for biological implantation of retinal tissue engineering.

Telmisartan (TS) have developed for the treatment of hypertension as the angiotensin II receptor blocker. TS belongs to class II drug in BCS classification and it has good permeability. But, it is poorly water soluble. Biological half-life of TS is 24 hours because it has not good bioavailability (only 42∼58%). The absorption of a drug is often limited by dissolution rate. Drug dissolution is important factor to the therapeutic efficacy of a medicine. Therefore, TS requires alternative methods of drug delivery system to improve solubilization. In this study, we have prepared solid dispersions (SD) of the TS, polyvinylpyrrolidone (PVP) K-30 using rotary evaporation to promote release rate. So, we made sustained release formulation to make that is continually released and reduced the number of administration to patients. We selected the methods which are wet granulation (WG) and vitrification (VT) for sustained release. WG is a common techinique in the pharmaceutical industry that is mixing the powder to make bonds between powder particles using water. VT is techinique that transforms the crystalline particle into amorphous state using cryomilling. We measured the characterization of SD that was performed using various methods to analyze the structure of powder sample. Characterizations of SD were performed to analyze the surface by scanning electron microscopy. The crystallinity and molecular structure are analyzed by Fourier transform infrared spectroscopy, powder X-ray diffractometer. Also, thermal porperties are analyzed by differential scanning calorimeter. In vitro dissolution test assessed by RP-HPLC to analyze dissolution rate of sustained release formulation and solid dispersion. In this results, these indicate that both methods improve solubility and dissolution rate. The drug solubility of processed VT almost greater than the pure drug and WG. And, in Bats, VT 3 has higher dissolution rates than others. So, this results are useful to improve TS in the pharmaceutical industry.

Recently, in tissue engineering gellan gum as a polysaccharide composed of glucose, glutaric acid, and rhamnose is proposed as a substitute for cartilage regeneration applications. Silk fibroin has biocompatibility, biodegradability and excellent mechanical properties. In this work, to confirm the e...

합성고분자인 poly(lactic-co-glycolic acid)(PLGA)는 우수한 생분해능을 가진 생체재료로서 널리 이용되고 있으며, 천연유래 고분자인 실크와 소장 점막하 조직, 탈 미네랄화 골분 그리고 오리발 유래의 콜라겐은 생체 적합한 특성을 가지고 있다. 본 논문에서는 여러 가지 천연유래 고분자를 함유한 PLGA를 제작한 후, 지지체의 물성 및 표면을 확인하였으며 토끼 골수유래줄기세포를 이용하여 지지체에 파종 후, 세포의 생존율과 세포분화 정도를 측정하였고 in vivo 실험에서 면역조직학적 염색인 H&E와 Von Kossa을 실시하여 골분화 정도를 확인하였다. 결과적으로 오리발 유래 콜라겐과 소장 점막하 조직을 함유한 지지체에서 빠른 골 분화의 모습을 확인할 수 있었다.

Tissue engineered bone substitutes should mimic natural bone characteristics to be highly-suitable for treating bone defects in addition to its biocompatibility and good mechanical stability. In this study, we performed a detailed in vivo bone regeneration evaluation of 80 wt% duck’s feet collagen/poly(lactide-co-glycolide) scaffolds (DC/PLGA) fabricated by solvent casting/salt leaching strategy in a rat calvarial defect as model. We have already shown a strong influence of DC/ PLGA scaffolds on bone regeneration in terms of biomaterial cohesion, architecture, mechanical features, and in vitro biological properties. The as-fabricated scaffold has shown significant increase in osteogenesis, initial bone formation and differentiation, ascribed to the high percentage of DC in the 80 wt% DC/PLGA scaffold. The in vivo implanted scaffold was found be well-attached to the bone defect region and eventually gets integrated with the surrounding tissues without any pronounced inflammatory reactions. Compared to bare PLGA, an increased recovery in bone volume was observed at 8th week post-surgery. Thus, the 80 wt% DC/PLGA scaffold can be envisioned as a potential alternative bone graft in bone tissue engineering.

"First published:24 February 2020", Exosomes (EXs) are nanocarrier vesicles with 20â 50â nm dimensions. They are involved in cell proliferation and differentiation and in protecting the integrity of materials. They can be isolated from plasma and immunoreactive components. Recent studies demonstrated their potential role in cartilage regeneration. To enhance their regenerative effect, molecules like microRNA (miRâ 140) can be loaded in EX that acts as RNA delivery systems. In this study, we combined EX with miRâ 140 to enhance cell differentiation by inducing membrane fusion and consequent miRNA released into the cytoplasm. The carrier RNA complex was successfully synthesized through freeze and thaw method leading to the formation of EXâ containing miRâ 140. The EX morphology was assessed through transmission electron microscopy and their miRâ 140 uptake efficiency through realâ time polymerase chain reaction (RTâ PCR). The effects on bone marrow stem cells (BMSCs) were evaluated by in vitro cell culture. Cell adhesion and morphology were studied using a bioâ scanning electron microscope and confocal laser scanning microscope. Differentiation BMSCs into chondrocytes was analyzed by RTâ PCR and histology. Our results confirm the bioactive role of EX loaded with miRâ 140 in the differentiation of BMSCs into chondrocytes. EXs were biocompatible involving in the cartilage healing process through chromogenic differentiation of BMCS exploiting the tissue engineering route., This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF‐ 2017R1A2B3010270) and a grant of the Korea Health Technology R&D Project (HI15C2996) through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea.

It remains controversial whether certain treatments should apply to HCC patients with ascites due to concerns about worsening liver function. The objective of the present study is to compare the prognostic performance of 4 liver function models currently in use for HCC patients with ascites. A total of 437 treatment-naïve, newly diagnosed HCC patients were analyzed. The predictive performance of Child-Pugh, MELD, MELD-Na, and ALBI scores were examined using ROC curve analysis. MELD-Na score showed good performance in predicting 1-, 2-, and 3-year mortality, particularly 1-year mortality. MELD-Na score significantly increased at 30 days after treatment in cases initially receiving best supportive care (14–17, p p p = .021). For patients with advanced tumor stage and MELD-Na score ≥12, HCC-specific treatment did not offer significantly better prognosis compared with only the best supportive care (median survival: 2.2 vs. 1.8 months for HCC-specific treatment vs. best supportive care, p = .15). MELD-Na can effectively identify liver functional reserve and prognosis in HCC patients with ascites. MELD-Na, together with the tumor stage, may help establish a therapeutic strategy for them.

Collagen is an important component that makes 25–35% of our body proteins. Over the past decades, tissue engineers have been designing collagen-based biocompatible materials and studying their applications in different fields. Collagen obtained from cattle and pigs has been mainly used until now, but collagen derived from fish and other livestock has attracted more attention since the outbreak of mad cow disease, and they are also used as a raw material for cosmetics and foods. Due to the zoonotic infection using collagen derived from pigs and cattle, their application in developing biomaterials is limited; hence, the development of new animal-derived collagen is required. In addition, there is a religion (Islam, Hinduism, and Judaism) limited to export raw materials and products derived from cattle and pig. Hence, high-value collagen that is universally accessible in the world market is required. Therefore, in this review, we have dealt with the use of duck’s feet-derived collagen (DC) as an emerging alternative to solve this problem and also presenting few original investigated bone regeneration results performed using DC.

Treatment for the osteochondral defects (ODs) is more challenging nowadays that needs to be addressed by developing alternative bone tissue engineering materials. Gellan gum (GG) is a widely used natural polysaccharide in the field of tissue engineering (TE) and regenerative medicine due to its versatile properties. There are many reports about the successful application of GG in cartilage tissue engineering and guiding bone formation. Functional coatings and porous composite materials have been introduced in next-generation materials for treating OD, whereas osteoconductive materials, such as demineralized bone particle (DBP) or bone derivatives, are used. However, modification of porosity, biocompatibility, cell proliferation, and mechanical properties is needed. DBP can activate human mesenchymal stem cells to differentiate into osteoblast cells. In this chapter, the potential application of GG with DBP in different combinations was reviewed, and the best suitable combinations were selected and further studied in small animal models for the soft and hard tissue engineering applications; also its application in the osteochondral integration fields were briefly discussed.

Treating critical-sized bone defects is an important issue in the field of tissue engineering and bone regeneration. From the various biomaterials for bone regeneration, collagen is an important and widely used biomaterial in biomedical applications, hence, it has numerous attractive properties including biocompatibility, hyper elastic behavior, prominent mechanical properties, support cell adhesion, proliferation, and biodegradability. In the present study, collagen was extracted from duck's feet (DC) as a new collagen source and combined with quercetin (Qtn), a type of flavonoids found in apple and onions and has been reported to affect the bone metabolism, for increasing osteogenic differentiation. Further, improving osteoconductive properties of the scaffold hydroxyapatite (HAp) a biodegradable material was used. We prepared 0, 25, 50, and 100 μM Qtn/DC/HAp sponges using Qtn, DC, and HAp. Their physiochemical characteristics were evaluated using scanning electron microscopy, compressive strength, porosity, and Fourier transform infrared spectroscopy. To assess the effect of Qtn on osteogenic differentiation, we cultured bone marrow mesenchymal stem cells on the sponges and evaluated by alkaline phosphatase, 3-4-2, 5-diphenyl tetrazolium bromide assay, and real-time polymerase chain reaction. Additionally, they were studied implanting in rat, analyzed through Micro-CT and histological staining. From our in vitro and in vivo results, we found that Qtn has an effect on bone regeneration. Among the different experimental groups, 25 μM Qtn/DC/HAp sponge was found to be highly increased in cell proliferation and osteogenic differentiation compared with other groups. Therefore, 25 μM Qtn/DC/HAp sponge can be used as an alternative biomaterial for bone regeneration in critical situations.

Hydrogels have shown to be advantageous in supporting damaged cartilage because of its analogous to the extracellular matrix (ECM) of cartilage tissue. However, problems such as infection and inflammation are still a challenge to be solved. In terms of tissue engineering, natural materials are more advantageous than synthetic materials in biocompatibility and biodegradability status. Herein, physically blended nature-derived gellan gum (GG) hydrogel and hyaluronic acid (HA) hydrogel is suggested as a one of solution for cartilage tissue engineering material. The purpose of this study is to determine the effect of GG/HA hydrogel in vitro and in vivo. The chemical and mechanical properties were measured to confirm the compatibility of hydrogels for cartilage tissue engineering. The viability, proliferation, morphology, and gene expression of chondrocytes encapsulated in hydrogels were examined in vitro. Furthermore, the beneficial effect of the blended hydrogel was confirmed by performing the in vivo experiment. The chemical properties of hydrogels confirmed the well physically blended hydrogels. The mechanical studies of hydrogels displayed that as the content of HA increases, the swelling ratio was higher, compressive strength decreased and degradation was faster. Therefore, to use the hydrogel of GG and HA network, the proper amount must be blended. The in vitro study of chondrocytes encapsulated GG/HA hydrogel showed that the proper amount of HA enhanced the cell growth, attachment, and gene expression. The in vivo examination verified the advantageous effect of GG/HA hydrogel. Overall results demonstrate that GG/HA hydrogel is suitable for culturing chondrocyte and can be further applied for the treatment of cartilage defects.

Scaffolds, used for tissue regeneration are important to preserve their function and morphology during tissue healing. Especially, scaffolds for bone tissue engineering should have high mechanical properties to endure load of bone. Silk fibroin (SF) from Bombyx mori silk cocoon has potency as a type of biomaterials in the tissue engineering. β-tricalcium phosphate (β-TCP) as a type of bioceramics is also critical as biomaterials for bone regeneration because of its biocompatibility, osteoconductivity, and mechanical strength. The aim of this study was to fabricate three-dimensional SF/β-TCP scaffolds and access its availability for bone grafts through in vitro and in vivo test. The scaffolds were fabricated in each different ratios of SF and β-TCP (100:0, 75:25, 50:50, 25:75). The characterizations of scaffolds were conducted by FT-IR, compressive strength, porosity, and SEM. The in vitro and in vivo tests were carried out by MTT, ALP, RT-PCR, SEM, μ-CT, and histological staining. We found that the SF/β-TCP scaffolds have high mechanical strength and appropriate porosity for bone tissue engineering. The study showed that SF/β-TCP (75:25) scaffold exhibited the highest osteogenesis compared with other scaffolds. The results suggested that SF/β-TCP (75:25) scaffold can be applied as one of potential bone grafts for bone tissue engineering.

A number of polysaccharides exhibit pharmacological activities. Polysaccharides derived from Inonotus obliquus (PLIO) appear to have various potential pharmacological properties, including anti‑tumor activity. However, the molecular mechanisms underlying these properties remain to be elucidated. The present study investigated the anti‑metastatic potential of PLIO and the underlying signaling pathways in B16‑F10 murine melanoma cells using the MTT colorimetric assay, in vitro migration and invasion assays, and flow cytometric and western blot analyses. PLIO inhibited the invasion of B16‑F10 cells and suppressed the expression of matrix metalloproteinases. PLIO treatment inhibited nuclear factor‑κB (NF‑κB) nuclear translocation in B16‑F10 cells. In addition, PLIO treatment inhibited the phosphorylation of c-Jun N‑terminal kinases and AKT. These results suggest that PLIO may suppress the invasion of highly metastatic melanoma cells via inhibition of the AKT/NF-κB signaling pathways.

Tissue engineered biomaterials have biodegradable and biocompatible properties. In this study, we have fabricated sponges using duck's feet derived collagen (DC) and gellan gum (GG), and further studied its inflammatory responses. The as-prepared duck's feet DC/GG sponges showed the possibility of application as a tissue engineering material through in vitro and in vivo experiments. The physical and chemical properties of sponges were characterized by compression strength, porosity, and scanning electron microscopy, etc. In vitro cell viability were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. An inflammatory response was studied after seeding RAW264.7 cells on as-fabricated sponges using reverse transcriptase-polymerase chain reaction. In vivo studies were carried out by implanting in subcutaneous nude mouse followed by extraction, histological staining. Collectively, superior results were showed by DC/GG sponges than GG sponge in terms of physical property and cell proliferation and thus can be considered as a potential candidate for future tissue engineering applications., This work was supported by Technology Commercialization Support Program [grant number 814005- 03-2-HD020], Ministry for Food, Agriculture, Forestry and Fisheries (MIFAFF) and grant of the Korea Health Technology R&D Project through the KHIDI [grant number HI15C2996], Ministry of Health and Welfare (MOHW), Republic of Korea.

In this study, porcine small intestinal submucosa (SIS) without immune response were used to make SIS/PLGA scaffolds with different SIS content i.e. 0, 10, 20, 40, and 80 wt%. Further, the attachment and proliferation of costal cartilage cells (CCs) in SIS/PLGA scaffolds were characterized. Glycosaminoglycan (sGAG) and collagen contents assay were conducted to verify the effects of SIS on extracellular matrix (ECM) formulation. The CCs specific gene expression was confirmed by polymerase chain reaction (PCR). In conclusion, the sGAG production was formed to be higher in the 20 wt% SIS/PLGA scaffolds, which showed enhanced CCs cell growth and proliferation compared with other scaffolds.

In this study, we have designed scaffold by mixing collagen extracted from the duck’s flippers with poly(vinyl alcohol) (DC/PVA) via freeze-thawing and the as-prepared scaffold were evaluated for skin regeneration. The physical and chemical properties of the scaffolds were characterized using FTIR, SEM, compressive strength, degree of swelling, etc. The in vitro behavior (cell proliferation) was examined after cultured with fibroblasts through the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The in vivo results demonstrated that the scaffolds implanted in rat induced full-thickness defect, confirmed by histological staining. Encompassing all results, the DC/PVA scaffolds can be anticipated as efficient platforms for skin regeneration facilitating required cell adhesion, growth and proliferation.

Collagen constituting the extracellular matrix has been widely used as biocompatible material for human use. In this study, we have selected duck's feet for extracting collagen. A simple method not utilizing harsh chemical had been employed to extract collagen from duck's feet. We fabricated duck's feet collagen/silk hybrid scaffold for the purpose of modifying the degradation rate of duck's feet collagen. This study suggests that extracted collagen from duck's feet is biocompatible and resembles collagen extracted from porcine which is commercially used. Duck's feet collagen is also economically feasible and it could therefore be a good candidate as a tissue engineering material. Further, addition of silk to fabricate a duck's feet collagen/silk hybrid scaffold could enhance the biostability of duck's feet collagen scaffold. Duck's feet collagen/silk scaffold increased the cell viability compared to silk alone. Animal studies also showed that duck's feet collagen/silk scaffold was more biocompatible than silk alone and more biostable than duck's feet or porcine collagen alone. Additionally, the results revealed that duck's feet collagen/silk hybrid scaffold had high porosity, cell infiltration and proliferation. We suggest that duck's feet collagen/silk hybrid scaffold could be used as a dermal substitution for full thickness skin defects.

Every day, numerous surgical procedures are performed worldwide to repair or replace tissues damaged by disease or trauma. Tissue engineering aims to develop neotissue by combining appropriate cells with a three-dimensional scaffold template, which eliminated the need for lifelong anticoagulation medication and prevents durability and reoperation issues. This article describes various hybrid materials used to develop state-of-the-art, three-dimensional scaffolds in bone tissue engineering and regenerative medicine.

Tissue engineering and regenerative medical therapy aims to create functional tissue grafts capable of regenerating/replacing defective or damaged tissues and organs for transplantation. Biomaterial matrices play the key role to provide three-dimensional templates for tissue regeneration by mimicking the extracellular matrix which includes required adhesion sites and growth factors for cell attachment and further development. In this article, we outline various biomimetic materials and approaches employed for designing smart scaffold systems for regeneration of tissues/organs.

Regeneration of diseased or damaged skeletal tissues is one of the challenge that needs to be solved. Although there have been many bone tissue engineering developed, scaffold-based tissue engineering complement the conventional treatment for large bone by completing biological and functional environment. Among many materials, silk fibroin (SF) is one of the favorable material for applications in bone tissue engineering scaffolding. SF is a fibrous protein mainly extracted from Bombyx mori. and spiders. SF has been used as a biomaterial for bone graft by its unique mechanical properties, controllable biodegradation rate and high biocompatibility. Moreover, SF can be processed using conventional and advanced biofabrication methods to form various scaffold types such as sponges, mats, hydrogels and films. This review discusses about recent application and advancement of SF as a biomaterial.

There is a significant rise in the bone grafts demand worldwide to treat bone defects owing to continuous increase in conditions such as injury, trauma, diseases, or infections. Therefore, development of three-dimensional scaffolds has evolved as a reliable technology to address the current limitations for bone tissue regeneration. Mimicking the natural bone, in this study, we have designed a silk fibroin/hydroxyapatite scaffold inlaid with a bioactive phytochemical (quercetin) at different concentrations for promoting osteogenesis, especially focusing on quercetin ability for enhancing bone health. Characterization of the quercetin/silk fibroin/hydroxyapatite (Qtn/SF/HAp) scaffolds showed an increased pore size and irregular porous microstructure with good mechanical strength. The Qtn (low-content)/SF/HAp scaffold was found to be an efficient cell carrier facilitating cellular growth, osteogenic differentiation, and proliferation as compared to SF/HAp and Qtn (high-content)/SF/HAp scaffolds. However, Qtn (high-content)/SF/HAp was observed to inhibit cell proliferation without any effects on cell viability. In vitro and in vivo outcomes studied using bone marrow-derived mesenchymal stem cells (rBMSCs) confirm the cytocompatibility, osteogenic differentiation ability, and prominent upregulation of the bone-specific gene expressions for the rBMSCs-seeded Qtn/SF/HAp scaffolds. In particular, the implanted Qtn (low-content)/SF/HAp scaffolds at the bone defect site were found to be well-attached and amalgamated with the surrounding tissues with approximately 80% bone volume recovery at 6 weeks after surgery as compared with other groups. Based on the aforementioned observations highlighting the quercetin efficiency for bone regeneration, the as-synthesized Qtn (low-content)/SF/HAp scaffolds can be envisioned to provide a biomimetic bone-like microenvironment promoting rBMSCs differentiation into osteoblast, thus suggesting a potential alternative graft for high-performance regeneration of bone tissues.

Several concentrations of saponin (Sa), which is water-soluble, were fabricated well with gellan gum (GG) solution. Sa, found in many plants like clematis and ginseng, has long been used in traditional chinese medicine to treat joint diseases including osteoarthritis. Also it has its ability of anti-inflammatory, antioxidant and anti-cancer. GG hydrogel is suitable as a cell encapsulating agent in the field of cartilage regeneration because of its easy processing and biocompatibility. In this study, GG hydrogel scaffolds with different concentration of Sa were conducted for analysis by SEM, FT-IR, compressive strength, water uptake, degradation rate, MTT assay, mRNA expression. It was observed that 0.025 wt% Sa/GG hydrogel scaffold shows good morphology, cell proliferation and mRNA expression results. The composite material supports cell growth covered with extracellular matrix (ECM) with maintaining its function. As a result, incorporation of Sa loaded with GG hydrogel scaffolds had positive result up to 0.025 wt% in cartilage regeneration., This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C2996)., info:eu-repo/semantics/publishedVersion

The aim of this study was to investigate the effects of silk fibroin scaffold, a natural biodegradable polymer scaffold, on the adhesive and proliferative behaviors of chondrocytes. Various silk fibroin scaffolds were produced using the salt extraction method, and scaffolds with different pore sizes (90-180, 180-250, 250-355, and 355-425 μm) were constructed based on the size of the salt particles. Chondrocytes were seeded on the scaffolds and incubated. The produced scaffolds were analyzed with Fourier transform-infrared spectroscopy and exhibited characteristics similar to those of natural silk in terms of chemical composition and structure. Moreover, we found that the mechanical strength decreased as the pore size increased. Scanning electron microscopy images confirmed the existence of pores in the silk fibroin scaffold. Additionally, scaffolds with smaller pore sizes facilitated improved cell adhesion. Using MTT analysis, we found that scaffold with pore sizes of 90-180 and 180-250 μm provided the best environment for cell proliferation. The amount levels of sulfated glycosaminoglycan (sGAG) and collagen were highest for scaffolds with a pore size of 90-180 μm. In gene expression analysis, scaffolds with pore sizes of 90-180 and 180-250 μm showed the highest expression of the chondrocytes marker aggrecan and type II collagen. Collectively, these data suggest that silk fibroin scaffolds with smaller pore sizes (90-250 μm) provide the best environment for adhesion and proliferation of chondrocytes. Open image in new window

Regeneration of diseased or damaged skeletal tissues is one of the challenge that needs to be solved. Although there have been many bone tissue engineering developed, scaffold-based tissue engineering complement the conventional treatment for large bone by completing biological and functional environment. Among many materials, silk fibroin (SF) is one of the favorable material for applications in bone tissue engineering scaffolding. SF is a fibrous protein mainly extracted from Bombyx mori. and spiders. SF has been used as a biomaterial for bone graft by its unique mechanical properties, controllable biodegradation rate and high biocompatibility. Moreover, SF can be processed using conventional and advanced biofabrication methods to form various scaffold types such as sponges, mats, hydrogels and films. This review discusses about recent application and advancement of SF as a biomaterial.

It is well known that Phellinus linteus, which produces hispidin and its derivatives, possesses antioxidant activities. In this study, we investigated whether hispidin has protective effects on palmitate-induced oxidative stress in C2C12 skeletal muscle cells. Our results showed that palmitate treatment in C2C12 myotubes increased ROS generation and cell death as compared with the control. However, pretreatment of hispidin for 8 h improved the survival of C2C12 myotubes against palmitate-induced oxidative stress via inhibition of intracellular ROS production. Hispidin also inhibited palmitate-induced apoptotic nuclear condensation in C2C12 myotubes. In addition, we found that hispidin can suppress cleavage of caspase-3, expression of Bax, and NF-κB translocation. Therefore, these results suggest that hispidin is capable of protecting C2C12 myotubes against palmitate-induced oxidative stress.

An ideal tissue-engineered scaffold must provide sufficient porosity to allow free movement of cells, nutrients, and oxygen for proper cell growth and further maintenance. Owing to variation in pore sizes and shapes of as-fabricated scaffold, the amount of oxygen available for the cells attached to the scaffold and transfer of by-products and excrement will be different, which ultimately results in cell activity. Thus, optimizing pore size and porosity of a scaffold for a specific tissue regeneration are one of the key highlights, which should be considered while designing a scaffold as well as choosing a specific cell type. In this study, three-dimensional (3D) scaffolds based on blends of duck's feet collagen (DC) and poly (lactic-co-glycolic acid) (PLGA) with different pore sizes i.e. 90-180, 180-250, 250-355 and 355-425 μm were prepared using solvent casting/salt leaching approach and examined its effects on chondrification. The morphological analysis of the as-fabricated scaffolds was performed using SEM for studying porosity and pore size. The cell proliferation and gene expression were investigated after culturing costal chondrocytes on each scaffolds using 3-(4, 5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and qRT-PCR. Histological staining of in vivo implants was performed in nude mice as models. The biological evaluation showed a pore-size dependent chondrification at different time points. Especially, the 355-425 μm DC/PLGA scaffold showed a highest positive impact on maintenance of cell proliferation, costal chondrocyte phenotype and increased glycosaminoglycan accumulation than the other groups. These results indicated that DC/PLGA scaffolds with pore size ranging from 250 to 425 μm can be considered as highly-suitable constructs for enhanced chondrification.

Background/aims: It is unclear whether chronic hepatitis B (CHB) patients with antiviral resistance, who achieve a complete virologic response (CVR) with tenofovir disoproxil fumarate (TDF) and nucleoside analogue (NUC) combination therapy, maintain CVR if switched to TDF monotherapy. We investigated the persistence of CVR after cessation of NUC in virologically suppressed antiviral resistant CHB patients using TDF + NUC combination therapy. Methods: This study recruited 76 antiviral resistant CHB patients showing CVR on TDF + entecavir (ETV) (n = 52), TDF + lamivudine (LAM; n = 14) and TDF + telbivudine (LdT; n = 10) combination therapy, who were switched to TDF monotherapy as step-down therapy. Results: At baseline, 47 patients were male and the median age was 53.0 years (range: 30-78 years); 72.3% cases were hepatitis B e antigen-positive (HBeAg+) and 23.7% were of liver cirrhosis. The median duration of TDF + NUC combination therapy was 20.8 months (range: 3-46 months). At a median follow-up of 24.7 months (range: 12-48 months) after switching to TDF monotherapy, all 76 patients maintained CVR, regardless of the duration of combination therapy and the type of prior NUC and antiviral resistance. Renal dysfunction was not observed during the treatment period. Conclusions: The step-down strategy of switching from TDF + NUC combination therapy to TDF monotherapy in virologically suppressed CHB patients with antiviral resistance should be considered. This article is protected by copyright. All rights reserved

The ZnO nanoneedles (ZNNs) were grown in large quantity by thermal evaporation technique on non-catalytic Si (100) substrates and used as an effective photocatalyst for photocatalytic degradation of methyl orange dye (MO). The detailed characteristics of ZNNs confirmed that the synthesized nanostructures are grown in high density and exhibit well-crystallinity with good optical properties. The photocatalytic properties of ZNNs were investigated under UV light irradiation. A fast decomposition of the MO dye was observed with a degradation rate of ~95.4% within 140 min.

The aim of the study was to investigate the effects of small intestinal submucosa (SIS) sponges, a natural biodegradable polymer scaffold, on the adhesion behavior and the proliferation of Schwann cells (SCs). SIS sponges were prepared by varying the contents of SIS powders (1%, 2%, and 3% SIS concentration) and SCs were seeded on the sponges and incubated to investigate the adhesion and proliferation of SCs. A series of analytical process was conducted to observe the water absorption rate of sponges and confirmed the proliferation and morphology of SCs by scanning electron microscopy (SEM), 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, reverse transcription polymerase chain reaction (RT-PCR), and histological evaluation. The best adhesion behavior and the proliferation of SCs were observed on the sponge with 2% powder content. Also, analysis of messenger ribonucleic acid (mRNA) expression using the neuron-specific enolase (NSE) and neurofilament protein (NF) nerve markers showed that SC gene expression was excellent in the 2% SIS sponge. In vivo hematoxylin and eosin (H&E) staining and immunofluorescence results showed that cells and tissue formed well in the pores of sponges with 2% and 3% SIS powder contents, compared with formation in the 1% SIS sponge. The SIS sponges provided an unsuitable habitat for the adhesion and proliferation of cells in that the pore size was small. In this study, the adhesion behavior and the proliferation could be changed depending on the pore size and SIS powder content in the sponges. Thus, an appropriate powder content of SIS should be used to prepare SIS sponge scaffolds.

The retinal pigment epithelium (RPE) plays a critical role in the maintenance of the normal functions of the retina, particularly the photoreceptors. RPE dysfunction, vision loss and degeneration have been implicated as the cause of many retinal diseases, including retinitis pigmentosa and age-related macular degeneration (AMD). To overcome such disorders, tissue engineering could offer useful strategies, using biodegradable polymeric films to replace diseased or lost RPE. Synthetic/natural hybrid films have been studied as a temporary substrate for growing RPEs in biological implantations. In this study, we prepared small intestinal submucosa (SIS)-poly(lactic-co-glycolic) (PLGA) hybrid films and seeded human RPE cells (ARPE-19 cells) onto the film surface. We investigated the film suitability for RPE cell proliferation by MTT assay. The morphology of cellular adhesion on the film was confirmed by scanning electron microscopy (SEM). Reverse transcription-polymerase chain reaction (RT-PCR) and 3-amino-9-ethylcarbazole (AEC) staining were performed to examine mRNA expression and to compare cell proliferation on the films, using cytokeratin as a marker of RPE. Conclusively, we confirmed the higher cell survival rate and much stronger phenotype expression of RPEs on SIS-PLGA films compared to pure PLGA films. These results demonstrated the potential application of SIS-PLGA films in tissue-engineering strategies. Copyright © 2014 John Wiley & Sons, Ltd.

Demineralized bone particles (DBP) and alginate hybrid sponges were fabricated at 10, 20, 40 and 80% DBP/alginate hybrid ratios for seeding chondrocyte. Cell proliferation was measured via MTT assay. Morphological observation, histology, biological assay and RT-PCR were performed at each time point 1, 2 and 3 weeks. The cell viability was better in 20% DBP/alginate sponges than in other sponges. SEM results showed that more attached and more proliferated cells in the 20% DBP/alginate sponges with the lapse of time. Finally, histochemical assay results showed that the phenotype of chondrocyte was well maintained and both acidic mucopolysaccharide and type II collagen was well formed at 20% sponges. This study suggested that DBP/alginate sponge may serve as a potential cell delivery vehicle and a structural basis for tissue engineered articular cartilage.

Over the past few decades, gellan gum (GG) has attracted substantial research interest in several fields including biomedical and clinical applications. The GG has highly versatile properties like easy bio-fabrication, tunable mechanical, cell adhesion, biocompatibility, biodegradability, drug delivery, and is easy to functionalize. These properties have put forth GG as a promising material in tissue engineering and regenerative medicine fields. Nevertheless, GG alone has poor mechanical strength, stability, and a high gelling temperature in physiological conditions. However, GG physiochemical properties can be enhanced by blending them with other polymers like chitosan, agar, sodium alginate, starch, cellulose, pullulan, polyvinyl chloride, xanthan gum, and other nanomaterials, like gold, silver, or composites. In this review article, we discuss the comprehensive overview and different strategies for the preparation of GG based biomaterial, hydrogels, and scaffolds for drug delivery, wound healing, antimicrobial activity, and cell adhesion. In addition, we have given special attention to tissue engineering applications of GG, which can be combined with another natural, synthetic polymers and nanoparticles, and other composites materials. Overall, this review article clearly presents a summary of the recent advances in research studies on GG for different biomedical applications.

The purpose of this study is to produce injectable taurine (Tr)-loaded alginate (Agn) hydrogel for age-related macular degeneration (AMD) treatment by inducing the regeneration of RPE (retinal pigment epithelium) cells. Porosity and swelling ratio were measured to evaluate the mechanical properties of the hydrogels, and Fourier transform infrared spectroscopy (FTIR) was used to evaluate the physical and chemical properties. RPE cells extracted from the pigmented epithelium of rabbits were encapsulated in the Tr/Agn hydrogels. Cells proliferation and migration were improved in Tr/Agn hydrogels with an enhanced expression of RPE-specific genes including RPE65, CRALBP, NPR-A, MITF and collagen type I and II. In vivo tests demonstrated the excellent biocompatibility and biodegradability without inflammatory response by the host when implanted with the hydrogel. Moreover, when the Tr/Agn hydrogels were injected into the sub-retinal space, high adhesion of RPE cells and retinal regeneration were confirmed. These results demonstrated a potential role of injectable Tr/Agn hydrogels as potential therapeutic tools for the treatment of retinal diseases, including AMD.

There are two distinct subtypes of autoimmune pancreatitis (AIP): type 1 and type 2. Type 1 AIP is the pancreatic manifestation of systemic fibroinflammatory disease, which is named as IgG4-related disease. On the other hand, type 2 AIP is a pancreatic disorder that is not associated with IgG4. Type 1 and type 2 AIP have different clinical profiles and histologic findings. We present a 22-year-old man who has been diagnosed as type 1 AIP with histologically proven granulocytic epithelial lesion after surgical resection for pancreatic head mass. Since the patient had no pancreatic duct narrowing, elevation of serum IgG4, and other organ involvement, it was very difficult to diagnose preoperatively. This is a rare and interesting case in which histologic features of type 1 and type 2 AIP coexist.

This study investigated the influence of pore sizes of poly(lactic-co-glycolic acid) (PLGA) scaffolds on the compressive strength of tissue-engineered biodiscs and selection of the best suitable pore size for cells to grow in vivo. PLGA scaffolds were fabricated by solvent casting/salt-leaching with pore sizes of 90-180, 180-250, 250-355 and 355-425 µm. Nucleus pulposus (NP) cells were seeded on PLGA scaffolds with various pore sizes. Each sample was harvested at each time point, after retrieval of PLGA scaffolds seeded with NP cells, which were implanted into subcutaneous spaces in nude mice at 4 and 6 weeks. MTT assay, glycosaminoglycan (GAG) assay, haematoxylin and eosin (H&E) staining, safranin O staining and immunohistochemistry (for collagen type II) were performed at each time point. As the pores became smaller, the value of the compressive strength of the scaffold was increased. The group of scaffolds with pore sizes of 90-250 µm showed better cell proliferation and ECM production. These results demonstrated that the compressive strength of the scaffold was improved while the scaffold had pore sizes in the range 90-250 µm and good cell interconnectivity. Suitable space in the scaffold for cell viability is a key factor for cell metabolism. Copyright © 2014 John Wiley & Sons, Ltd.

There are many dystrophies related corneal endothelium resulting in edema, loss of transpar-ency and blindness, finally. Currently, transplantation is only surgical treatment for patients withthese corneal endothelial dystrophies, however, the limitation of transplantation is the absolutedeficiency of donor cornea. Very recently, to overcome this issue of limited supply of donorcornea, regenerative medicine including stem cell therapy and tissue engineering has been widelyattempted and success for human clinical trial. In this review, recent advances for the regeneration of corneal endothelial cell (CEnC) as (1)iso-lation and culture methods of CEnC for the somatic cell source, (2)stem cell source for CEnC asembryonic, induce pluripotent stem cell (iPS) and adult stem cell, (3)tissue engineering tech-niques as cell sheet engineering and development of scaffold materials and finally (4)the appli-cation of silk as a biomaterial for cornea by our laboratory have been introduced.Rec.12/3/2013, Acc.1/7/2014, pp4-14

In this study, we manufactured a polymer blend, using hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), by spray drying method to improve the characteristics of polymers. This polymer blend was used to improve the drug delivery of cilostazol, a phosphodiesterase inhibitor that decreases serum triglycerides, is a direct arterial vasodilator, and inhibits platelet aggregation and smooth muscle cell proliferation. Compatibility with this drug was achieved when the polymer blend of HPMC and PVP were spray dried. Various ratios of the two ingredients were blended to determine optimum release rate of this poorly soluble drug. Cilostazol blended with different ratios of HPMC and PVP was analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to confirm surface morphology and combination of drug and polymer. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were conducted to confirm thermodynamic properties and chemical structure change, respectively. Change in the drug release of cilostazol was expected by adjusting the HPMC and PVP blend ratio in gastric juice (pH 1.2). Open image in new window

Intervertebral disc (IVD) degeneration is an age-related process that affects the biomechanical properties of the spine and is assumed to be one of the principal causes of low back pain. Poly(lactide-co-glycolide) (PLGA) and hyaluronic acid (HA) have been widely used as biocompatible scaffold materials for tissue regeneration. In the present study, we fabricated a microporous PLGA scaffold by the salt-leaching method and HA-loaded PLGA scaffolds by the penetrating method. As the porosity of PLGA and PLGA/HA is 90.7% and 96.5%, respectively, PLGA/HA scaffold has the higher porosity. However, the pore size of PLGA (240.7±14.0 μm) is the larger than HA/PLGA (212.0±12.5 μm), and cells from the annulus fibrosus (AF) were seeded into the scaffolds. For the in vivo study, the PLGA and HA/PLGA scaffolds were implanted in four-week-old nude mice. All scaffolds were characterized using a scanning electron microscope (SEM), and the amounts of glycosaminoglycan (GAG) and collagen in the scaffolds were determined by a spectrophotometer. Histological evaluation indicated the higher level of AF cell proliferation in the HA/PLGA scaffold than in PLGA scaffolds alone. In addition, AF cells showed the stronger production of GAG and collagen in HA/PLGA. Our results indicate that the HA/PLGA scaffold might be useful for intervertebral disc regeneration. Open image in new window

Transarterial chemoembolization (TACE) is the current standard of therapy for patients with intermediate-stage hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE (cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drug-eluting beads (DEBs) have been imposed as novel drug-delivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEB-TACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.

Poly(lactide-co-glycolic acid) (PLGA) has been widely used in the drug delivery and tissue engineering applications because of its good mechanical strength and biodegradation profile. However, cell attachment to the scaffold is low compared with that on fibrin although cells can be attached to the polymer surface. In this study, PLGA scaffolds were soaked in cells-fibrin suspension and polymerized with dropping fibrinogen-thrombin solution. Cellular proliferation activity was observed in PLGA/fibrin-seeded costal cartilage cells (CC) on 1, 3, and 7 days using the MTT assay and SEM. The effects of fibrin on the extracellular matrix (ECM) formation were evaluated using CC cell-seeded PLGA/ fibrin scaffolds. The PLGA/fibrin scaffolds elicited more production of glycosaminoglycan (GAG) and collagen than the PLGA scaffold. In this study, fibrin incorporated PLGA scaffolds were prepared to evaluate the effects of fibrin on the cell attachment and proliferation in vitro and in vivo. In this result, we confirmed that proliferation of cells in PLGA/fibrin scaffolds were better than in PLGA scaffolds. The PLGA/fibrin scaffolds provide suitable environment for growth and proliferation of costal cartilage cells.