Designing double-layered nanofibrous membranes as a wound dressing material

New generation wound dressings require the criteria that both bioactive and conventional wound dressing materials can recompense the fundamental properties like defense of wound from microbial invasion, dehydration during the wound care duration and mimic the healing process. In this study, functional double-layered nanofibrous composite membranes were fabricated via electrospinning method. The matrices consist of a sheet of ampicillin loaded poly(2-hydroxylethyl methacrylate/polyacrylic acid (pHEMA/pAA) nanofibers on the upper side (first layer: pH sensitive antibacterial barrier) and a sheet of poly(ε-caprolactone) (PCL)/gelatin nanofibers (second layer: bioactive part). Ampicillin was successfully incorporated to double-layered matrices which greatly changed the mechanical properties, biodegradability and water uptake ratios (up to 4 fold higher values). The success of the antimicrobial activity of ampicillin on Staphylococcus aureus and Escherichia coli was indicated by the inhibition zone test. pH sensitivity was confirmed by the swelling and ampicillin release studies by shifting pH value to basic environment. Thus, double-layered pHEMA-pAA nanofibers suggest as a potential wound dressing material for its pH sensitive drug delivery ability and its bioactive part.     

Preparation and Properties of Nylon 4/6 Copolymer Nanofibers Containing Silver-Zeolite Nanoparticles

Nylon 4/6 copolymer has desirable properties, such as high affinity to water and good tensile strength. These properties originate from the characteristics of nylon 4 and nylon 6. Zeolite is a good adsorptive material that has many pores in its structure and the ability to capture metallic ions. As a multifunctional additive, silver-ion-loaded zeolite nanoparticles were used to increase the moisture regain and impart antimicrobial properties to the nylon 4/6 copolymer. A nylon 4/6 nanofiber web was prepared by electrospinning from a polymer solution containing silver zeolite nanoparticles. The moisture regain of the nylon 4/6 nanofiber web increased with increasing amount of silver zeolite added. The web showed excellent antimicrobial activity against Klebsiella pneumoniae and Staphylococcus aureus. Overall, the nylon 4/6 nanofiber web could be a good material for wound healing dressings and high functional medical filters.     

Influence of Poly(lactic acid) Layer on the Physical and Antibacterial Properties of Dry Bacterial Cellulose Sheet for Potential Acute Wound Healing Materials

Dry bacterial cellulose nanofiber (BC) sheet coated with poly(lactic acid) (PLA) was developed and characterized towards acute wound healing applications. This new approach of PLA coating on BC revealed enhanced physical and antibacterial properties. Commercial BC sheets originated from the manufacturing of nata de coco jelly were dried and coated with the PLA at various concentrations of 2, 4, 6, 8, 10 and 12 % w/v for the purpose of improving the mechanical properties and followed by loading of antiseptic such as benzalkonium chloride (BAC). PLA has been proposed for the use of coating materials at a concentration of 8 %, the biocomposite sheet started exhibiting a low moisture uptake, prolonged swelling in simulated wound fluid solution and high tear (9.17 Nm²/kg) and burst indices (32.5 kPa·m²/g). The 8 % PLA coating revealed porous fiber-like morphology as observed under scanning electron microscope. Therapeutic loading capacity of the BC/8 PLA was substantially higher than the pristine BC. Furthermore strong antimicrobial activities against Staphylococcus aureaus and Escherichia coli were observed for the BC/8PLA biocomposite film. These reports were clearly suggestive of the fact that synthetic biodegradable polymers, such as PLA, may be exploited for the synergistic combination with BC for antimicrobial and acute wound management. This new and modified fiber source material could reduce the dependency on plant based cellulose for more demanding biomedical applications such as wound healing materials, vascular graft, cartilage replacement, drug delivery and tissue engineering.     

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

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

Antimicrobial and cellular activity of poly(L-lactide)/chitosan/Imipenem antibiotic composite nanofibers

Synthesis of biocompatible polymer nanofibers is valuable, due to their use as a cover for burns and as a replacement for bandage because of their antimicrobial properties. In this study, electrospinning of chitosan(Ch) and nanofibers synthesis with antibacterial properties was investigated. Nanofibers with antibacterial properties were synthesized by electrospun of Ch/poly(L-lactide)(PLA)/Imipenem(Imi) polymer solution. The results showed that the optimized ratio of Ch/PLA polymer solution was ratio of 50:50 and Ch 2 wt% and PLA 10 wt% polymer solution was the best weight percentage for nanofiber preparation. Also, the average diameter of Ch/PLA/Imi nanofibers was 143 nm and measured with ImageJ software. Afterwards, the antibacterial properties of Imi as additives (with different percentages) was studied in the polymer solution. The scanning electron microscopy (SEM) images and antibacterial tests were showed that the electrospun of Ch/PLA/Imi polymeric nanofibers were effective against Gram negative bacteria Escherichia coli (E. coli) and inhibited growth of E. coli. The growth and viability percentage of fibroblast cells with nanofibers in αMEM culture are at desirable levels after 6 days.     

Porous Laponite/Poly(L-lactic acid) Membrane with Controlled Release of TCH and Efficient Antibacterial Performance

Fabrication of porous polymer membrane with controlled drug release and efficient antibacterial performances is of great interest in biomedical fields. In this study, Laponite (LAP) nanodisks were first used to encapsulate a model antibiotic drug, tetracycline hydrochloride (TCH). Then, drug-loaded LAP nanodisks with an optimized loading efficiency (85.3 %) were mixed with poly(L-lactic acid) (PLLA) polymer to form drug-loaded composite porous membrane via solvent coasting. The structure, morphology and swelling property of the porous membranes formed with varied solvent ratio of methylene dichloride (DCM) and dimethyl formamide (DMF) in the mixture solvent were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy and swelling test. In vitro drug release behavior, the cytotoxicity and the antibacterial activity of drug-loaded composite membranes were evaluated. Results showed that the TCH release was dependent on the physical structure of PLLA membrane and the presence of LAP nanodisks effectively weakened the initial burst release of TCH, and improved the sustained release property of porous PLLA membrane. The released TCH of TCH/LAP/PLLA_3:1 and TCH/LAP/PLLA_4:1 was 10.0 % and 5.3 % within initial 1 h, respectively. More importantly, the porous TCH/LAP/PLLA membrane was cytocompatible and displayed considerable antibacterial activity, solely associated with the loaded TCH drug, confirming its potential utility in wound dressings and tissue engineering.     

Solution blowing of chitosan/PLA/PEG hydrogel nanofibers for wound dressing

In this study, a kind of hydrogel nanofibers were successfully fabricated via solution blowing of chitosan (CS) and polylactic acid (PLA) solutions mixed with various contents of polyethylene glycol (PEG) to offer hydration. The nanofibers with PEG content varying were average 341-376 nm in diameter with smooth surface and distributed randomly forming three-dimension (3D) mats. Glutaraldehyde (GA) vapor was then applied to impart stability, and the cross-linking reaction mainly occurred between GA and hydroxyl groups which was confirmed by XPS. The hydrogel nanofibers showed quick absorption behavior, high equilibrate water absorption and good air permeability which could help the mats absorbing excess exudates, creating a moist wound healing environment and oxygen exchanging in wound healing. The mats also exhibited good antibacterial activities against E. coil. The combination advantages of nanofibers mats and hydrogel will help it find promising application in wound healing.     

Investigation on the Biodegradability and Antibacterial Properties of Nanohybrid Suture Based on Silver Incorporated PGA-PLGA Nanofibers

Polyglycolic acid-poly lactic glycolic acid (PGA-PLGA) electrospun nanofibers containing silver nanoparticles have been produced and twisted into the nanofibrous yarn. The morphology of nanofibers and produced yarns, as well as the mechanical properties of the yarns, were investigated. Furthermore, in vitro antibacterial properties and in vitro degradation behavior of yarns containing various silver nanoparticles were studied. SEM images confirmed that the addition of the silver nanoparticles into the polymer solution increases the fiber diameters. The result of the mechanical test of the yarns alone and used in two different forms of the knots was measured and results showed that the strength of the yarns without the knot was significantly more than that of others. The biodegradability test showed that the mechanical properties and the weight of the yarns were quickly reduced after subjecting to in vitro condition. The result of the antibacterial test indicated that the nanofiber yarns containing %3 silver nanoparticles were the most appropriate sample with a considerably antibacterial activity against both gram-positive bacterium Staphylococcus aureus and gram-negative bacterium Escherichia Coli with inhibition zones of 8.1 and 9.5 mm, respectively; which demonstrated that silver nanoparticles retained their effectiveness after the electrospinning process. Therefore the nanofibrous yarns containing silver nanoparticles could be successfully produced by the electrospinning process with the proper antibacterial property as a candidate for the surgical sutures.     

Durable antibacterial cotton fabrics with chitosan based quaternary ammonium salt

A water soluble quaternary ammonium chitosan derivative, N-benzyl-N,N-diethyl chitosan quaternary ammonium salt (BDCQA), was prepared for antibacterial finish of cotton textiles. The effects of concentrations of finish agents and treatment time on the add-on ratio of cotton treated BDCQA (BDCQA-cotton) were studied in details. The morphology and thermal property of BDCQA-cotton were characterized by scanning electron microscopy (SEM) and thermagravimetric (TG) analysis. Gram-positive bacterium Staphylococcus aureus (S. aureus) and Bacillus cereus (B. cereus), Gram-negative bacterium Escherichia coli (E. coli) and drug-resistant bacterium Methicillin-resistant Staphylococcus aureus (MRSA), were used to evaluate the antibacterial activity and durability of BDCQA-cotton. The results showed that BDCQA-cotton possessed good antibacterial activity and high durability against broad spectrum bacterium. The preliminary investigation on the antibacterial mechanism was discussed in this work.     

Extraction,Dyeing, and Antibacterial Properties of <Emphasis Type="Italic">Crataegus Elbursensis</Emphasis> Fruit Natural Dye on Wool Yarn

Fruits obtained from shrubs of the Crataegus elbursensis (C. elbursensis) plant demonstrate significant antioxidant and antibacterial properties. In this study, natural dye was sono-extracted from fresh and dried fruits and applied in dyeing and antibacterial finishing of wool. The maximum sono-extraction yield was obtained when optimal conditions of ethanol/ water (4/1 v/v) as extracting solvent, time 30 min, pH 4, temperature 50 oC, and C. elbursensis concentration 10 g/l were used. When wool yarns were dyed with the extracted natural dye, the maximum dye uptake was achieved using dye concentration 75 % owf, and dyeing condition of 100 oC, 60 min, pH 4, and LR 100:1. Different metal salts like aluminum sulfate, copper sulfate, and tin chloride were applied on wool by pre-mordanting method and their effects on dye uptake, color variation, and color fastness were examined. Results showed that the natural dye itself had relatively high uptake and good color fastness on un-mordanted wool. Further, each mordant had different effect on dye uptake, color variation, and color fastness properties depending on its coordination ability with dye molecules and wool chains. Moreover, dyed yarns showed good antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria.     

Tuning the properties of PVDF or PVDF-HFP fibrous materials decorated with ZnO nanoparticles by applying electrospinning alone or in conjunction with electrospraying

Novel composite nanofibrous materials of poly(vinylidene fluoride) (PVDF) or poly(vinylidene fluoride-cohexafluoropropylene) (PVDF-HFP) and ZnO nanoparticles were prepared by conjunction of electrospinning and electrospraying techniques. Simultaneous electrospinning of concentrated solution of PVDF or PVDF-HFP and electrospraying of suspension of ZnO in diluted PVDF or PVDF-HFP solution enable the preparation of materials consisting of fibers on which ZnO was deposited on the fibers’ surface (design type “on”). These fibrous materials were compared with materials consisting of PVDF or PVDF-HFP fibers in which ZnO was incorporated in the fibers (design type “in”) and which were obtained by one-pot electrospinning of a suspension of ZnO nanoparticles in concentrated PVDF or PVDF-HFP solution. The fiber morphology and the presence of ZnO “in” or “on” the fibers were observed by scanning electron microscopy (SEM) and by transmission electron microscopy (TEM). The effect of the used technique on the type, size and shape of the obtained structures was discussed. The fibrous mats were studied by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), contact angle measurements and mechanical tests as well. It was found that the decoration of fibers with ZnO resulted in increase of their thermal stability and hydrophobicity. The microbiological tests showed that the materials of design type “on” possessed strong antibacterial activity against the pathogenic microorganism Staphylococcus aureus. The results suggest that, due to their antibacterial activity, the obtained composite materials are suitable for wound dressing applications.     

Fabrication,Characterization and Antimicrobial property of natural TTOLs/CS composite sponges

The essential oil liposomes, a kind of ecological friendly natural antibacterial agents, have good bactericidal effect. In the present study, tea tree oil liposomes (TTOLs) were prepared by the thin-membrane hydration method with sonication, and then were blended with chitosan (CS) to successfully fabricate novel TTOLs/CS composite sponges by freeze-dried method. Through the scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR) and performance tests, it was found that the material had good water absorption, water retention and water vapor permeability due to the high porosity. Furthermore, the incorporation of TTOLs in the CS-based sponges significantly improved the microbicidel effect of the sponges against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Candida albicans (C. albicans). Killing log values of TTOLs/CS composite sponges against bacteria and fungi reached over 3. According to the microbial clearance test, propidium iodide (PI) fluorescence test and transmission electron microscope (TEM) observation, the results indicated on one hand that TTOLs/CS composite sponges adsorbed and intercepted microbial cells through the internal pore and surface charge, and on the other hand that they could destroy bacterial intercellular substance, disperse cell colony and damage the integrity of cell membrane, finally leading to the death of microbial cells. In summary, TTOLs/CS composite sponges had great potential to be used as antimicrobial materials in the field of food, cosmetics, medicine, biomedical and biochemical engineering.     

Antibacterial Coating of Glass Fiber Filters with Silver Nanoparticles (AgNPs) and Glycidyltrimethylammonium Chloride (GTAC)

Silver nanoparticles (AgNPs) were attached to glass fiber filters to improve their antibacterial properties using glycidyltrimethylammonium chloride (GTAC), a type of quaternary ammonium salt. The glass fiber filters treated with GTAC were placed into the Ag colloid and heat-treated at 43 °C for 90 min to attach AgNPs to the glass fiber filters. The glass fiber filters with the attached AgNPs were then analyzed by scanning electron microscopy and atomic force microscopy (AFM). The surface morphology of the glass fiber filters treated with GTAC and AgNPs was observed. The Ag atomic % of the glass fiber filters was analyzed according to the GTAC concentration, Ag colloid concentration, and AgNPs treatment temperature. The surface roughness of the glass fiber filters with the attached AgNPs was measured by AFM. The antibacterial tests of the GTAC and AgNP-treated glass fiber filters highlighted the sufficient antibacterial effects against E. coli, S. aureus, and P. aeruginosa. In particular, the antibacterial properties of glass fiber filters against S. aureus and P. aeruginosa were improved when the glass fiber filters were treated with both GTAC and AgNPs.     

Thermo-Mechanical Characterization of a Thermoplastic Copolyetherester (TPC): Experimental Investigation

In this article, the thermo-mechanical characterization of poly(butylene terephthalate)/poly(tetramethylene oxide) (PBT/PTMO) is studied by thermal analysis, dynamic mechanical analysis, and uniaxial tensile tests. The results of poly(ether esters) show that the melting temperature is equal to T _m =193 °C, which is 31 °C, lower than that of the melting temperature of poly(butylene terephthalate) (PBT). Its glass transition temperature, T _g is equal to -61 °C, determined by DMA. The melting and cooling temperatures (T _m , T _c ) after aging at T₀+48 h and T₀+week are virtually unchanged. Moreover, the results of the tensile tests show that the effect of the low deformation rate reduces the friction resulting from the sliding mechanisms between the amorphous and crystalline parts.     

One Step Thermochromic Pigment Printing and Ag NPs Antibacterial Functional Finishing of Cotton and Cotton/PET Fabrics

One step thermochromic pigment printing and antibacterial functionality of cotton (100 %) and cotton/polyester blend (50/50 %) were demonstrated in this study. The improvement in antimicrobial activity against G+ve (Bacillus cereus) and G-ve (E. coli), and pigment printability were achieved by inclusion of Ag-NPs (30 g/kg) into pigment printing paste followed by printing and microwave curing at 700 W for 5 min. Modes of interactions were proposed, and surface modification was also confirmed by SEM and EDX analysis that proved the presence of Ag-NPs in cotton and cotton/ polyester blended samples. The results indicated that the colour fastness to wash and rubbing was excellent, the surface roughness reduced, and exhibited good antibacterial activity against Bacillus cereus and E. coli bacteria.     

Dyeability and Antibacterial Finishing of Hemp Fabric Using Natural Bioactive Neem Extract

Two functional compounds were successfully extracted from neem (Azadiracta indica): a tannin-rich natural dye and an antibacterial agent. The dye was extracted from the bark using water, and the antibacterial from the leaf using methanol. These were used to dye hemp fabrics. Higher color strength values (K/S) were found when dyeing was conducted at a higher dye concentration, elevated temperature, and longer dyeing time. Optimal results were achieved when using 5 %w/v of extracted powder at 100 °C for 60 min. The resulting fabrics appeared reddish-brown, and were rated as good to excellent for color fastness against washing, water, sea water, and perspiration. The antibacterial agent from the neem leaf was extracted by Soxhlet apparatus at 65 °C with methanol as solvent. The dyed and antibacterial-finished hemp fabrics were tested against Staphylococcus aureus, following the percentage reduction test of AATCC 100. The treated fabrics demonstrated a 99.99 % reduction in Staphylococcus aureus.     

Application of MCT-βCD to Modify Cellulose/Wool Blended Fabrics for Upgrading Their Reactive Printability and Antibacterial Functionality

Pre-loading of monochlorotriazinyl β-Cyclodextrin (MCT-βCD) onto/within viscose/wool (V/W) and cotton/wool (C/W) blended fabrics provide hosting cavities that can form host-guest inclusion complexes with reactive dyes in postprinting as well as with triclosan derivative or silver nanoparticles/hyperbranched polyamide-amine (AgNPs/HBPAA) composite in subsequent final antibacterial finishing step. Coloration properties, antibacterial activity against (S. aureus) and (E. coli) pathogenic bacteria, durability of the obtained products, according to the above mentioned route, to wash, surface morphology and composition of selected samples were investigated. Results obtained signify that premodification of the nominated substrates with MCT-βCD (10 g/l), followed by reactive printing with mono-or bifunctional reactive dye (20 g/l), and subsequent post-finishing with triclosan derivative or AgNPs/HBPAA composite (15 g/l each) is an efficient treatments sequence for attaining reactive prints with significant antibacterial efficacy and noticeable durability to wash. Surface depositions of selected active ingredients were also confirmed using SEM and EDX analysis.     

Eco-friendly and Durable Antibacterial Cotton Fabrics Prepared with Polysulfopropylbetaine

A novel antibacterial agent polysulfopropylbetaine (PSPB) bearing carboxyl groups was synthesized and its application on cotton fabric to provide durable antibacterial property was also presented. The successful synthesis of PSPB and its immobilization onto the cotton fabric surface were verified by a series of tests including FTIR, ¹H NMR, XPS and SEM. Viable cell counting method was employed to investigate antibacterial properties of the finished cotton fabrics. It was found that the cotton fabrics treated with PSPB were endowed with desirable antibacterial activity against both gram-negative bacteria Esherichia coli (E.coli, AATCC 6538) and gram-positive bacteria Staphylococcus aureus (S.aureus, AATCC 25922), with the bacterisotatic rates of 99.69 % and 99.95 %, respectively. Notably, the bacterial reduction rates still maintained over 90 % against both bacteria even after 50 consecutive laundering cycles. Moreover, tests concerning the hydrophilicity, air permeability, water vapor transmission, mechanical properties as well as thermal properties were carried out systematically. The experimental results indicated the hydrophilic performance, air permeability and moisture penetrability of the cotton fabrics finished with PSPB were improved greatly in spite of a slight reduction in thermal performance and little obvious influence on mechanical performance. The antibacterial cotton fabric has the potential to be applied in sportswear, underwear, household textiles, medical fields and much more.     

Study on antibacterial and comfort performances of cotton fabric finished by chitosan-silver for intimate apparel

The fabric used for intimate apparel is widely required to have excellent antibacterial and comfort performances. In order to improve its antibacterial ability, this paper studied chitosan-silver finishing on the cotton knitted fabric. The study indicates that the chitosan-silver attached to the fabric exhibits excellent antibacterial action against the typical bacteria of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureu). The anti-bacterial mechanism of chitosan-silver against E. coli and S. aureu were investigated. To guarantee its prominent comfort performance, measurements were made on the finished fabric of its air permeability, water vapor transmission, hydrophily, surface friction and bending ability against the control fabric, which is currently used for intimate apparel. The antibacterial and comfort performances were compared between the tested fabrics. The results show that the air permeability and the hydrophily of the finished cotton fabric are significantly better than the control one, while the water vapor transmission, the surface friction and the adjustable rate remain similar to each other. The bending rigidity of the finished fabric is slightly better due to the attachment of chitosan within accepted threshold. The dual compounding theory of chitosan-silver proves to be useful for a higher synergistic effect of anti-bacteria, lower whiteness degradation and overall optimization of comfort performance. This dual compounding theory of chitosan-silver is valuable for improving antibacterial and comfort performances of intimate apparel.     

Antibacterial mechanism of polyacrylonitrile fiber with organophosphorus groups against <Emphasis Type="Italic">Escherichia coli</Emphasis>

A series of novel polyacrylonitrile fibers (PANF) with organophosphorus groups (OPh-PANF) showing unique antibacterial activities were synthesized in our previous studies. To understand the antibacterial mechanism of OPh-PANF, E. coli was selected as the model of Gram-negative bacteria and a list of biological experiments were conducted and analyzed in the current study. Results from scanning electron microscope (SEM), transmission electron microscope (TEM) and flow cytometry (FCM) analyses showed that the integrity of the cell membrane was severely damaged, causing a large number of intracellular potassium ions and macromolecular proteins leaking out of the cells. In addition, OPh-PANF can disrupt the intracellular enzyme systems by FCM analysis. Results from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry (MS) analyses showed that after exposure to OPh-PANF, specific protein bands disappeared or weakened, indicating that OPh-PANF mainly inhibited synthesis and expression of structural proteins (OmpA) and functional proteins (HtpG, AhpC, FNM, CAD). On the basis of the above results, an antibacterial mechanism was proposed for OPh-PANF against E. coli. When OPh-PANF was exposed to E. coli, the first step was to adsorb E. coli on its surface, then organophosphorus groups pre-grafted on the fibers began to execute the function of killing bacteria through three combined ways, i.e. destruction of cell membrane structure, disordering of enzyme system and inhibition of protein synthesis.