Biocompatibility and sub-chronic toxicity studies of phlorotannin/polycaprolactone coated trachea tube for advancing medical device applications.

The phlorotannin-polycaprolactone-coated endotracheal tube (PP tube) has been developed with the aim of preventing tracheal stenosis that can result from endotracheal intubation, a factor that can lead to a serious airway obstruction. Its preventive efficacy has been assessed through both in vitro and in vivo investigations. However, there is a lack of studies concerning its biocompatibility and sub-chronic toxicity in animal models, a crucial factor to ensure the safety of its usage as a functional endotracheal tube. Thus, this study aimed to evaluate the biocompatibility and sub-chronic (13 weeks) toxicity of the PP tube through L929 cell line and diverse in vivo models. The cytotoxicity testing was performed using the extracts of PP tube on L929 cells for 72 h. Furthermore, other tests conducted on animal models, including ICR mice (acute systemic toxicity), New Zealand white rabbit (intradermal reactivity and pyrogen tests), guinea pig (maximization sensitization), and Sprague Dawley rats (sub-chronic toxicity). In both biocompatibility and sub-chronic toxicity analyses, no significant adverse effects are observed in the groups exposed to the PP tube, when compared to control group. Altogether, the findings suggested that the PP tube exhibits relative non-toxic and safety, supporting its suitability for clinical usage. However, extended periods of intubation may produce mild irritant responses, highlighting the clinical caution of limiting intubation duration to less than 13 weeks.

Brown Algae Dictyopteris divaricata Attenuates Adipogenesis by Modulating Adipocyte Differentiation and Promoting Lipolysis through Heme Oxygenase-1 Activation in 3T3-L1 Cells.

The present study aims to explore the probable anti-adipogenesis effect of Dictyopteris divaricata (D. divaricata) in 3T3-L1 preadipocytes by regulating heme oxygenase-1 (HO-1). The extract of D. divaricata retarded lipid accretion and decreased triglyceride (TG) content in 3T3-L1 adipocytes but increased free glycerol levels. Treatment with the extract inhibited lipogenesis by inhibiting protein expressions of fatty acid synthase (FAS) and lipoprotein lipase (LPL), whereas lipolysis increased by activating phosphorylation of hormone-sensitive lipase (p-HSL) and AMP-activated protein kinase (p-AMPK). The extract inhibited adipocyte differentiation of 3T3-L1 preadipocytes through down-regulating adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1). This is attributed to the triggering of Wnt/ß-catenin signaling. In addition, this study found that treatment with the extract activated HO-1 expression. Pharmacological approaches revealed that treatment with Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, resulted in an increase in lipid accumulation and a decrease in free glycerol levels. Finally, three adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP1, restored their expression in the presence of ZnPP. Analysis of chemical constituents revealed that the extract of D. divaricata is rich in 1,4-benzenediol, 7-tetradecenal, fucosterol, and n-hexadecanoic acid, which are known to have multiple pharmacological properties.

Poly(vinyl alcohol)/chitosan hydrogel incorporating chitooligosaccharide-gentisic acid conjugate with antioxidant and antibacterial properties as a potential wound dressing.

The design and development of wound dressing with antioxidant and antibacterial properties to accelerate wound healing remain challenging. In this study, we synthesize a chitooligosaccharide-gentisic acid (COS-GSA) conjugate using the free-radical grafting method, and fabricate a poly(vinyl alcohol) (PVA)/chitosan (CH)/COS-GSA (PVA/CH/CG) hydrogel using a freeze-thaw method. We characterize the synthesized COS-GSA conjugates using through polyphenol assay, absorbance, and 1H NMR spectroscopy and evaluate their antioxidant properties. The COS-GSA conjugates are successfully synthesized and exhibit better antioxidant properties than pristine COSs. Subsequently, the fabricated hydrogel is characterized based on its morphological analysis, rheological properties, water contact angle, swelling, degradation, water retention properties, and COS-GSA release profiles. Finally, the biocompatibility of the fabricated hydrogel is evaluated on HDF and HaCaT cells through indirect and direct cytotoxicity. The PVA/CH/CG hydrogel exhibited significantly higher antioxidant properties (DPPH, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydrogen peroxide (H2O2) scavenging activities) and antibacterial activities (Staphylococcus aureus and Pseudomonas aeruginosa) compared to other fabricated hydrogels such as PVA, PVA/CH, and PVA/CH/COS (PVA/CH/C). These results provide evidence that PVA/CH/CG hydrogels with antioxidant, antibacterial, and non-cytotoxic properties have great potential for wound-dressing applications.

Chemical constituents of the culture broth of Dentipellis fragilis and their anti-inflammatory activities.

Seven undescribed compounds, dentipellinones A‒D (1, 2, 5, and 6), dentipellinol (3), methoxyerinaceolactone B (4), and erinaceolactomer A (7), were isolated from the culture broth of Dentipellis fragilis. Chemical structures of these isolated compounds were determined by analyses of 1D and 2D-NMR and MS data in comparison with data reported in the literature. Absolute configurations of 1‒7 were also determined by Electronic Circular Dichroism calculations. The isolated compounds were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokines levels in LPS-stimulated RAW264.7 cells. Compounds 5 and 7 were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokine levels in LPS-stimulated RAW264.7 cells. They exhibited inhibitory effects on LPS-induced NO production in a dose-dependent manner, and significantly reduced the levels of inflammatory-related cytokines such as IL-1ß and IL-6. TNF-α was not involved in the anti-inflammatory effects of these compounds. Finally, compounds 5 and 7 showed significant anti-inflammatory effects.

Angiotensin I-Converting Enzyme (ACE) Inhibition and Molecular Docking Study of Meroterpenoids Isolated from Brown Alga, Sargassum macrocarpum.

Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids isolated from the brown alga, Sargassum macrocarpum, and the molecular mechanisms underlying ACE inhibition. Four fractions of S. macrocarpum were prepared using hexane, chloroform, ethyl acetate, and water as solvents and analyzed for their potential ACE-inhibitory effects. The chloroform fraction showed the strongest ACE-inhibitory effect, with an IC50 value of 0.18 mg/mL. Three meroterpenoids, sargachromenol, 7-methyl sargachromenol, and sargaquinoic acid, were isolated from the chloroform fraction. Meroterpenoids isolated from S. macrocarpum had IC50 values of 0.44, 0.37, and 0.14 mM. The molecular docking study revealed that the ACE-inhibitory effect of the isolated meroterpenoids was mainly attributed to Zn-ion, hydrogen bonds, pi-anion, and pi-alkyl interactions between the meroterpenoids and ACE. These results suggest that S. macrocarpum could be a potential raw material for manufacturing antihypertensive nutraceutical ingredients.

Isolation and Characterization of Efficient Active Compounds Using High-Performance Centrifugal Partition Chromatography (CPC) from Anti-Inflammatory Activity Fraction of Ecklonia maxima in South Africa.

Ecklonia maxima is a brown seaweed, which is abundantly distributed in South Africa. This study investigated an efficient approach using high-performance centrifugal partition chromatography (HPCPC), which has been successfully developed for the isolation and purification of phlorotannins, eckmaxol, and dieckol from the ethyl acetate fraction of E. maxima (EEM). We evaluated EEM for its inhibitory effect against lipopolysaccharide (LPS)-induced inflammatory responses in zebrafish embryos. The separation of eckmaxol and dieckol from samples of EEM using HPCPC was found to be of high purity and yield under an optimal solvent system composed of n-hexane:ethyl acetate:methanol:water (2:7:3:7, v/v/v/v). To evaluate the anti-inflammatory efficacy of EEM containing active compounds, zebrafish embryos exposed to LPS were compared with and without EEM treatment for nitric oxide (NO) production, reactive oxygen species (ROS) generation, and cell death two days after fertilization. These evaluations indicate that EEM alleviated inflammation by inhibiting cell death, ROS, and NO generation induced by LPS treatment. According to these results, eckmaxol and dieckol isolated from brown seaweed E. maxima could be considered effective anti-inflammatory agents as pharmaceutical and functional food ingredients.

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.

Antihypertensive Effects of IGTGIPGIW Peptide Purified from Hippocampus abdominalis: p-eNOS and p-AKT Stimulation in EA.hy926 Cells and Lowering of Blood Pressure in SHR Model.

The aim of this study was to assess the potential hypertensive effects of the IGTGIPGIW peptide purified from Hippocampus abdominalis alcalase hydrolysate (HA) for application in the functional food industry. We investigated the antihypertensive effects of IGTGIPGIW in vitro by assessing nitric oxide production in EA.hy926 endothelial cells, which is a major factor affecting vasorelaxation. The potential vasorelaxation effect was evaluated using 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, a fluorescent stain. IGTGIPGIW significantly increased the expression of endothelial-derived relaxing factors, including endothelial nitric oxide synthase and protein kinase B, in EA.hy926 cells. Furthermore, oral administration of IGTGIPGIW significantly lowered the systolic blood pressure (183.60 ± 1.34 mmHg) and rapidly recovered the diastolic blood pressure (143.50 ± 5.55 mmHg) in the spontaneously hypertensive rat model in vivo. Our results demonstrate the antihypertensive activity of the IGTGIPGIW peptide purified from H. abdominalis and indicate its suitability for application in the functional food industry.

Fucoidan Isolated from Sargassum confusum Suppresses Inflammatory Responses and Oxidative Stress in TNF-α/IFN-γ- Stimulated HaCaT Keratinocytes by Activating Nrf2/HO-1 Signaling Pathway.

Recent studies have revealed that marine brown seaweeds contain numerous bioactive compounds which exhibit various bioactivities. The present study investigated the effect of low molecular weight fucoidan (SCF) isolated from Sargassum confusum, a brown alga, on inflammatory responses and oxidative stress in HaCaT keratinocytes stimulated by tumor necrosis factor (TNF)-α/interferon (IFN)-γ. SCF significantly increased the cell viability while decreasing the intracellular reactive oxygen species (ROS) production in TNF-α/IFN-γ-stimulated HaCaT keratinocytes. In addition, SCF effectively reduced inflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-8, IL-13, TNF-α, and IFN-γ) and chemokines (Eotaxin, macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)) expression, by down-regulating the expression of epithelial and epidermal innate cytokines (IL-25, IL-33, and thymic stromal lymphopoietin (TSLP)). Furthermore, SCF suppressed the activation of TNF-α/IFN-γ-stimulated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, while activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. The cytoprotective effect of SCF against TNF-α/IFN-γ stimulation was considerably reduced upon inhibition of HO-1 activity by ZnPP. Overall, these results suggest that SCF effectively suppressed inflammatory responses and oxidative stress in TNF-α/IFN-γ-stimulated HaCaT keratinocytes via activating the Nrf2/HO-1 signaling pathway.

A phlorotannins-loaded homogeneous acellular matrix film modulates post-implantation inflammatory responses.

Peritendinous adhesion mainly occurs between proliferating fibrous tissues and adjacent normal organs after surgery. Many physical barriers are applied to the implanted site to prevent peritendinous adhesion. However, these barriers often trigger inflammatory responses. Therefore, our study sought to develop phlorotannins-loaded cartilage acellular matrix (CAM) films as a physical barrier and investigate their inhibitory effect on inflammatory responses, which are associated with the induction of postoperative peritendinous adhesion (PAA). Our findings indicated that incorporating phlorotannin into the CAM film did not affect its unique characteristics including its thermal and spectroscopic properties. Moreover, the phlorotannins-loaded CAM films suppressed the expression of inflammatory mediators on RAW 264.7 macrophages stimulated using Escherichia coli lipopolysaccharides and exhibited an anti-inflammatory effect when implanted subcutaneously in rats. Therefore, our results highlight the potential of phlorotannins-loaded CAM films as a promising physical barrier to prevent PAA.

Anti-Allergic Effect of Low Molecular Weight Digest from Abalone Viscera on Atopic Dermatitis-Induced NC/Nga.

Abalone viscera (AV) is one of the byproducts of the seafood processing industry. The low molecular weight (<5 kDa) peptides (LMW-AV) obtained from gastrointestinal digestion of AV could suppress allergenic responses on activated HMC-1 human mast cells in our previous study. Regarding the allergenic response of LMW-AV, in the present study, we further investigated the potential of oral administration of LMW-AV against atopic dermatitis (AD) in a dermatitis-induced model stimulated with Dermatophagoides farinae. The results demonstrated that the LMW-AV reduced a number of clinical symptoms, such as the severity of the dermatitis and serum immunoglobulin E levels. Moreover, LMW-AV could inhibit the expression of chemokines and cytokines. The histological analysis indicated that the LMW-AV has suppressed the eosinophil count and the mast cell infiltration into the upper dermis. The results suggest that LMW-AV can be considered as a promising candidate for AD treatment.

Wound healing properties of triple cross-linked poly (vinyl alcohol)/methacrylate kappa-carrageenan/chitooligosaccharide hydrogel.

To develop an effective and mechanically robust wound dressing, a poly (vinyl alcohol) (PVA)/methacrylate kappa-carrageenan (κ-CaMA) composite hydrogel encapsulated with a chitooligosaccharide (COS) was prepared in a cassette via repeated freeze/thaw cycles, photo-crosslinking, and chemical cross-linking. The chemical, physical, mechanical, in vitro biocompatibility, in vivo wound-healing properties, and antibacterial activity of triple-crosslinked hydrogel were subsequently characterized. The results showed that the PVA/κ-CaMA/COS (Pκ-CaC) hydrogel had a uniformly thick, highly porous three-dimensional architecture with uniformly distributed pores, a high fluid absorption, and retention capacity without disturbing its mechanical stability, and good in vitro biocompatibility. Macroscopic images from the full-thickness skin wound model revealed that the wounds dressed with the proposed Pκ-CaC hydrogel were completely healed by day 14, while the histomorphological results confirmed full re-epithelization and rapid skin-tissue remodeling. This study thus indicates that the composite Pκ-CaC hydrogel has significant potential for use as a wound dressing.

Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering.

Polydeoxyribonucleotides (PDRNs) are a family of DNA-derived drugs with a molecular weight ranging from 50 to 1500 kDa, which are mainly extracted from the sperm cells of salmon trout or chum salmon. Many pre-clinical and clinical studies have demonstrated the wound healing and anti-inflammatory properties of PDRN, which are mediated by the activation of adenosine A2A receptor and salvage pathways, in addition to promoting osteoblast activity, collagen synthesis, and angiogenesis. In fact, PDRN is already marketed due to its therapeutic properties against various wound healing- and inflammation-related diseases. Therefore, this review assessed the most recent trends in marine organism-derived PDRN using the Google Scholar search engine. Further, we summarized the current applications and pharmacological properties of PDRN to serve as a reference for the development of novel PDRN-based technologies.

Electrospun porous bilayer nano-fibrous fish collagen/PCL bio-composite scaffolds with covalently cross-linked chitooligosaccharides for full-thickness wound-healing applications.

The development of tissue-engineered biodegradable artificial tissue substitutes with extracellular matrix-mimicking properties that govern the interaction between the material and biological environment is of great interest in wound-healing applications. In the present study, novel bilayer nanofibrous scaffolds composed of fish collagen (FC) and poly(ε-caprolactone) (PCL) were fabricated using electrospinning, with the covalent attachment of chitooligosaccharides (COS) via carbodiimide chemistry. The architecture and fiber diameter of the non-cross-linked nanofibrous scaffolds remained consistent irrespective of the polymer ratio under different electrospinning conditions, but the fiber diameter changed after cross-linking in association with the FC content. Fourier-transform infrared spectroscopy analysis indicated that the blend of biomaterials was homogenous, with an increase in COS levels with increasing FC content in the nanofibrous scaffolds. Based on cytocompatibility analysis (i.e., the cellular response to the nanofibrous scaffolds and their interaction), the nanofibrous scaffolds with high FC content were functionally active in response to normal human dermal fibroblast­neonatal (NHDF-neo) and HaCaT keratinocyte cells, leading to the generation of a very effective tissue-engineered implant for full-thickness wound-healing applications. In addition to these empirical results, an assessment of the hydrophilicity, swelling, and mechanical integrity of the proposed COS-containing FC-rich FC/PCL (FCP) nanofibrous scaffolds confirmed that they have significant potential for use as tissue-engineered skin implants for rapid skin regeneration.

3D PCL/fish collagen composite scaffolds incorporating osteogenic abalone protein hydrolysates for bone regeneration application: in vitro and in vivo studies.

Three-dimensional (3 D) printing is an effective technology that has shown considerable potential for use in tissue regeneration. Of the many materials that have been proposed for this purpose, poly (ε-caprolactone) (PCL) 3 D scaffolds have been received significant attention in the bone tissue engineering field due to its advantageous mechanical properties and biocompatibility. In this study, a novel method was developed for tissue-engineered bone that combines PCL 3 D scaffolds with fish collagen (Col) and the osteogenic abalone intestine gastro-intestinal digests (AIGIDs) from Haliotis discus hannai. And then, mouse mesenchymal stem cells (MSCs) were seeded onto the fabricated scaffolds. After in vitro culturing, the proliferation of the MSCs on the scaffolds, alkaline phosphatase (ALP) activity, and the amount of deposited calcium were investigated. The results indicated that the ALP activity and mineralization in PCL/AIGIDs/Col was higher than that of the other scaffolds. In an in vivo experiment, the two fabricated scaffolds were implanted in a rabbit tibia. PCL/AIGIDs/Col group exhibited strong osteoinduction capability in the rabbit tibia defect model. These stimulated biological responses in vitro and in vivo suggest that the PCL/AIGIDs/Col scaffold are promising material for use in tissue implants and bone regeneration.

Characterization of an oxidized alginate-gelatin hydrogel incorporating a COS-salicylic acid conjugate for wound healing.

In the present study, chitooligosaccharide (COS) and salicylic acid (SA) conjugates were synthesized using H2O2-induced grafting polymerization and oxidized alginate (OA) and gelatin hydrogels were fabricated using Schiff's base reaction. To confirm the synthesis and improved activity of the COS-SA conjugates, polyphenol assays, ultraviolet absorbance, NMR, and antioxidant activity tests were all conducted. The results showed that the COS-SA conjugates were completely synthesized and improved antioxidant activity. OA was synthesized using a periodate method and a hydrogel was obtained at a mixed ratio of 3:7 via crosslinking between the aldehyde group of the OA and the amine groups of gelatin with COS-SA conjugates. In a cytotoxicity and wound healing model, the hydrogels with COS-SA conjugates did not exhibit cytotoxicity and exhibited wound healing activity in a mouse model. These results provide evidence that OA and gelatin hydrogels with a COS-SA conjugate can be successfully used for wound healing applications.

Antithrombin III-mediated blood coagulation inhibitory activity of chitosan sulfate derivatized with different functional groups.

Acylated chitosan sulfate (ChS1), a sulfated polysaccharide with high anticoagulant activity, was chemically synthesized and structurally characterized using FT-IR analysis. The beneficial structural properties and high availability of the sulfate group in ChS1 led to greater anticoagulant activity through both the intrinsic and common pathways with antithrombin III (AT III)-mediated inhibition, particularly involving coagulation factors FXa and FIIa. The analysis of the binding affinities using surface plasma resonance found that the equilibrium dissociation constant (KD) of ChS1 for FXa and FIIa in the presence of AT III was 67.4 nM and 112.6 nM, respectively, indicating the stronger interaction of the AT III/ChS1 complex with the ligands and the inhibition of activated FX and FII. The results of amidolytic assays further demonstrated the stronger inhibition of the proteolytic conversion of factor X by the intrinsic FXase complex and of FII by the prothrombinase complex. Molecular docking analysis further validated the protein-ligand interactions of ChS1 with AT III and their binding affinity.

Recent advances in biological macromolecule based tissue-engineered composite scaffolds for cardiac tissue regeneration applications.

Tissue engineering has become a primary research topic for the treatment of diseased or damaged cardiac tissue, which is a global healthcare concern. Current tissue engineering strategies utilise biomimetic scaffolds and cells that promote healthy growth and regeneration of cardiac tissue. Successful cardiac tissue engineering (CTE) requires scaffolds that mimic the natural anisotropy and microstructure of native tissues, while simultaneously supporting proliferation and differentiation and acting as a natural extracellular matrix (ECM) substitute until it is replaced by the body's residing cells. Among the various types of scaffolding materials, naturally occurred biological macromolecules, synthetic polymers, electroconductive polymers and electroconductive nanoparticles are utilised due to their unique biological and physicochemical properties. In this context, naturally occurred biological macromolecules has gained significant attention in designing tissue engineered composite scaffolds for cardiac tissue regeneration applications due to their excellent biocompatibility, cytocompatibility, biodegradability, and low immunogenicity. The objective of this review is to summarize the micro and macro architecture of the heart and its functional properties and provides a firm summarization of recent progress in biological macromolecules based composites scaffolds with innovative fabrication techniques so that it may help the design of novel substitutes for cardiac tissue regeneration application.

Characterization of ionic cross-linked composite foams with different blend ratios of alginate/pectin on the synergistic effects for wound dressing application.

Alginate and pectin have been widely employed together in various industrial and biomedical applications due to their synergistic interaction. Although alginate and pectin have been used as composite materials in films, gels, and particles, research characterizing their properties in foams is scarce. Thus, in the present study, we fabricated alginate-pectin composite foams with different blending ratios (9:1, 7:3, and 5:5) using calcium ion cross-linking and characterized their properties. It was found that the G' values of rehydrated alginate-pectin 9:1 foam was higher than those of the other rehydrated foams in the rheological behavior. In addition, higher pectin levels in the composite foams led to more water being absorbed during swelling tests and the higher release of BSA in drug-release testing. In indirect and direct cytotoxicity testing, none of the foams exhibited cell cytotoxicity for fibroblast and keratinocyte cells. These results suggest that controlling the pectin content in alginate-pectin foams is key to adjusting their mechanical properties, water absorption, and drug-release ability. In addition, alginate-pectin composite foams are promising candidates for use in wound-dressing applications.

Antimicrobial hydrogels based on PVA and diphlorethohydroxycarmalol (DPHC) derived from brown alga Ishige okamurae: An in vitro and in vivo study for wound dressing application.

In this study, we fabricated polyvinyl alcohol hydrogels containing diphlorethohydroxycarmalol (DPHC) from Ishige okamurae for its anti-bacterial effect in wound-dressing applications. First, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of DPHC against Staphylococcus aureus and Pseudomonas aeruginosa were investigated, and these were found to be about 128 µg/mL and 512 µg/mL, respectively. Polyvinyl alcohol hydrogels loaded with different concentrations of DPHC were then produced for the dressing of wounds to assist in the healing process and to provide an antibacterial effect. To investigate the characteristics of the proposed PVA/DPHC hydrogels, we conducted SEM analysis, rheological analysis, thermogravimetric analysis, water swelling analysis, drug release testing, and gel fraction assessment. The antibacterial activity of the PVA/DPHC hydrogels was also tested against the gram-positive bacterium S. aureus and the gram-negative bacterium P. aeruginosa using ASTM E2149 tests. The biocompatibility of the PVA/DPHC hydrogels was assessed using in vitro indirect and direct contact tests and in vivo tests on ICR mice. The PVA/DPHC hydrogels exhibited the ability to reduce the viability of S. aureus and P. aeruginosa by about 99% in ASTM E2149 testing, while not producing any toxic effect on NHDF-Neo or HaCaT cells as shown in MTT assays and in vitro FDA fluorescence analysis. In addition, the PVA/DPHC hydrogels had a strong wound healing effect when compared to non-treated groups of ICR mice in vivo. Based on the characterization of the PVA/DPHC hydrogels in vitro and in vivo, this study suggests that the proposed hydrogel has significant potential for use in wound dressing.