Biotechnology Advances 31 (2013) 421–437

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Research review paper

Electrospun cellulose acetate nanofibers: The present status and gamut ofbiotechnological applications

Rocktotpal Konwarh a,1, Niranjan Karak b,⁎, Manjusri Misra a,c

a Bioproducts Discovery and Development Centre, Department of Plant Agriculture, Crop Science Building, University of Guelph, ON, Canada N1G2W1b Advanced Polymers and Nanomaterials Laboratory, Department of Chemical Sciences, Tezpur University, Napaam, Sonitpur, Assam-784028, Indiac School of Engineering, Thornbrough Building, University of Guelph, ON, Canada N1G2W1

⁎ Corresponding author. Tel.: +91 3712 267009; fE-mail address: karakniranjan@yahoo.com (N. Ka

1 Present Address: Department of Chemical Scienc

0734-9750/$ – see front matter © 2013 Elsevier Inc. Allhttp://dx.doi.org/10.1016/j.biotechadv.2013.01.002

a b s t r a c t

a r t i c l e i n f o

Article history:Received 13 September 2012Received in revised form 28 December 2012Accepted 4 January 2013Available online 12 January 2013

Keywords:ElectrospinningCellulose acetateNanofiberTissue engineeringBiomolecule immobilizationBiosensingSelf-cleaning textileAntimicrobialBioseparationBioremediation

Cellulose acetate (CA) has been a material of choice for spectrum of utilities across different domains rangingfrom high absorbing diapers to membrane filters. Electrospinning has conferred a whole new perspective topolymeric materials including CA in the context of multifarious applications across myriad of niches. In thepresent review, we try to bring out the recent trend (focused over last five years' progress) of research onelectrospun CA fibers of nanoscale regime in the context of developmental strategies of their blends andnanocomposites for advanced applications. In the realm of biotechnology, electrospun CA fibers have foundapplications in biomolecule immobilization, tissue engineering, bio-sensing, nutraceutical delivery, bioseparation,crop protection, bioremediation and in the development of anti-counterfeiting and pH sensitivematerial, photocat-alytic self-cleaning textile, temperature-adaptable fabric, and antimicrobial mats, amongst others. The presentreview discusses these diverse applications of electrospun CA nanofibers.

© 2013 Elsevier Inc. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4222. Electrospinning-the basics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4223. Electrospinning cellulose acetate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423

3.1. Selection of solvent system and process optimization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4233.2. Electrospinning CA in presence of other polymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4243.3. Electrospinning CA with nanomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4253.4. Electrospinning CA for preparation of other nanomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425

4. Applications of electrospun cellulose acetate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4264.1. Immobilization of bioactive substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 426

4.1.1. Vitamin and enzyme immobilization platforms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4264.1.2. Drug loaded electrospun materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4274.1.3. Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428

4.2. Cell culture and tissue engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4294.3. Nutraceutical delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4314.4. Anti-counterfeiting and pH sensitive material . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4314.5. Optical device/biosensor application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4314.6. Photocatalytic self-cleaning textile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4314.7. Temperature-adaptable fabrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4324.8. Nanomaterials loaded antimicrobial mat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432

ax: +91 3712267006.rak).es, Tezpur University, Napaam, Sonitpur, Assam-784028, India.

rights reserved.

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4.9. Bioseparation and affinity purification membranes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4334.10. Bioremediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433

5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435

Fig. 1. Graph showing the number of documents on search query ‘electrospinning+cellulose acetate’ retrivable from SciFinder® on 10th September 2012.

1. Introduction

Polymeric nanocomposites and polymeric nanomaterials havecarved a unique niche in a plethora of domains including catalysis(Karak et al., 2010), surface coating (Konwar et al., 2010), antimicrobialagents (Konwarh et al., 2011a), enzyme immobilization (Konwarh etal., 2009; Konwarh et al. 2010a), drug delivery (Konwarh et al.,2010b), multifunctional biomaterial (Konwarh et al., 2012) and so on.It is pertinent to mention that an ever-increasing thrust on the globalscientific community is to opt for various bioresources that would confer‘green credentials’ (Das et al., 2012a) to the research output along withmeeting the demands for novel materials, which holds true for thebiotechnology sector (Das et al., 2012a,b; Kalita and Karak, 2012;Konwarh et al., 2011b) as well. In this context, the ubiquitous natureand abundance have endowed a special niche to cellulose (the greenestavailable polymeric material) and cellulose based materials (Misra etal., 2011) both in the industrial and biomedical realms. Amongst others,cellulose acetate (CA) (acetate ester of cellulose) has awide array of ap-plications ranging from cigarette filters to high absorbent diapers,semi-permeable membranes for separation processes and fibers andfilms for biomedical utiliites. CA fibers have remained focal point of re-search in multiple industries including the textile and more recently inthe biomedical domain.

According to a recent report by Global Industry Analysis, theworldwide market of cellulose acetate is projected to about 1.05 millionmetric tons by 2017 (http://www.strategyr.com/Cellulose_Acetate_Market_Report.asp) and themajor global players include Celanese Corpo-ration, Daicel Corporation, Primester, Eastman Chemical Company amongothers. Cellulose acetate exhibits a wide range of properties (Edgar 2004)attesting its importance in polysaccharide research. The most commonlevel of degree of substitution of ~2.45–2.5 confers good solubility (inwide varieties of solvent systems) and melt properties (Fischer et al.,2008). Puls et al. (2011) have pointed out the eco-compatibility of cellu-lose acetate based materials assessed in terms of their biodegradabilityas a function of the synergy between photodegradation, biodegradationand physical design of consumer products. Recently, Sousa et al. (2010)have presented a dynamical study (by dielectric relaxation spectroscopy,DRS), focused on the subglass mobility in cellulose acetate under twostructurally/morphologically different forms: the initial polymeric stateand structured membrane. CA fiber has comparatively high modulusand adequate flexural and tensile strength (Aoki et al., 2007). Graftingwith functional groups like \COOH, \SO3H and \NH2 endows anotherinteresting property to CA i.e., surface complexation with heavy metalions (Liu and Bai, 2006).

Exploring the multi-fold material properties of cellulose acetate inthe nanoscale regime is an interesting proposition. Amongst others,electrospinning has coferred awhole newperspective to the applicationof CA fibers. The simple and highly efficient technique of electro-spinning is apt for producing polymer nanofibrous membranes withhigh surface-to-volume ratio and high surface roughness (Pham et al.,2006). In 1934, Formhals (1934) attempted the electrospinning ofCAfibers using acetone as the solvent. The literature database, SciFinder®returned 176 references for the search query ‘electrospinning+celluloseacetate’ on 10th September, 2012. The year-wise categorization of thereferences over the last five years is shown in Fig. 1. Electrospun CA fibershave come a long way and recent literature suggests the applicationsacross a spectrum of domains.

In this review we try to bring out the recent trend in explorationand exploitation of electrospun CA fibers in the nanoscale for variousbiotechnological applications. Before we delve into the multifacetedapplications of electrospun CA fibers, it would be fruitful to illustratethe basics of electrospinning.

2. Electrospinning-the basics

Electrospinning has been associated with the epithet of ‘fascinatingfiber technology’ (Bhardwaj and Kundu, 2010). It has been used as asuccessful tool to spin a myriad of synthetic and natural polymers into30–2000 nmfibers extending uptomany kilometers in length. A typicalelectrospinning apparatus is schematically illustrated through thecentral image while the prospective applications of electrospun CAare shown in the peripheral images of Fig. 2. The basic apparatus consistsof a syringe pump, a high voltage supply and a collector. Application of anelectric field using high voltage source causes induction of chargeswithin a polymer solution (held at a needle tip at a certain distancefrom the collector by surface tension), resulting in charge repulsion.The latter overcomes the surface tension with eventual initiation of ajet. As pointed out by Renekar and Chun (1996), the jet comprises offour regions: the base, the jet, the splay and the collection. In the baseregion emerges the Taylor cone, the shape of which depends on thecomplex balance between the surface tension of the liquid and theforce of the electric field. Solutions with higher conductivity are moreconducive to jet formation. The polymer jet is accelerated and stretcheddue to the electric forces with eventual decrease in the diameter corre-sponding to increase in its length. During the flight of the jet, the solventevaporates and anappropriate collector can beused to capture the poly-mer fibers. It has also been hypothesized that radial charge repulsionslead to ‘splaying’ of the jet into a number of small fibers of nearlyequal diameter and charge per unit length (Renekar and Chun, 1996).The number of splays eventually dictates the final diameter of theelectrospun fibers. However, high speed photography has revealed

Fig. 2. Schematic representation of electrospinning cellulose acetate nanofibers (at the centre) and myriad of biotechnological applications (peripheral images) as discussed in the text.

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that the ‘splay’ is in fact a single, rapidly whipping jet (Shin et al., 2001a,b), the behavior of which depends upon three instabilities: the classicalRayleigh instability and two ‘conducting’ modes- dictated either bysurface tension or electric forces (Hohman et al., 2001a,b).Electrospinning process can be manipulated by three classes ofparameters:

a) Solution properties (conductivity/solution charge density, surfacetension, viscosity/concentration, polymermolecularweight, dielectricconstant and dipole moment).

b) Machine parameters (field strength/voltage, distance between tipand collector, flow rate, needle tip design and placement, collectorcomposition and geometry).

c) Ambient parameters (temperature, humidity and air velocity).

Kumar et al. (2012) and Pham et al. (2006) have reviewed theseparameters and their complex interplay in details with respect tomyriad of polymeric nanofibers and as such these do not form a subjectmatter of the present review. Nevertheless, it is pertinent to mentionoptimization of these parameters is a prerequisite to fine tune theshape-size accord of the electrospun fibers.

Electrospinning of cellulose and cellulose acetate has been exten-sively reviewed previously (Frey 2008). However, the last five years(2008–2012) have witnessed tremendous progress particularly inthe preparation of electrospun CA based composite materials, whichhold tremendous potential to wheel a number of industrial sectors.Literature databases like SciFinder®host a number of reports on variousnovel electrospinning protocols and development of electrospun CAbased advanced polymeric blends and nanocomposites for industrial

and biomedical domains. It is quite a mammoth task to focus on eachsynthesis approach of electrospinning CA as reported by variousworkers and as such this shall not be dealt with in details in the presentcompilation. Nevertheless, an effort has been made to highlight thewide spectrum of electrospun CA related research works of the recentyears. The subsequent section starts with citation of few reports onthe selection of appropriate solvent system for electrospinning CA andprocess optimization. This is followed byhighlights on the developmentof various polymer blends and nanocomposites of electrospun CA. Thearray of biotechnological applications has been dealt with separately.

3. Electrospinning cellulose acetate

A focal point of research over the years has been the selection ofsolvent system for electrospinning CA fibers.

3.1. Selection of solvent system and process optimization

The selection of appropriate solvents has been conventionallybased on trial and error, results from similar systems or solubilitymodels limited by physico-chemical database (Haas et al., 2010).Tungprapa et al. (2007b) have reported the effect of various singleand mixed solvent systems on the morphology and fiber diameter.The single solvent system comprised of acetone, chloroform, N,N-dimethylformamide (DMF), dichloromethane (DCM), formic acid,methanol (MeOH) and pyridine. Acetone–dimethylacetamide (DMAc),chloroform–MeOH, and DCM–MeOH were among the mixed solventsystems. The shear viscosity, surface tension, and conductivity of these

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solvent systems have been evaluated to be critical solution parametersin generating bead free or beaded fibers. Even ternary solvent system ofacetone/DMF/trifluro-ethanol has also been evaluated for electro-spinning cellulose acetate (Ma and Ramakrishna, 2008). More recently,compositional variation of a mixed solvent system of acetic acid/waterhas been found to dictate the size distribution of the electrospun CA(Han et al., 2008). Electrospinning of CA in presence of poly(ethyleneglycol) (PEG), poly(ethylene oxide) (PEO) and hydroxyapatite hasbeen assessed using DMAc/acetone, DMF, DMF/dioxane and aceticacid/acetone systems (Lee et al., 2009). A key observation wasforwarded by Haas et al. (2010) regarding the role of solvent volatilityin controlling the felt structure of electrospun CA. In this work, theapplication of Hansen's theory of solubility to select non-toxic binarysystems, optimized for manufacturing of electrospun CA fibre networkswith adjustable degree of fibre fusion merits special mention in thecontext of green nanotechnology. High packing density was obtainedwith binary low-volatile alcohols/methyl-ethyl ketone (MEK) solventmixtures, a decreased spinning distance and an increased feed rate. Ina recent work by Rodriguez et al. (2012), ribbon like morphology wasnoted for the CA fibers produced from acetone and mixture of ace-tone/isoporopanol (2:1) while electrospinning in acetone/DMAc (2:1)system resulted in the cylindrical shape. The group has reported an in-teresting power law relationship of 0.26 between the solution flow rateand the CA fiber size for 17% CA in acetone/DMAc (2:1).

There are not many reports available on the influence of ambientparameters and electrospinning parameters on the nature ofelectrospun CA fibers. The average diameter of electrospun CAnanofibers was found to increase with increase in humidity. On theother hand, temperature dictates the solvent evaporation rate and vis-cosity of the polymer solution. Both these parameters were found tohave profound influence on the fiber diameter of electrospun CA (DeVrieze et al., 2009). The effect of different parameters including fieldstrength, tip-to-collector distance, solution feed rate and compositionon the morphology of electrospun CA fibers was reported by Theopistiand Charalabos (2010). At this juncture the authors would like todraw the attention of the readers to the utility of statistical toolslike response surface methodology for optimizing electrospun fiberdiameters of titanium dioxide (Ray and Lalman, 2011) and silk(Amiraliyan et al., 2009) and so on. In this context, we have recentlyreported the use of Box-Behnken design technique to optimize few se-lected process parameters for minimizing the diameter of electrospunCA (Konwarh et al., 2013). Fiber morphology and size distributionwere found to be influenced by voltage, tip-to-collector distance andfeed rate of the polymeric solution prepared in acetic acid/water solventsystem.

A growing interest on the development of electrospun CA asblends and composites has been witnessed in the last few years(2008–2012). A myriad of natural and synthetic polymers andnanomaterials have been electrospun along with CA. This has beendescripted in the subsequent sub-sections. Furthermore, the writeup also highlights the fact that electrospinning of CA can be used effec-tively for the generation of other nanomaterials like activated carbonnanofibers.

3.2. Electrospinning CA in presence of other polymers

A plethora of synthetic and natural polymers have been electrospunwith CA. These are highlighted underneath.

Highly angulated ultrafine CA fibers with unique architecturalfeatures of nanometer-size shperulites and sub-micron size ridgesand grooves were prepared from mixtures of CA and poly(vinylpyrrolidone) or PVP (in DMF) and subsequent removal of the latter. Onthe other hand, nanoporous fibers were generated on electrospinningCA in presence of ß-cyclodextrin and its subsequent removal (Zhangand Hsieh, 2008). Preparation of electrospun CA, poly(vinyl pyrrolidone)PVP and their composite membranes with ribbon and cylindrical

morphology of CA and PVP fibers respectively has been reported. Prob-able diffusion of PVP in water in a washing step of CA/PVP/CA fibrousmembrane with water was exploited to generate micro-tubular struc-ture. Interestingly CA/PVP/CA fibrous composite membrane showed alower value of strain at break (%) and a higher value of tensile strength(MPa) compared to PVP/CA/PVP membrane (Castillo-Ortega et al.,2010). In a myriad of applications, CA nanofibers based biosensorcome into contact with various liquids and as such a high degree ofwicking rate is desired to transport liquid to its destination (Khatri etal., 2012). In this context, double nozzle system for independently jettingCA and PVA, was used for electrospinning of CA/PVA blended nanofibers.The wicking rate analysis of the regenerated cellulose post deacetylationof the blended fibers revealed the enhancement of the wicking rate as afunction of PVA solution concentration (Khatri et al., 2012).

Amongst others, cellulose acetate/polyurethane composite fiberswere reported to show a co-continuous nanofiber structure due tophase separation in the spinning solution of DMac/acetone and inthe course of electrospinning. PU contributed to the tensile strengthof the CA/PU mats while the dimensional stability and rigidity wasimproved by the semirigid component—CA (Tang et al., 2008). An im-portant illustration of the influence of surface chemistry and roughnessof electrospun CA fibers on epoxy matrix was put forth by Liao et al.(2011). Rough surface with multiple hydroxyl groups of CA fibers facil-itated strong adhesion in CA/epoxy and CA-polyurethane (PU)/epoxycomposites while severe interfacial debonding and fiber pullouts werenoted for PU/epoxy composites, attributed to the smooth PU surface.These differential interactions also dictated the visible light transmit-tance of the composite films- the best and the poorest optical propertywas observed for CA/epoxy and PU/epoxy films respectively.

In order to improve the mechanical properties of electrospun CAfibers, the action of poly(Bu acrylate) (PBA) was investigated. PBAacted as adhesive and resulted in generation of point-bonded structuresin the fibrous mats with significant increase in the tensile strength(Baek et al., 2011). Chen et al. (2009a) reported the variation in thediameter (1000 to 1750 nm) of smooth, cylindrical electrospuncomposite fibers based on CA and PEG with variation of molecularweight of the latter. The elongation and tensile strength ofelectrospun CA/PEO blend (20 wt.% PEO) was significantly improvedon incorporation of ZnO nanoparticles (Pittarate et al., 2011). Quanet al. (2009) reported the preparation of biodegradable electrospunpoly(butylene succinate)/CA blend while Du and Hsieh (2009)reported the preparation of dibutyryl chitin (DBC), CA and DBC/CAhybrid nanofibers, ranging from 30 to 350 nm in diameter using1:1 acetone: acetic acid solvent system. Hydrolysis with 5 N NaOHat 100 °C for 3 h regenerated cellulose/chitosan hybrid nanofibers.In yet another work, rejection of sodium chloride was found to increasesubstantially with increasing number of alternatively deposited elec-trostatic multilayers of chitosan/sodium alginate and chitosan/poly(styrene sulfonate) sodium salt on an electrospun CA fiber mat(Ritcharoen et al., 2008).

In order to circumvent the multi-step procedures to generatesurface functionality onto electrospun fibers, single-step fabrica-tion of hydroxyl functional groups onto electrospun poly(ethyleneterephthalate) (PET) with CA and cellulose has been reported. Liquidphase deposition and electrospraying techniques resulted in differentialdeposition pattern of metal oxide nanoparticles on the blends, sugges-tive of their hydroxyl functionality compared to pristine PET surface(Sundarrajan and Ramakrishan, 2010).

In a simple approach, mats of electrospun cellulose based fibers(cellulose acetate and hydroxypropyl cellulose) were deposited ontransparent conductive oxide covered glass plates. Liquid crystal devicesbased on thesepolymericmaterialswere obtainedby enclosing anematicliquid crystal E7 between two such plates (Rosu et al., 2011). The workdemonstrated the optical transmission dependence on the D.C. electricfield and temperature, simultaneously with the thermo-stimulatedcurrents.

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The use of a two-fluid coaxial electrospinning was reported byXiangyu et al. (2010) to obtain nonwoven core-shell structured technicallignin/CA nanofibers. They reported that concentration, viscosity, con-ductivity and flow rate ratio to bemajor players in dictating the fabrica-tion of the nanofibers. The core liquid in the internal concentric layerconsisted of technical lignin and polyacrylate dissolved in DMF whileacetic acid solution of CA was used as the shell solution. The researchgroup reported superior mechanical and thermal properties of thecoaxial fibers in comparison to the conventional lignin fibers.

Modulations in spinnability and morphology of silk fibroin (SF)/CAfiber felt were reported with respect to variation in CA content (Zhouet al., 2011b). Uniform, bead free fibers were generated with 10% CAcontent while discontinuous, sticky and beaded, dendritic morphologywas observed for CA content greater than 30%. A very important observa-tion that emanated out of this study was the induction of conformationtransition of SF molecules from random coil to ß-sheet by addition ofsmall quantity (not more than 10%) of CA.

3.3. Electrospinning CA with nanomaterials

In an endeavor to develop novel metal containing electrospun CAfibers, electrospinning was used to disperse quasi-spherical goldnanoparticles, prepared by trisodium citrate mediated reduction ofHAuCl4, into cellulose acetate ultra-fine fibers by electrospinning(Zhao et al., 2012a). In another report, CA/Fe2O3 composite nanofibrousmaterials for potential applications in separation processes wereprepared by electrospinning of 20% (w/v) CA solutionwith dispersedFe2O3 nanoparticles at concentrations varying between 1.4% and 4.5%(Tsioptsias et al., 2010). The addition of iron oxide did not have signifi-cant effect on the electrospun cellulose acetate fiber diameter due tocompetitive effects of viscosity and conductivity increments. Althoughincorporation of iron oxide nanoparticles was found to increase thethermal stability of cellulose acetate, the information onmagnetometricparameters of the composite material was not reported. Treatment ofdeacetylated electrospun cellulose acetate with sodium choloroacetateyielded anionic cellulose fibers and subsequent UV irradiation of thelatter, dipped in silver nitrate solution led to controlled surface-deposition of spherical silver nanoparticles (Birbach et al., 2008).Electrospinning has also been successfully used for the preparation offluorescent CA fibers (300–700 nm)withwell dispersed CdTe quantumdots (QDs) (Zhao et al., 2012b). As expected, X-ray diffraction studyattested the improved crystallinity of the fibers on incorporation ofthe QDs.

Cellulose nanocrystals (CNs) are known for their uniquemorphology,high surface area and favorable response to stress. In thismilieu, Cao andLucia (2010) reported the alkaline hydrolysis of electrospun CA/CNcomposite fibers to generate cellulose/CN composite nanofibers.

On the other hand, core-shell electrospinning has been used to pre-pare thermostable polyacrylonitrile (PAN) and CA based nanofibers(Fig. 3) with high loading of carbon nanotube (Lisunova et al., 2010).Multi-walled carbon nanotube (MWCNT) reinforced cellulose fiberswith high strength and Young's modulus were reported post de-acetylation of electrospun CA incorporated withMWCNT. Heat inducedannealing and cross linking between the surface carboxylic groups ofMWCNT and the cellulose hydroxyl groups enhanced the interfacialinteractions between the cellulosic matrix and the reinforcingnanomaterial (Lu and Hsieh, 2010a). In another of their recent works,the group reported well aligned MWCNTs along the fiber axis of theelectrospun CA. Even a very low loading of 0.55 wt.% MWCNTs was in-strumental in increasing the specific surface area (from 4.27 m2/g to7.69 m2/g), mechanical properties and water wettability of the fibers(228 nm in diameter) (Lu and Hsieh, 2010b).

Actuators are used to move or control a mechanism or system. Inthis context, well dispersed fullerene reinforced electrospun CAnanofiber based composite was assessed for its utility as dry-typeactuator. Substantial increment in tensile strength and three-fold

increase in tip-displacement even with 0.5 wt.% fullerene under bothA.C. and D.C. conditions raised the prospects of using the composite asefficient actuator (J. Li et al., 2011a).

At this juncture, a specialmentionmust bemade of POSS (polyhedraloligomeric silsesquioxane) technology—derived from a continuallyevolving class of compounds closely related to silicones. Improvementin the physical properties of polymers via impregnation of POSSsegments is attributed to the latter's ability to regulate the motionsof the chains without compromising with the processability andmechanical properties of the base polymer. Nanometric POSS distribu-tion into electrospun CA matrix compared to micrometer-sized POSScrystals in castfilms established the superiority of electrospinning to in-corporate POSS into polymer matrix (Cozza et al., 2010). The differencein affinity between the polymer matrix and the POSS in the twoapproaches was highlighted in terms of the solvent evaporationmechanism during electrospinning-leading to nanofiber productioncharacterized by a silsesquioxane dispersion similar to that present insolution.

3.4. Electrospinning CA for preparation of other nanomaterials

Electrospinning of CA has also been exploited for the preparation ofother nanostructuredmaterials for advanced applications. The followingcitations stand testimony to this.

Activated carbon nanofibers (ACNF) were prepared through theprocess of stabilization, short time carbonization and activationusing electrospun blended fibers of polyacrylonitrile (PAN) and CA.The capacitance of the rough surfaced CA-blended ACNF (CN15)was almost 73% higher than smoother CA free ACNF (CN). This wasattributed to the mesoporous high surface area resulting from blendingand electrospinning, and microporous structure of the former and thelatter respectively (Ju et al., 2008). Multichannel hollow carbon fibers(90–190 nm) were generated by utilizing the pyrolytic characteristicand phase separation behavior of CA with PAN. The strategy involvedthe electrospinning of binarymixture of PANandCA, removal of the latterand subsequent carbonization of the remaining PAN (Zhang and Hsieh,2009).

Electrospinning precursor solution of zinc acetate/cellulose acetatein mixed solvent system of DMF/acetone and subsequent calcinationof the precursor ZnAc/CA composite were used to fabricate ZnOnanofiber and nanoparticle. With a high contact area, the nanostruc-tured ZnO displayed strong photocatalytic activity, evaluated in termsof photodegradation of dye molecules such as Rhodamine B and Acidfuchsin (Liu et al., 2008). Cellulose acetate has also been used as fibertemplate for electrospinning photocatalytic TiO2/ZnO compositenanofibers for decomposition of Rhodamine B and phenol (R. Liu etal., 2010a).

With thermal emissivity above 90%, zirconium carbide (ZrC)nanofibers were electrospun for prospective use as thermal storagebarrier membrane by dissolving zirconium acetyl acetonate andcellulose acetate in glacial acetic acid and 2,4-pentadione as commonsolvents (Nam et al., 2009). Gallium Nitride (GaN) nanofibers wereelectrospun from a precursor solution composed of gallium nitrateand cellulose acetate. Thermal decomposition under nitrogen flow at400 °C and subsequent nitridization under ammonia at 900 °C of theelectrospun fibers generated gallium nitride fibers having crystallinewurtzite structure with diam. of 20 nm to few hundred nanometers.Conductance of single nanofibers increased with time of sinteringunder ammonia as revealed by I–V studies (Melendez et al., 2009).

The authors of the present compilation would like to draw the at-tention of the readers that the afore-cited works are not exhaustive.However, they would also like to point out the gradual increase in thenumber of patents (Table 1) on electrospinning of cellulose acetate. Inthe subsequent section, we have tried to highlight specifically themultifaceted applications of electrospun CA in the domain ofbiotechnology.

Fig. 3. TEM images of the PAN/CNTs (a and c) and CA/PAN–CNTs (b and d) nanofibres (Reproduced with permission from reference (Lisunova et al., 2010). Copyright 2010 Elsevier).

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4. Applications of electrospun cellulose acetate

4.1. Immobilization of bioactive substances

Yoo et al. (2009) have extensively reviewed the various physicaland chemical approaches for surface functionalization of electrospunnanofibers for drug delivery and tissue engineering. Amongst others,surface graft polymerization, plasma treatment, wet chemical method,and co-electrospinning of surface active agents and polymers representthe different surface functionalization strategies. Amyriad of biocatalysts,polysaccharides, cytokines and anti-cancer drugs have been surfaceimmobilized or entrapped within the interior of the fibers. It is alsopertinent to note that certain cell specific bioactive ligands immobilized

Table 1List of few recent patents associated with electrospun CA fibers.

Patent number Patent year Patent title

PT 104094 A 20091209 2009 Production of cellulosic nanofibers by electroCN 101538775 A 20090923 2009 Method for manufacture of modified electro

membrane with good mechanical strength.KR 2010090565 A 20100816 2010 Manufacturing method of biodegradable oxi

deacetylation, and oxidation of cellulose aceJP 2010121238 A 20100603 2010 Manufacturing apparatus of nanofibers by elCN 102166483 A 20110831 2011 Method for preparation of molecularly impriCN 102000363 A 20110406 2011 Method for preparing cellulose acetate/chito

biocompatibility.KR 2011032510 A 20110330 2011 Method for manufacturing nanofibers of cell

with good mechanical and structural properCN 102409484 A 20120411 2012 Method for preparation of modified polyviny

acetate nanofiber membrane

onto the surfaces of electrospun nanofibers enhance cell adhesion, pro-liferation, and differentiation.

In this context, electrospun CA nanofibers have instigated tre-mendous interest as immobilizationmatrix for a number of bioactivemoieties including biocatalysts and drugs on one hand while theprospects for tissue engineering are being realized gradually on theother. Few of the representative immobilized biomolecules areshown in Fig. 4.

4.1.1. Vitamin and enzyme immobilization platformsAmongst others, Vitamin A and vitamin E exhibit multifarious

biological action and protective roles. Taepaiboon et al.'s (2007)work merits a special mention, where in the research team has

Inventor/Reference

spinning of liquid crystal solutions. Godinho et al. (2009)spun nylon/cellulose acetate nanofiber Zhu et al. (2009)

dized-cellulose nonwoven fabric by electrospinning,tate.

Kim et al. (2010)

ectrospinning. Inai et al. (2010)nted nanofiber membrane for detection of rhodamine B. L. Li et al. (2011b)san/carbon nanotubes composite nanofiber with good Shen et al. (2011)

ulose acetate containing montmorillonite by electrospinningties.

Han et al. (2011)

l pyrrolidone/cellulose Li et al. (2012a)

Fig. 4. A few representative biomolecules that have been used to functionalize electrospun cellulose acetate fibers (for details, refer to the text).

427R. Konwarh et al. / Biotechnology Advances 31 (2013) 421–437

immobilized these two vitamins onto electrospun CA nanofibers(247–265 nm) with smooth and round cross-sectional morphology.The authors have highlighted on the gradual and monotonous increasein the cumulative release of the vitamins over the test period from theelectrospun fibers in sharp contrast to their burst release from the cor-responding as-cast films of cellulose acetate.

Immobilization of biocatalysts onto nanomaterials and polymericmaterials has its own diverse aspects. Enzyme immobilization in itselfis a multi-billion business. Electrospun CA nanofibers on hydrolysisand subsequent oxidation by NaIO4 (to generate surface aldehydegroups under statistically optimized parameters) acted as suitableimmobilization platform for Candida rugosa lipase (X J. Huang et al.,2011c). The authors have reported significant increment in thermosta-bility and durability post immobilization in comparison to the free coun-terpart. In yet another system, using glutaraldehyde as the couplingagent, C. rugosa lipase was covalently attached to cellulose membrane(containing pentaethylenehexamine (PEHA) as spacer) regeneratedfrom electrospun CA (Chen et al., 2011b). The authors have reported ahigh activity (9.83×104U/m2) of this biphasic enzyme-immobilizedmembrane bioreactor (EMBR) for the reaction model involving the hy-drolysis of olive oil.

Lu and Hsieh (2009) reported the preparation of a highly efficientand versatile porous support for enzyme immobilization using lipaseas model enzyme. Electrospun CA nanofibers (average diameter of200 nm) were subjected to alkaline hydrolysis. Nucleophilic reaction

of the resultant cellulose hydroxyl with triazinyl chloride of CibacronBlue F3GA (CB) affinity ligand facilitated the facile lipase loading ofabout 150 mg/g of the resultant membrane under optimized condi-tions. The adsorbed lipase had similar catalytic rate with retention of86.2% activity as in its free state. In this context, presence of magneticiron oxide nanoparticles in the cellulose acetate nanofibers (Tsioptsiaset al., 2010) would further ensure an additional industrial advantageof recyclability.

4.1.2. Drug loaded electrospun materialsElectrospinning has particularly carved a unique niche of its own

for drug delivery systems, after the first report in 2002 (Kenawy etal., 2002). Significant reduction in the systemic absorption of thedrugs and localized therapeutic effect at low drug concentration(Cui et al., 2010) for skin and wound healing applications are beingensured via appropriate electrospun fibers. It is pertinent to mentionthat although characterized by easy administration, the most commonform of drug delivery via the oral route suffers from a number of draw-backs—poor bioavailability due to hepatic metabolism, probability ofrapid high and low blood level spikes and the need for high and/or fre-quent dosing (Chien, 1992). In this context, a number of recent worksfocus on the use of electrospun CA mats for transdermal drug delivery(TDD). TDD refers to topically (using skin as the port of entry) adminis-teredmedicaments in the formof patches that deliver drugs for systemiceffects at a predetermined and precisely controlled rate, improves

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patient compliance and reduce inter and intra patients' variability(Kumar, 2011).

Naproxen (NAP), indomethacin (IND), ibuprofen (IBU), andsulindac (SUL) (Tungprapa et al., 2007a) have been loaded ontoelectrospun ultrafine fiber (263–297 nm) mats of CA. These smoothfibers swelled in acetate buffer system post incubation at 37 °C for24 h. The release profile of the drugs, as tested by total immersionmethod followed the trend: NAP>IBU>IND>SUL. A myriad of factorsdictate the drug-release profile from a polymer matrix including thesolubility of the drug in the polymer matrix, the solubility of the drugin the testing medium, the swelling behavior and the solubility of thepolymer matrix in the testing medium, the diffusion of the drug fromthe polymer matrix, etc. Generally, the smaller the difference in thesolubility parameter (δ), which bears correspondence to the cohesiveenergy density of a compound, between the two components is, thegreater theirmiscibilitywill be (Tungprapa et al., 2007a,b). In yet anotherstudy, a stable 6 days in vitro release of ester prodrugs of naproxen,including ester, ethyl ester and isopropyl ester loaded onto electrospunCA nanofibers (100–500 nm) has been recently reported (Wu et al.,2010).

Coaxially electrospun CA and poly(vinyl pyrrolidone) membraneshave been assessed for the controlled release application of amoxicillinin gastrointestinal administration and for transdermal patches(Castillo-Ortega et al., 2011). Recently, the research team reported theoptimized conditions for preparation of the composite. The tensilestrength of the fibers was not affected by the presence of amoxicillinalthough the rigidity decreased considerably. pH dependent studyrevealed an increase from 61% to 79% in the release profile (obeyinga diffusion mechanism) of amoxicillin with increase in the pH from3.0 to 7.2 respectively (Castillo-Ortega et al., 2012).

Suwantong's group (Suwantong et al., 2007) has reportedcurcumin loaded smooth electrospun CA nanofibers (within a sizespectrum of 314–340 nm), compatible with normal human dermalfibroblasts, vouching for use as topical or transdermal patch. The integ-rity as assessed by 1H nuclear magnetic resonance spectrophotometryand bioactivity in the context of free radical scavenging potency ofcurcumin was retained even after subjecting to a high electrospinningpotential for loading onto the mat. They have found that the releaseprofile of the drug varies in total immersionmethod and transdermaldiffusion through pig skin, with low drug release in the latterprocess.

An important study in this domain is the loading of wound-healingmediators, asiaticoside (in the form of crude extract or pure substance)and curcumin onto electrospun CA fiber mats (Suwantong et al., 2010).An interesting observation was the differential attachment, proliferationand morphology of fibroblast cells cultured onto these drug-loadednanofibers that were stable upto 4 months on storage. Cells culturedon asiaticoside loaded fibers appeared spindle-shaped while they wereround on curcumin loaded mat. This vouches for the regulatory effectof differentially functionalized electrospun cellulose acetate mat onphenotypic attributes in cell-culture. The proliferation of the cells wasattested by high amounts of collagen synthesized by them.

In an effort to overcome the poor water solubility (11.5 mg/mL) ofgallic acid (3,4,5-trihydroxybenzoic acid) (endowed with multiplebio-protective action) and promote its release into the skin, the suit-ability of electrospun CA fibers was assessed. The documented drug-loading-dependent toxicity of the material towards human fibroblastcells calls for low loading of drug in topical products. Scanning electronmicroscopic imaging attested the low-biodegradability of the fibersalthough their degradation by bacterial-lipase like enzymes hasbeen claimed (Phaechamud and Phiriyawirut, 2011). There existsscant and conflicting evidence on the efficacy of Silymarin, an extractof milk thistle, commonly used to treat chronic liver disease (Tzenget al., 2012). Nevertheless, diffusion mediated monotonous releaseof silymarin has been observed from silymarin-loaded electrospunCA fibers (550–900 nm) (Phiriyawirut and Phaechamud, 2012).

Ketoprofen [2-(3-benzoylphenyl) propionic acid] is a benzophenone-derived non-steroidal anti-inflammatory drug. A zero-order release pro-file of ketoprofen from drug-loaded electrospun CA fibers produced byusing a modified coaxial electrospinning process (comprising of theuse of a sheath solvent) has been recently reported (Yu et al., 2012).

Alkannin, shikonin (A/S) and their derivatives are naturally occurringhydroxynaphthoquinones. They have a well-established spectrum ofwound healing (Papageorgiou et al., 2008), antimicrobial, anti-inflammatory, antioxidant and antitumor activity. In this context, thesedrugs (A/S) were loaded onto electrospun cellulose acetate nanofiberswithout considerably affecting the morphology and the mean diametersize (Kontogiannopoulos et al., 2011). The authors have reported ahigh drug entrapment and appropriate release profiles, rendering themapt for topical/transdermal wound healing dressings. The plausiblefuture scope could be the exploitation of the bioactivity of the constitu-ents for tissue engineering scaffolds for repairing and regeneration. Onthe other hand, a long-term antimicrobial effect for wound healingapplication was noted (Liu et al., 2012) for nanofibrous membranesprepared from CA and polyester urethane (PEU) impregnated withpolyhexamethylene biguanide (PHMB), a polymer used as a disinfec-tant and antiseptic.

Chlorhexidine, a bactericidal agent was immobilized onto submicronelectrospun cellulose acetate through the approach of curing by organictitanate, Tyzor TE (TTE) (coupling agent) in presence of water vapor(Chen et al., 2008). PEO was incorporated to facilitate electrospinning ofthe N, N-dimethylformamide solutions. The contact bactericidal activity(in terms of zone of inhibition) against E. coli and S. epidermis washighlighted in the context of a simple diffusion model. In a yet anotherreport, electrospun CA nanofiber fabrics containing anN-halamine anti-microbial agent of bis(N-choloro-2,2,6,6-tetramethyl-4-piperidinyl)sebacate (CI-BTMP) showed better antimicrobial efficacy than solutioncast films containing identical amounts of CA and CI-BTMP. Further-more, the composite fiber fabrics also displayed excellent mammalcell viability (Sun et al., 2010).

At this juncture, it is pertinent to mention about the due consider-ation received by a close relative of cellulose acetate i.e., cellulose ace-tate phthalate (CAP), a pharmaceutical excipient used as an entericcoating agent for tablets and capsules for pH dependent release ofdrugs to develop anti-HIV-1 strategies (Das et al., 2010). It forms gp41six-helix bundles resulting in a terminal, functionally inactive viral com-ponent (Neurath et al., 2002). Recently, electrospun CAP fibers loadedwith anti-HIV drugs (TMC 125 and Viread) exhibited a much strongerinhibition of HIV-1 infection than the pristine fibers (Huang et al.,2011a). The drugs could be easily released by human semen. These re-sults forward the use of the electrospun CAP fibers (non-toxic to vaginalepithelian cells and vaginal Lactobacilli) in preventing HIV-1 spreadduring sexual intercourse.

4.1.3. MiscellaneousThe following examples highlight the use of bioconjugated

electrospun CA fibers for crop protection and insect control.2,6-dicholoro-4-nitroaniline (DCNA) is widely used to countercheck

Rhizopus rot on sweet potato roots, fruits of cherries, peaches andfoliage diseases of vegetable crops caused by Botrytis spp. and Sclerotinaspp. In this context, smooth DCNA loaded electrospun CA nanofibershave been fabricated successfully (Thitiwongsawet et al., 2010). The re-tention of the integrity of the as-loaded DCNA in the carrier CA matswas confirmed by 1H-nuclear magnetic resonance spectroscopicstudy. It was interesting to note a greater amount of water retention,weight loss, and DCNA release from the electrospun carrier mats thanthe DCNA-loaded as cast-films.

With the objective of harnessing the various functional properties(including antibacterial, antifungal and mosquito-repellence) ofCitronella (Cymbopogon nardus) essential oil, Silveira et al. (2012))have reported its successful loading onto electrospun CA fibers. Thedefect-free morphology, as revealed by scanning electron microscopic

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imaging, was facilitated by modulations in viscosity and evaporationrate of precursor solutions formulated with the oil. Thermogravimetricanalysis had shown the thermal properties were not influenced signifi-cantly post oil loading.

The ecological hazards associated with applications of insecticidesfor crop protection needs no further elaboration. As an answer to thisissue, applications of pheromones—the chemical substances for mes-sage relay among insects, is considered to be a novel approach to con-trol insect infestation. The strategy is to disorient male insects fromthe females to suppress reproduction via the dispensing of selectedpheromone (mostly sex pheromones) across a field using sprays (forfunctionalized fluid containing the pheromone) or pheromone loadedsolid particles or dispensers at specific location for evaporation of thechemical messenger. However, such techniques suffer from a numberof disadvantages (Hellmann et al., 2011). In this context, the applicationof beaded electrospun CA fiber mats loaded with as high as 33 weightpercentage of pheromones in the cropfields has been proposed recent-ly (Hellmann et al., 2011). A linear release profile of the pheromoneswas noted over a period of time spanning couple of weeks. The re-search group had estimated the requirement of about 1 g ofnanofibers per hectare and growing season post assumption of 33%pheromone loading on the biodegradable fibers. They have proposedthat a tractor-bound multijet electrospinning set-up may be used forthe distribution of the nanofibers in about 20 min per hectare.Hellmann et al. (2011) are hopeful about the on-going field investiga-tion on vineyards for obtaining realistic data, both on pheromone releaseprofile as well as potential risks originating from degradation processes.

4.2. Cell culture and tissue engineering

One of the important directions of tissue engineering is the designof polymeric scaffolds with specific chemo-mechanical properties toprovide a spatially and temporally regulated dynamic influence onthe phenotype and other cellular behavior by providing indirect anddirect informational signalling cues. Cui et al. (2010) have recentlyreviewed the prospects of electrospun nanofibers for tissue engineering.The existence in 3D niche and interaction with extracellular matrix(ECM) components at nano length scale in vivo may be underpinningthe differential response of cells subjected to be grown on 3D electro-spun nanofibrous environments and 2D smooth surfaces. Modulationof factors such as interfiber distance or alignment that affect thecell migration pattern, surface functionalization that affects regionsof contact guidance, gradient organization and rate of biodegradability(that should preferentially coincide or at least amenable to mimic therate of neo-tissue formation) are to be duly considered to improvebiomechanical properties of electrospun nanofibers for tissue engineeringapplications. Well-established biocompatibility with documented im-provement via cationic functionalization (Hofmann et al., 2006;Miyamoto et al., 1989), mechanical properties and stability in physiolog-ical environment post gamma sterilization and agingmarshals in supportof the suitability of cellulose based materials as tissue engineering matrix(Bartouilh de Taillac et al., 2004; Pajulo et al., 1996). However,most of thebiomedical utilities are reported for bacterial produced cellulose,regenerated cellulose sponges and solution spun cellulose fiber (lyocell)which offer poor amenability to tune the size in the nano or micro scalerange. In this context, electrospinning may be envisaged as an effectivemode to generate cellulose based filamentswith control in shape-size ac-cord for tissue engineering applications. However, it is pertinent to men-tion that although there is a plethora of reports on the apt choice ofcellulose as membranes for hemodialysis, carriers for pharmaceuticalsand drug-releasing scaffolds with registered use in both hard and softtissue engineering and myriad other biomedical applications (Czaja etal., 2007), the application of electrospun CA nanofibers for tissue en-gineering is not quite well elaborated in literature databases as ofnow. Nevertheless, the following references stand in support of the

growing endeavor to bring electrospun CA in the domain of cell cultureand tissue engineering.

Recently, saponification of electrospun CA mat (with diameters inthe range of 200 nm to 1.5 μm) has been successfully executed for thegeneration of novel scaffolds to nucleate bioactive calcium phosphate(Ca\P) crystals as a function of surface chemistry for future bonehealing applications (Rodríguez et al., 2011). Remarkably, the crystalstructure of the nucleated calcium phosphate exhibited a diffractionpattern resembling that of hydroxyapatite, the mineralized componentof bone. Increasing the negative charge (COO\) via carboxymethylcellulose (CMC) treatment or aqueous heating treatment in the presenceof calcium ions augmented the biomimetic coating of Ca\P crystals onthe electrospun fibers (Fig. 5). Mineralization within simulated bodyfluid indicated that cellulose scaffolds could be made into a bioactivesubstrate, amenable for bone tissue engineering applications. The foun-dation for effective implantation in orthopaedic application of such ma-terials shall lie in the close juxtaposition between bone and theimplanted surface i.e., osteointegration. Liu et al. (2011) have presentedan interesting report on the mineralization behavior of CaCO3 crystalson electrospun CA fibers. The shape-size accord of the nanoscalebuilding blocks of CaCO3 was dictated by the concentration ofpoly(acrylic acid) (PAA)—a crystal growth modifier (Fig. 6). Onthe other hand, the removal of the CA fibers led to the formationof CaCO3 microtubes.

A very important inference was put forth (Rubenstein et al. 2010)regarding the direct dependence of human umbilical vein endotheli-al cells (HUVECs) growth within and adhesion to and migrationthroughout sheath (S)-core(C) electrospun CA/chitosan (CA-S/CA-C, Chito-S/Chito-C, CA-S/Chito-C) based scaffolds on themechan-ical stiffness of the latter. Chitosan was added to increase the me-chanical stiffness of the scaffolds while fibronectin was added asan additional specific ligand for endothelial cells. The authors havereported the bulk mechanical properties of dual-polymer scaffolds (rib-bon-like morphology of the fibers) to have better fit with that of the na-tive extracellular matrix. The work highlighted the advantage ofdual-polymer scaffolds over traditional single-polymer scaffolds interms of greater tunability of mechanical properties of the bulk scaffoldwithout affecting the biocompatibility. Pre-seeding the scaffoldswith en-dothelial cells prior to implantation, with subsequent in vivo interactionof platelets and endothelial cells, new vascular network could beassisted.

Deacetylation, oxidation and reductive amination of electrospunCA generated chondroitin sulphate-mimicking polyelectrolyte fibermeshes that supported the proliferation and chondrogenic differentia-tion of primary human marrow stromal cells (hMSC) in vitro as ana-lyzed by the expression level of mRNA transcripts of chondrogenicmarker genes—type II collagen, Sox-9 and aggrecan using real timeRT-PCR (Dragulescu-Andrasi et al., 2008).

Hydroxyapatite added electrospun CA membranes were preparedin an endeavor to develop biocompatible and biodegradable scaffoldsfor microvascular cell growth. The interesting aspect of the work wasthe use of eggshells—low cost natural calcium source for the prepara-tion of hydroxyapatite—the natural ceramic of the human skeletalsystem (Balazsi et al., 2009). On the other hand, Gouma et al. reportedthe enhanced human osteoblast attachment, spreading and prolifera-tion on hybrid membrane of electrospun CA with nanoaggregates ofhydroxyapatite (Gouma et al., 2010).

Eichhorn et al. (2010) reported the alignment of fibroblast cells onaligned electospun CAnanofibers. Furthermore, the extracellularmatrixwas found to be deposited in the alignment direction. Report on thegrowth of Schwann cells assisted by parallel line surface topographiccues of cellulose acetate butyrate (CAB) fibers, electrospun using ace-tone and N,N′-dimethylacetamide (Huang et al., 2011b) has openedup new route to culture nerve cells for neural engineering and repairs.The authors have proposed that the surface voids can be attributedto the fast evaporation of acetone, a highly volatile solvent. On the

Fig. 5. SEM of mineralized scaffolds without CMC pretreatment a) 45 min regeneration time, b) 24 h regeneration time, c) 45 min regeneration time combined with treatment at80 °C, pH 8 for 2 h, and d) same as c but with 24 h regeneration time. (Reproduced with permission from reference (Rodríguez et al., 2011). Copyright 2011 American ChemicalSociety.)

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other hand, the high viscosity of the residual solution after acetoneevaporation ensures the surface lines to be maintained. The authorshave tried to focus on the differential growth of the cells as a functionof alignment of the fibers. Furthermore, the early adherence andelongation of the Schwann cells on the parallel lined scaffolds merita special mention in comparison to the requirement of longer time forattachment and growth on smooth surface.

In yet another report, adhesion and growth of ECV304 and 3 T3cells on in situ (using UV curing technology) photo cross-linked fibersof methylacrylated cellulose acetate butyrate (CABIEM) was reportedto increase with the increase in the collagen percentage (Cakmakci etal., 2011).

Fig. 6. SEM images of the electrospun CA fibers after CaCO3 mineralization for 10 days (Cross-sectional view of a single CaCO3-coated CA fiber (top right) and a photograph of the CApanel c shows the electrospun CA fiber. (d) High-magnification image of the surface of a singreference (Liu et al., 2011). Copyright 2011 American Chemical Society.)

As a highly versatile technique to prepare functional nanomaterialswith tunable properties, layer by layer (LbL) approach (DeRocher etal., 2010) can be used to modulate the thickness, morphology andcomposition of the targeted materials via alterations in the numberof the polymer deposition cycles and changing the composition ofthe layer component. LbL techniquehas been instrumental in assemblinga host of materials like polymers and biomolecules onto a myriad ofsubstrates. A hybrid technique comprising of electrospinning andelectrospraying has been recently used for the LbL assembly of nega-tively charged CA and positively charged chitosan (Li et al., 2012b).The mats exhibited commendable cell compatibility and no cytotoxicityfor the mouse lung fibroblasts cells. Interestingly, the number of

a, b) without and (c, d) with the PAA present in CaCl2 solutions. Insets in panel c:fiber scaffold with uniform CaCO3 coatings (bottom left). The white arrow in the inset ofle fiber in panel c. [CaCl2]=20 mM, [PAA]=1 g L−1. (Reproduced with permission from

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deposition layers and composition of outermost layer influenced theadhesion and spreading of the cells.

4.3. Nutraceutical delivery

Certain food ingredients (e.g., vitamins, probiotics, functionallipids and amino acids) also have physiological roles. These bioactivecomponents (Wildman, 2001) make up ‘functional foods’ which havea role beyond normal nutrition. The indispensability is the protectionduring storage of the bioactive components, processing and storage ofthe functional foods and eventually during gastrointestinal transitprior to their entry in the target site post ingestion (Faulks andSouthon, 2008). Micro and nanoencapsulation technology (Augustinand Hemar, 2009) ensures the protection of these ingredients againstheat, moisture and pH until their site-specific and time targeted release.In this context, electrospun nanofibres can be instrumental in foodsector as vectors for nutrients, protective entities for encapsulatedactive compounds during food processing and bio-separation mate-rials to enhance food safety. Recently electrospun edible nanofibrousmats (Wongsasulak et al., 2010) have been prepared from blend so-lutions of CA in acetic acid and egg albumin in formic acid, via thefine tuning of electrical conductivity and surface tension by additionof Tween40® (surfactant). It is pertinent to mention that use of eggalbumin, an excellent source of proteins, to develop fibrous nutra-ceutical carriers facilitate to withstand stomach's severe acidic con-ditions and release the bioactive material at the alkaline pH of theintestine.

In another report (Sakuldao et al., 2011), release mechanism ofgelatin (a common gelling agent in food, pharmaceuticals and cosmeticmanufacturing) from coaxially electrospun core-shell CA fibers wasfound to be anomalous diffusion and exhibited a near zero order releasepattern with release half-life of ~7.4 days. Interestingly, the fibrousfilms immersed in PBS for 20 days were found to be intact (withoutbursting). The membranes have been envisaged as suitable matrix forsustained release of proteinaceous pharmaceutical/food compounds inthe gastro-intestinal tract.

4.4. Anti-counterfeiting and pH sensitive material

Stimuli-sensitive materials show enormous potential across multipledomains. Developing unique nanomaterial-based protocol for taggingand identifying legitimate items is viewed as an answer to the issue ofcounterfeiting in the global market. In this pursuit, Hendrick et al.(2010) have successfully loaded florescent silica nanoparticles, Cornelldots (C dots) with tetramethylrhodamine (TRITC) core into electrospunCA nanofibers. The use of dual-emission core-shell nanoparticle sensornanoparticle has apparent advantages of high surface area, high porosity,biocompatibility and ease of functionalizationwith stability of the loadedflorescent dye. The researchers have proposed the prospective use ofsimilar system with TRITC core and FITC (fluorescein isothiocyanate)surrounding the silica shell in the C dots for monitoring sweat pH instudying hydration levels—a critical aspect in physiology research anddomains like performance of sportspersons. C dot loading did not affectthe mechanical attributes of the electrospun fibers. These pH-sensingnanoparticles could be used as ratiometric device within the electrospunfibers as evidenced from confocal microscopic studies. However, the C

Fig. 7. Fluorescence micrographs of CA–NO2SP nanofibers: (a) without UV irradiation, (b) i(Reproduced with permission from reference (S. Liu et al., 2010b). Copyright 2010 Elsevier

dots are dispersible in myriad of solvents; their dispersibility in strongacids and bases is limited due to dissolution of the silica shell.

4.5. Optical device/biosensor application

Photochromic nanofibers (with excellent photosensitivity) areperceived as excellent material for applications in optical devices(Yao et al., 1992) and/or biosensors. Irradiationwith light of appropriateenergy causes changes in molecular structure or conformation ofphotochromic materials eventually altering the UV–visible (UV–Vis)absorption spectra (Tork et al., 2001). Preparation and delving of thephotoregulation (under irradiationwith UV light) of photofunctional cel-lulose derivatives containing photochromicmoieties such as azobenzene,cinnamate and spiropyran have been reported (Arai et al., 1996; S. Liu etal., 2010b). Furthermore, bacterial cellulose nanofibrous membranes,surface modified with spiropyran photochromes have been preparedfor prospective applications in sensitive displays and optical devices(Hu et al., 2011).

In this context, the establishment of photochromic property ofelectrospun complex of cellulose acetate (CA)-1′,3′,3′-trimethyl-6-nitrospiro (2H-1-benzopyran-2,2′-indoline) (NO2SP) in acetone (Fig. 7)has ushered in a newchannel of application for the electrospunmaterials(Liu et al., 2010a,b). Although infrared (IR) spectral analysis was sugges-tive of significant hydrogen bonding between CA and NO2SP, the latter'sincorporation did not influence the fiber morphology. The switchingfrom a ring-closed, colorless spirogyran form to a ring-opened, stronglycolored merocyanine form (with greater hydrophilicity than spiroform) due to the photocleavage of the spiro C\O bond endowed thenanofiberswith the reversible photochromic property. A specialmentionmust be made of the reversibility of the photochromic effect asevidenced from the observation of color recovery and water contactangle.

As a matter of fact, the sensitivity of quenching-based fluorescentoptical sensors is largely dictated by the accessibility of the sensingelements to the quencher or the analyte. Electrospun fibers withhigh surface-area-to-volume ratiomay serve not only as good platformsfor localizing and immobilizing sensing elements but also ensureoptimal exposure to the quenchers. Polymer thin film optical sensorfor extremely low concentrations (ppb) of methyl viologen and cyto-chrome c in aqueous solutions was developed using electrostaticlayer-by-layer adsorption of fluorescent probe, hydrolyzed poly[2-(3-thienyl) ethanol butoxy carbonyl-methyl urethane] (H-PURET)onto the surface of electrospun cellulose acetate (CA) nanofibrousmembranes (Wang et al., 2004).

4.6. Photocatalytic self-cleaning textile

The concept of self-cleaning textiles can be traced to the Lotus effect(Bhushan, 2012). The microscale bumps and nanoscale hair-like projec-tions complemented by the leaf's waxy chemical composition assist thelotus plant to self-clean by repelling water and dirt andward off bacteriaand other contaminations. In thismilieu, nanotechnology has gone a stepahead to mimic such self-cleaning attribute via surface modifications ofdifferent polymeric materials. The use of photocatalyst is envisaged asan advantageous tool to impart self-cleaning property to textiles, therebycircumventing additional laundering action. Titania treatment has been

rradiated for 20 s, (c) irradiated for 40 s (d) irradiated for 60 s, (e) irradiated for 80 s..)

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conventionally employed to test the self-cleaning property (Uddin et al.,2008) of natural cotton, chemically modified cotton and wool-like fibersat radiation mimicking the sun's spectrum at relatively high intensities.Creation of excited electrons in the conduction band and holes inthe valence band post absorption of photons initiates photocatalysis,with subsequent generation of reactive radical species. The efficacyof the titania photocatalyst is handicapped in conventional treatmentof textiles by the obvious low surface to volume ratio. In order tocircumnavigate this snag, CA (core phase) with nanocrystallineTiO2 dispersion has been coaxially electrospun into sheath phase byBedford and Steckl (2010). Even after deacetylation, no apparent effecton photocatalysis of the titania was observed. It is an interesting obser-vation that self-cleaning is seldom tested in light of longer wavelengthsand lower intensities, somewhat similar to indoor working ambience.While, designing the experimental protocol, the research group hastaken advantage of titania's superior properties in charge-pair recombi-nation lifetime, interfacial charge transfer rate, and near band gap lightabsorption (Hoffmann et al., 1995). In this context, they have reportedthe degradation of a blue dye solution under halogen lamp irradiation,somewhat due to better resemblance to the indoor light conditions(Fig. 8). With prospective application for toxic chemical decomposition(Štengl et al., 2005), this coaxially electrospun, self-cleaning textile(that exhibited complete dye-degradation in 7–8 h, out-performingthose made by conventional loading procedures that registered only20% dye degradation) is bound to fetch further delving in health, envi-ronmental and military applications.

4.7. Temperature-adaptable fabrics

Investigation of thermo-regulating capacity of electrospun PEG/CAcomposites demonstrated a reproducible and balanced thermal storageand release properties. Here in, PEG was used as a model phase changematerial (PCM) and CA as the supporting material. Phase change fibers

Fig. 8. Photographs showing the discoloration of Keyacid Blue (0.1 wt.%) stain in coaxialelectrospun non-woven mats of CA (core) \TiO2 (sheath) fibers exposed to halogenlight (~13 mW/cm2) over a period of 24 h. (Reproduced with permission from reference(Bedford and Steckl, 2010). Copyright 2010 American Chemical Society).

impart desirable thermal storage and release properties to fabrics (Huet al., 2006). Although techniques like microencapsulation has been in-troduced in order to improve the reliability and thermal behaviors onrepeated thermal cycles, the result was the subsequent stiffening ofthe surface coated fabrics and decrease in tactile comfort (determinedby the total value) perceived by humans. As an answer to these techni-cal challenges, research is directed to the suitability of electrospinning(Wang et al., 2010). In this context, Chen et al. have recently reportedthe preparation of electrospun ultrafine PEG/CA fibers as phase changecomposite for application in thermal energy storage (Chen et al.,2011a). The authors have reported the changes in morphology andthermal attributes as a function ofmodulated PEG content. Most impor-tantly, test of repetitive heating-cooling thermal cycles to stimulate dra-matic temperature change condition demonstrated commendablecapacity of the electrospun fibers to regulate their interior temperaturewith the altered ambient temperature. The research team (Chen et al.,2009b) has reported the improvement in water-resistant ability andthermal stability of shape-stabilized PEG/CA composite fiberscrosslinked by the use of toluene-2,4-diisocyanate, TDI. In this context,it would be interesting to evaluate the effect of PEGylation at lowerdoses on the thermo-mechanical attributes of CA fibers.

4.8. Nanomaterials loaded antimicrobial mat

The association of myriad of infections and diseases (Ales et al.,2009) with various microbes does not need further elaboration. Anumber of sectors including food, textile, packaging and health careproducts are confronted by microbial contamination (Li et al.,2008). This has accelerated research on antimicrobial surface coatingamong other things. It is pertinent to mention that electrospun com-posite nanofiber fabrics containing uniformly dispersed antimicrobialagents having large surface to mass ratios are instigating interest asantimicrobial polymeric materials with durable, non-leachable andbiocompatible attributes. More importantly, the ability to withstandadverse processing conditions in comparison to the organic counterpartshas attested special attention to inorganic antimicrobial agents (Yuvarajet al., 2010). Although the mode of anti-microbial action of silvernanoparticles is a highly debated area, a number of plausiblemechanismshave been proposed (Lara et al., 2011). Both silver nanoparticles (Chunget al., 2008) and silver ions (Liau et al., 1997) are capable of modulatingthe three dimensional structure of proteins by interacting with S\Sbonds, consequently obstructing microbial cellular operations includingcell wall synthesis, protein synthesis and nucleic acid synthesis. Further-more, probing of proteomic data (Lok et al., 2006)was suggestive of accu-mulation of envelope protein precursor and dissipation of proton motiveforce, complemented by depletion of intracellular ATP (Dibrov et al.,2002).

Biocidal nanobiocomposites of CA with antimicrobial agents likesilver and zinc nanoparticles have been reported recently. In thiscontext, Son et al. (2006) have reported the preparation ofelectrospun cellulose acetate nanofibers (average diameter of 610 nm)with surface-decorated silver nanoparticles. The fibers with Ag nano-particles (average size of 21 nm) exhibited excellent antibacterial actionagainst Gram-positive S. aureus and Gram-negative E. coli, K. pneumoniaeand P. aeruginosa assessed by the nonwoven fabric attachment method.Though theworkers have not highlighted the difference in the antimicro-bial efficacy against the two classes of bacteria, they have reported a re-duction of the Gram negative bacteria (responsible for almost 80% ofthe various infections) by almost 99.9% post 18 h. The formation of thenanoparticles has been discussed under the sequential steps of diffusionof the Ag+ ions and Ag clusters generated on the surface, followed byaggregation to form Ag nanoparticles post photoreduction by UV irradi-ation. Apart from photocatalysis, exploration of other green routes likephytoextract (Barua et al., 2013; Konwarh et al., 2011a) mediated insitu reduction of metal salts for preparation of nanoparticle decoratedCA fibers seems to be interesting proposition.

Fig. 9. TEM image of the composite fiber and SAED patterns (inset in the left top of thefigure). The ZnO nanoparticles are clearly seen in surface of the fibers. (Reproducedwith permission from reference (Anitha et al., 2012). Copyright 2012 Elsevier).

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In yet another recent work, electrospun multifunctional anti-bacterial ZnO nanoparticles embedded CA membranes (Fig. 9) havebeen prepared (Anitha et al., 2012). The bactericidal effect of ZnOagainst Gram positive and Gram negative bacteria (Tam et al., 2008) iswell established. Although ineffective against K. pneumoniae, thecomposite membrane exhibited 27 mm, 22 mm and 14 mm zoneof inhibition against methicillin resistant S. aureus (MRSA), E.coliand Citrobacter freudii respectively (Fig. 10). The differential actionof both silver nanoparticles and zinc oxide nanoparticles againstthe two bacterial groups is often ascribed to the basic architecturaldifferences between their cell walls (Konwarh et al., 2010a). Neverthe-less, electrospun fibers with high surface area for contact (determiningthe antibacterial activity of the biocidal agent), and dispersion stabilityof the homogeneous and monodispersed ZnO nanoparticles in theCA fibers were envisaged for the high antimicrobial efficacy of thereported nanocomposite. Another attractive feature of the preparedcomposite was the inherent superhydrophobic (without any additionalsurface treatment) surface, vouching for its application as self-cleaningtextile. Furthermore, being a direct wide band gap semiconductor(Eg=3.4 eV), ZnO (with a high exciton binding energy of about60 meV) is a likely candidate for stable room temperature luminescentand lasing devices. The PL spectra did not reveal significant alterationsin the optical properties in pristine and ZnO embedded CA matsZnO exhibits two prominent peaks: UV near-band-edge (NBE) withpeak emission at around 380 nm and a deep-level (DL) emission inthe visible region. However, the authors have reported an interesting

Fig. 10. Images of bactericidal effect of (a) pure fibrous CA membrane and (b) ZnO embedaureus (MRSA) and Gram-negative E. coli, Citrobacter freundii, Klebsiella pneumonia. (Reprod

observation of quenching of the visible emission in the PL spectrawhich was suggestive of the surface passivation of ZnO with CA(Jan-Peter et al., 2008).

4.9. Bioseparation and affinity purification membranes

Zhang et al. (2008) have evaluated the prospects of electrospun CAnanofiber (tens of nanometers to microns in diameter) felts (withpore size ranging from sub-microns to microns) as an ion exchangemedium for protein separations. Surface functionalization of regeneratedcellulose nanofibers, obtained post hydrolysis/deacetylation of CA fibers,with diethylaminoethyl (DEAE) anion exchange ligand conferred thehighest static binding capacity of 40 mg/g of bovine serum albumin(BSA) in comparison to 33.5 mg/g, 14.5 mg/g, and 15.5 mg/g for func-tionalized commercial membrane, cellulose microfiber medium andbleached absorbent cotton balls, respectively. Limitation of detrimentalsystem dispersion (as detected by calculation of the Peclet number)could be achieved via increasing the number of felt layers used forthe adsorption bed, without compromising pressure limitations. Akeypoint to note was the higher (26.9 mg/g) dynamic adsorption ofBSA, at 10% breakthrough, compared to the DEAE commercialmembrane(20.9 mg/g).

4.10. Bioremediation

Waste water treatment is a global concern. Heavy-metal inducedtoxicity at different levels of the food-chain and the issue of waterpollution has remained a focal point of research over a couple ofyears (Sud et al., 2008). Tian et al. (2011) have justified the use ofelectrospun CA membranes for heavy metal (Cu2+, Hg2+ and Cd2+)ion adsorption in water treatment in the context of its low cost/benefitratio. They have reported the availability of adsorptive \COOH groupson electrospun CA membranes by grafting poly(methacrylic acid)(PMMA) using Ce4+ initiated polymerization. Experiments on adsorp-tion were suggestive of higher adsorption at higher initial pH valueand high selectivity of the prepared membrane for Hg2+. The recycla-bility of the membranes has been ensured by using saturatedethylenedinitrilo tetraacetic acid solution facilitating the desorption ofthe adsorbed metal ions (Fig. 11). In another report, post ethanol treat-ment to increase the anti-felting properties, silk fibroin/CA electrospunblend nanofibrous membranes with randomly oriented fibers of100–600 nm diameter, showed exceptional performance (22.8 mgCu2+per g) for heavy metal adsorption (Zhou et al., 2011a).

Furthermore, polyelectrolyte multilayers assembled using polyelec-trolytes bearing carboxylic acid or amine groups can act as nanoreactors

ded CA fibrous membrane against Gram-positive methicillin-resistant Staphylococcusuced with permission from reference (Anitha et al., 2012). Copyright 2012 Elsevier).

Fig. 11. The photographs of CA-g-PMAA adsorbents (a) before adsorption of Cu2+, (b) after adsorption of Cu2+ and (c) after desorption of Cu2+ using EDTA saturated solution. And thephotograph of (d) non-modified electrospun CAmembrane after adsorption of Cu2+ is for comparison (Reproduced with permission from reference (Tian et al., 2011). Copyright 2011.

434 R. Konwarh et al. / Biotechnology Advances 31 (2013) 421–437

for complexation of metal ions and subsequent generation of inorganicnanoparticles within the multilayers. In this context, zero-valent ironnanoparticles (ZVI NPs) were immobilized onto electropsun cellulose ac-etate nanofibers assembled with multilayers of polyelectrolyte (PE) viz.,poly(diallyldimethylammonium chloride) (PDADMAC) and polyacrylicacid (PAA) through electrostatic layer-by-layer (LbL) assembly (Fig. 12)(Xiao et al., 2009). ZVI NPs are considered as a cost-effective and ecolog-ically benign agent for environmental remediation. The environmentalapplication of the mat was assessed by its potential to decolorize acidfuschin, an organic dye in dyeingwastewater. This approach for prepara-tion of the hybrid nanofibrous mats merits special mention in terms ofthe reusability and easy recyclability of the latter with no leaching ofthe ZVI NPs during remediation and storage. Generation of no secondarycontaminant on exposure of the reported filtration material to water is apractical advantage compared to colloidal ZVI NPs, prepared via conven-tional routes (Wang and Zhang, 1997).

5. Conclusion

Electrospinning has opened up new avenues for exploring theunique material properties of cellulose acetate. As noted in the re-spective sections, the prime focus over the recent years has been onthe development of novel preparative protocols, including advancedelectrospinning approaches and solvent systems, and electrospunCA based nanocomposites and blends. Approaches like ‘click chemistry’maybe employed for themodulation of the surface functionality. Devel-opment of semiconductor and magnetic composites of electrospun CA

Fig. 12. Schematic illustration of immobilizing ZVI NPs onto PE multilayer-assembled CA nanAmerican Chemical Society).

for various prospective applications could be interesting proposition.The ever-increasing number of reports attests the various avant-gardeapplications of the electrospunCAfibers acrossmultiple biotechnologicalniches from biomolecule immobilization to bioremediation. Futureinvestigations may be directed in comprehending the molecularlevel interaction of the various immobilized biomolecules and theCA fibers using various analytical and computational tools. Assessingthe degradability of electrospun CA is prerequisite particularly intissue-engineering applications. In this context, life cycle assessmentwould complement the real prospects of the commercial applica-tions of the various blends and composites of elctrospun CA fibers.

Acknowledgment

The authors are thankful to the Natural Sciences and EngineeringResearch Council (NSERC) Canada, Discovery Grant and the OntarioMinistry of Agriculture, Food and Rural Affairs (OMAFRA)/Universityof Guelph Bio-economy Industrial Uses Research Program for the fi-nancial support. Rocktotpal Konwarh acknowledges the receipt of Ca-nadian Commonwealth Scholarship from Canadian Bureau forInternational Education, Foreign Affairs and International Trade,Canada, DFAIT. He also expresses his gratitude to the Department ofBiotechnology, Government of India for his Senior Research Fellowship.The authors are also greatly indebted to Prof. A.K.Mohanty, Departmentof Plant Agriculture, University of Guelph, Canada for his encourage-ment, critical advice and support to complete this review.

ofibers (Reproduced with permission from reference (Xiao et al., 2009). Copyright 2009

435R. Konwarh et al. / Biotechnology Advances 31 (2013) 421–437

References

Ales PC, Milan K, Renata V, Robert P, Jana S, Vladimır K, Petr H, Radek Z, Libor K.Antifungal activity of silver nanoparticles against Candida spp. Biomaterials2009;30:6333–40.

Amiraliyan N, Nouri M, Kish MH. Electrospinning of silk nanofibers.I. an investigation ofnanofiber morphology and process optimization using response surface methodology.Fiber Polym 2009;10:167–76.

Anitha S, Brabu B, Thiruvadigal DJ, Gopalakrishnan C, Natarajan TS. Optical, bactericidal andwater repellent properties of electrospun nano-composite membranes of celluloseacetate and ZnO. Carbohydr Polym 2012;87:1065–72.

Aoki D, Teramoto Y, Nishio Y. SH-containing cellulose acetate derivatives: preparationand characterization as a shape memory-recovery material. Biomacromolecules2007;8(12):3749–57.

Arai K, Shitara Y, Ohyama T. Preparation of photochromic spiropyrans linked to methylcellulose and photoregulation of their properties. J Mater Chem 1996;6:11–4.

Augustin MA, Hemar Y. Nano- and micro-structured assemblies for encapsulation offood ingredients. Chem Soc Rev 2009;38:902–12.

BaekWI, Pant HR, Nam K-T, Nirmala R, Oh H-J, Kim I, Kim H-Y. Effect of adhesive on themorphology and mechanical properties of electrospun fibrous mat of cellulose acetate.Carbohydr Res 2011;346(13):1956–61.

Balazsi C, Bishop A, Yang JHC, Balazsi K, Weber F, Gouma P-I. Biopolymer-hydroxyapatitescaffolds for advanced prosthetics. Compos Interface 2009;16(2–3):191–200.

Bartouilh de Taillac L, Porte-Durrieu MC, Labrugere C, Bareille R, Amedee J, Baquey C.Grafting of RGD peptides to cellulose to enhance human osteoprogenitor cells adhesionand proliferation. Compos Sci Technol 2004;64:827–37.

Barua S, Konwarh R, Mandal M, Gopalakrishnan R, Kumar D, Karak N. Biomimeticallyprepared antibacterial, free radical scavenging poly(ethylene glycol) supported sil-ver nanoparticles as Aedes albopictus larvicidal agent. Adv Sci Eng Med 2013;5(4):201–8.

Bedford NM, Steckl AJ. Photocatalytic self cleaning textile fibers by coaxialelectrospinning. ACS Appl Mater Interfaces 2010;2(8):2448–55.

Bhardwaj N, Kundu SC. Electrospinning: a fascinating fiber fabrication technique.Biotechnol Adv 2010;28(3):325–47.

Bhushan B. Bioinspired Structured Surfaces. Langmuir 2012;28(3):1698–714.Birbach NL, Dong H, Hinestroza JP. Controlled deposition of silver nanoparticles on cel-

lulosic nanofibers. Abstracts of Papers, 235th ACS National Meeting. LA, UnitedStates: New Orleans; 2008. [Apri l6–10].

Cakmakci E, Gungor A, Kayaman-Apohan N, Kuruca SE, Cetin MB, Dar KA. Cell growth on insitu photo-cross-linked electrospun acrylated cellulose acetate butyrate. J Biomater SciPolym Ed 2011;23(7):887–99.

Cao X, Lucia LA. Fabrication and properties of cellulose/cellulose nanocrystal compositenanofibers. Abstracts of Papers, 239th ACS National Meeting. CELLCA, UnitedStates: San Francisco; 2010. [March 21–25].

Castillo-Ortega MM, Romero-Garcia J, Rodriguez F, Najera-Luna A, Herrera-Franco PJ. Fi-brousmembranes of cellulose acetate and poly(vinyl pyrrolidone) by electrospinningmethod: preparation and characterization. J Appl Polym Sci 2010;116(4):1873–8.

Castillo-Ortega MM, Nájera-Luna A, Rodríguez-Félix DE, Encinas JC, Rodríguez-Félix F,Romero J, Herrera-Franco PJ. Preparation, characterization and release of amoxicillinfrom cellulose acetate and poly(vinyl pyrrolidone) coaxial electrospun fibrous mem-branes. Mat Sci Eng C Mater 2011;31:1772–8.

Castillo-Ortega MM, Montano-Figueroa AG, Rodriguez-Felix DE, Munive GT,Herrera-Franco PJ. Amoxicillin embedded in cellulose acetate-poly (vinyl pyrrolidone)fibers prepared by coaxial electrospinning: preparation and characterization. MaterLett 2012;76:250–4.

Chen L, Bromberg L, Hatton TA, Rutledge GC. Electrospun cellulose acetate fiberscontaining chlorhexidine as a bactericide. Polymer 2008;49(5):1266–75.

ChenC,Wang L, HuangY. Role ofMn of PEG in themorphology andproperties of electrospunPEG/CA composite fibers for thermal energy storage. AIChE J 2009a;55(3):820–7.

Chen C, Wang L, Huang Y. Crosslinking of the electrospun polyethylene glycol/celluloseacetate composite fibers as shape-stabilized phase change materials. Mater Lett2009b;63(5):569–71.

Chen C, Wang L, Huang Y. Electrospun phase change fibers based on polyethyleneglycol/cellulose acetate blends. Appl Energy 2011a;88:3133–9.

Chen P-C, Huang X-J, Huang F, Ou Y, Chen M-R, Xu Z-K. Immobilization of lipase ontocellulose ultrafine fiber membrane for oil hydrolysis in high performance bioreactor.Cellulose 2011b;18:1563–71.

Chien YW. Novel drug delivery systems, Vol. 50. NY: Marcel Dekker, New York; 1992.Chung YC, Chen IH, Chen CJ. The surface modification of silver nanoparticles by phosphoryl

disulfides for improved biocompatibility and intracellular uptake. Biomaterials2008;29:1807–16.

Cozza ES, Monticelli O, Marsano E. Electrospinning: a novel method to incorporatePOSS into a polymer matrix. Macromol Mater Eng 2010;295(9):791–5.

Cui W, Zhou Y, Chang J. Electrospun nanofibrous materials for tissue engineering anddrug delivery. Sci Technol Adv Mater 2010;11(014108). [11pp.].

Czaja WK, Young DJ, Kawecki M, Brown Jr RM. The future prospects of microbial cellulosein biomedical applications. Biomacromolecules 2007;8(1):1-12.

Das NJ, Amiji MM, BahiaMF, Sarmento B. Nanotechnology-based systems for the treatmentand prevention of HIV/AIDS. Adv Drug Deliv Rev 2010;62:458–77.

Das G, Bordoloi NK, Rai SK, Mukherjee AK, Karak N. Biodegradable and biocompatibleepoxidized vegetable oil modified thermostable poly(vinyl chloride): thermaland performance characteristics post biodegradation with Pseudomonas aeruginosaand Achromobacter sp. J Hazard Mater 2012a;209–210:435–42.

Das G, Roy JK, Mukherjee AK, Karak N. Mesua ferrea L.seed oil modified sulfone epoxyresin and multi-walled carbon nanotube nanocomposites and their biomedicaland mechanical properties. Adv Sci Lett 2012b;4:1–9.

De Vrieze S, Van Camp T, Nelvig A, Hagstrom B, Westbroek P, De Clerck K. The effectof temperature and humidity on electrospinning. J Mater Sci 2009;44(5):1357–62.

DeRocher JP, Mao P, Han J, Rubner MF, Cohen RE. Layer-by-layer assembly of polyelec-trolytes in nanofluidic devices. Macromolecules 2010;43:2430–7.

Dibrov P, Dzioba J, Gosink KK, Hase CC. Chemiosmotic mechanism of antimicrobial ac-tivity of Ag(+) in Vibrio cholerae. Antimicrob Agents Chemother 2002;46:2668–70.

Dragulescu-Andrasi A, Ma Z, Ayers DC, Wixted JJ, Song J. Electrospun polysaccharidefiber meshes supporting the chondrogenic differentiation of human bone marrowstromal cells. Abstracts of Papers, 236th ACS National Meeting; 2008. p. CARB-048.[Philadelphia, PA, United States, August 17–21].

Du J, Hsieh Y-L. Cellulose/chitosan hybrid nanofibers from electrospinning of theirester derivatives. Cellulose 2009;16(2):247–60.

Edgar K. Organic cellulose esters. In: Mark HF, editor. Encyclopedia of polymer scienceand technology. 3rd edn. New York: Wiley; 2004. p. 129–58.

Eichhorn SJ, Gough JE, Dugan J. Aligned cellulose nanostructures for controlled tissuegrowth. Abstracts of Papers, 239th ACS National Meeting. CELLUnited States: SanFrancisco, CA; 2010. March 21–25].

Faulks RM, Southon S. Assessing the bioavailability of nutraceuticals. In: Garti N, editor.Delivery and controlled release of bioactives in foods and nutraceuticals. NewYork: CRC Press; 2008. p. 3-25.

Fischer S, Thummler K, Volkert B, Hettrich K, Schmidt I, Fischer K. Properties and appli-cations of cellulose acetate. Macromol Symp 2008;262:89–96.

Formhals A. Process and apparatus for preparing artificial threads; 1934 [US Pat.1975504].

Frey MW. Electrospinning cellulose and cellulose derivatives. Polym Rev 2008;48(2):378–91.

Godinho MHF, Canejo JPHG, Borges JPMR, Kundu S, Almeida PLMM, Pinto LFVV. Produc-tion of cellulosic nanofibers by electrospinning of liquid crystal solutions. Port PatAppl 2009;104094:20091209.

Gouma PI, Ramachandran K, Firat M, Connolly M, Zuckermann R, Balaszi C, Perrotta PL,Xue R. Novel bioceramics for bone implants. Cer Eng Sci Proc 2010;30(6):35–44.

Haas D, Heinrich S, Greil P. Solvent control of cellulose acetate nanofibre felt structureproduced by electrospinning. J Mater Sci 2010;45:1299–306.

Han SO, Youk JH, Min KD, Kang YO, Park WH. Electrospinning of cellulose acetatenanofibers using a mixed solvent of acetic acid/water: Effects of solvent compositionon the fiber diameter. Mater Lett 2008;62:759–62.

Han SO, Yoo YJ, Jung NJ, Kim HY, Kim SU. Method for manufacturing nanofibers of celluloseacetate containing montmorillonite by electrospinning with good mechanical andstructural properties. Repub Korean Kongkae Taeho Kongbo 2011;2011032510:20110330.

Hellmann C, Greiner A, Wendorff JH. Design of pheromone releasing nanofibers forplant protection. Polym Adv Technol 2011;22(4):407–13.

Hendrick E, Frey M, Herz E, Wiesner U. Cellulose acetate fibers with fluorescingnanoparticles for anti-counterfeiting and pH-sensing applications. J Eng FiberFabr 2010;5(1):21–30.

Hoffmann MR, Martin ST, Choi W, Behnemann DW. Environmental applications ofsemiconductor photocatalysis. Chem Rev 1995;95:69–96.

Hofmann I, Muller L, Greil P, Muller F. Calcium phosphate nucleation on cellulose fabrics.Surf CoatTechnol 2006;201:2392–8.

Hohman MM, Shin M, Rutledge G, Brenner MP. Electrospinning and electrically forcedjets I. Stability theory. Phys Fluids 2001a;13:2201.

Hohman MM, Shin M, Rutledge G, Brenner MP. Electrospinning and electrically forcedjets II. Stability theory. Phys Fluids 2001b;13:2221.

http://www.strategyr.com/Cellulose_Acetate_Market_Report.asp dated April 2012,accessed on May 2012.

Hu J, Yu H, Chen YM, Zhu MF. Study on phase-change characteristics of PET–PEGcopolymers. J Macromol Sci B 2006;45:615–21.

Hu W, Liu S, Chen S, Wang H. Preparation and properties of photochromic bacterialcellulose nanofibrous membranes. Cellulose 2011;18(3):655–61.

Huang C, Soenen SJ, van Gulck E, Vanham G, Rejman J, Van Calenbergh S, Vervaet C,Coenye T, Verstraelen H, Temmerman M, Demeester J, De Smedt SC. Electrospuncellulose acetate phthalate fibers for semen induced anti-HIV vaginal drug delivery.Biomaterials 2011a;33(3):962–9.

Huang C, Tang Y, Liu X, Sutti A, Ke Q, Mo X, Wang X, Morsic Y, Lin T. Electrospinning ofnanofibres with parallel line surface texture for improvement of nerve cell growth.Soft Matter 2011b;7:10812–7.

Huang XJ, Chen P-C, Huang F, Ou Y, Chen M-R, Xu Z-K. Immobilization of Candidarugosa lipase on electrospun cellulose nanofiber membrane. J Mol Catal B: Enzym2011c;3–4:95-100.

Inai R, Shinohara K, Aoki T. Manufacturing apparatus of nanofibers by electrospinning.Jpn Kokai Tokkyo Koho 2010;2010121238:20100603.

Jan-Peter R, Tobias V, Lars W, Ilja R, Jurgen G. Influence of polymer coating on thelow-temperature photoluminescence properties of ZnO nanowires. Appl PhysLett 2008;92:011103.

Ju Y-W, Na M-Y, Jung H-R, Lee W-J. Electrochemical performance of electrospun ACNFelectrodes using polymer blend. ECS Trans 2008;13(19):75–86.

Kalita H, Karak N. Bio-based elastomeric hyperbranched polyurethanes for shapememory application. Iran Polym J 2012;21:263–71.

Karak N, Konwarh R, Voit B. Catalytically active vegetable-oil based thermoplastichyperbranched polyurethane/silver nanocomposite. Macromol Mater Eng2010;295(2):159–69.

Kenawy ER, Bowlin GL, Mansfield K, Layman J, Simpson DG, Sanders EH, Wnek GE.Release of tetracycline hydrochloride from electrospun poly(ethylene vinylacetate), poly(lactic acid), and a blend. J Control Release 2002;81(1–2):57–64.

436 R. Konwarh et al. / Biotechnology Advances 31 (2013) 421–437

Khatri Z, Wei K, Kim B-S, Kim I-S. Effect of deacetylation on wicking behavior ofco-electrospun cellulose acetate/polyvinyl alcohol nanofibers blend. CarbohydrPolym 2012;87(3):2183–8.

Kim YS, Choi OG, Kang YS, Kim CH, Park JH. Manufacturing method of biodegradableoxidized-cellulose nonwoven fabric by electrospinning, deacetylation, and oxidationof cellulose acetate. Repub Korean Kongkae Taeho Kongbo 2010;2010090565:20100816.

Kontogiannopoulos KN, Assimopoulou AN, Tsivintzelis I, Panayiotou C, Papageorgiou VP.Electrospun fibermats containing shikonin and derivativeswith potential biomedicalapplications. Int J Pharm 2011;409(1–2):216–28.

Konwar U, Karak N, Mandal M. Vegetable oil based highly branched polyester/clay silvernanocomposites as antimicrobial surface coating materials. Prog Org Coat2010;68(4):265–73.

Konwarh R, Karak N, Rai SK, Mukherjee AK. Polymer-assisted iron oxide magneticnanoparticle immobilized keratinase. Nanotechnol 2009;20:225107.

Konwarh R, Kalita D, Mahanta CL, Mandal M, Karak N. Magnetically recyclable, antimicro-bial, and catalytically enhanced polymer-assisted “green” nanosystem-immobilizedAspergillus niger amyloglucosidase. Appl Microbiol Biot 2010a;87(6):1983–92.

Konwarh R, Saikia JP, Karak N, Konwar BK. ‘Poly(ethylene glycol)-magneticnanoparticles-curcumin’ trio: directed morphogenesis and synergistic free radicalscavenging. Colloid Surf B 2010b;81(2):578–86.

Konwarh R, Gogoi B, Philip R, Laskar MA, Karak N. Biomimetic preparation of polymer-supported free radical scavenging, cytocompatible and antimicrobial “green” silvernanoparticles using aqueous extract of Citrus sinensis peel. Colloid Surf B 2011a;84:338–45.

Konwarh R, Karak N, Sawian CE, Baruah S, Mandal M. Effect of sonication and aging onthe templating attribute of starch for “green” silver nanoparticles and their interac-tions at bio-interface. Carbohyd Polym 2011b;83(3):1245–52.

Konwarh R, Pramanik S, Devi KSP, Saikia N, Boruah R, Maiti TK, Deka RC, Karak N.Lycopene coupled ‘trifoliate’ polyaniline nanofibers as multi-functional biomaterial.J Mater Chem 2012;22:15062–70.

Konwarh R, Misra M, Mohanty AK, Karak N. Diameter-tuning of electrospun cellulose ace-tate fibers: a Box–Behnkendesign (BBD) study. Carbohydr Polym 2013;92(2):1100–6.

Kumar CG. A review of transdermal therapeutics system. IJPT 2011;3:1367–81.Kumar PR, Khan N, Vivekanandhan S, Satyanarayana N, Mohanty AK, Misra M.

Nanofibers: effective generation by electrospinning and their applications. J NanosciNanotechnol 2012;12(1):1-25.

Lara HH, Garza-Treviño EN, Ixtepan-Turrent L, Singh DK. Silver nanoparticles arebroad-spectrum bactericidal and virucidal compounds. J Nanobiotechnol 2011;9:30.

Lee KY, Jeong L, Kang YO, Lee SJ, Park WO. Electrospinning of polysaccharides for re-generative medicine. Adv Drug Delivery Rev 2009;61:1020–32.

Li Q, Mahendra S, Lyon DY, Brunet L, Liga MV, Li D, Alvarez PJ. Antimicrobialnanomaterials for water disinfection and microbial control: potential applicationsand implications. Water Res 2008;42(18):4591–602.

Li J, Kee C-D, Vadahanambi S, Oh I-K. A novel biocompatible actuator based onelectrospun cellulose acetate. Adv Mat Res 2011a;214:359–63.

Li L, Yuan Y, Zhang Z. Method for preparation of molecularly imprinted nanofibermembrane for detection of rhodamine B. Faming Zhuanli Shenqing2011b;102166483:20110831.

Li L, Xiang T, Zhang Z.Method for preparation ofmodified polyvinyl pyrrolidone/celluloseacetate nanofiber membrane. Faming Zhuanli Shenqing 2012a;102409484:20120411.

Li W, Xueyong L, Wei L, Ting W, Xiaoxia L, Siyi P, Hongbing D. Nanofibrous matslayer-by-layer assembled via electrospun cellulose acetate and electrosprayed chitosanfor cell culture. Eur Polym J 2012b. http://dx.doi.org/10.1016/j.eurpolymj.2012.08.001.

Liao H, Wu Y, WuM, Liu H. Effects of fiber surface chemistry and roughness on interfacialstructures of electrospun fiber reinforced epoxy composite films. Polym Composite2011;32(5):837–45.

Liau SY, Read DC, Pugh WJ, Furr JR, Russell AD. Interaction of silver nitrate with readilyidentifiable groups: relationship to the antibacterial action of silver ions. Lett ApplMicrobiol 1997;25:279–83.

Lisunova M, Hildmann A, Hatting B, Datsyuk V, Reich S. Nanofibres of CA/PAN with highamount of carbon nanotubes by core-shell electrospinning. Compos Sci Technol2010;70(11):1584–8.

Liu CX, Bai RB. Adsorptive removal of copper ions with highly porous chitosan/celluloseacetate blend hollow fiber membranes. J Membr Sci 2006;284(1–2):313–22.

Liu H, Yang J, Liang J, Huang Y, Tang C. ZnO nanofiber and nanoparticle synthesizedthrough electrospinning and their photocatalytic activity under visible light. J AmCeram Soc 2008;91(4):1287–91.

Liu R, Ye H, Xiong X, Liu H. Fabrication of TiO2/ZnO composite nanofibers byelectrospinning and their photocatalytic property. Mater Chem Phys 2010a;121(3):432–9.

Liu S, Tan L, HuW, Li X, Chen Y. Cellulose acetate nanofibers with photochromic property:fabrication and characterization. Mater Lett 2010b;64:2427–30.

Liu L, He D, Wang G-S, Yu S-H. Bioinspired crystallization of CaCO3 coatings onelectrospun cellulose acetate fiber scaffolds and corresponding CaCO3 microtubenetworks. Langmuir 2011;27:7199–206.

Liu X, Lin T, Gao Y, Xu Z, Huang C, Yao G, Jiang L, Tang Y, Wang X. Antimicrobialelectrospun nanofibers of cellulose acetate and polyester urethane composite forwound dressing. J Biomed Mater Res B Appl Biomater 2012;100(6):1556–65.

Lok CN, Ho CM, Chen R, He QY, YuWY, Sun H, Tam PK, Chiu JF, Che CM. Proteomic analysisof the mode of antibacterial action of silver nanoparticles. J Proteome Res 2006;5:916–24.

Lu P, Hsieh Y-L. Lipase bound cellulose nanofibrous membrane via Cibacron Blue F3GAaffinity ligand. J Membr Sci 2009;330(1+2):288–96.

Lu P, Hsieh Y-L. Multi-walled carbon nanotube (MWCNT) reinforced cellulose fibers byelectrospinning. Abstracts of Papers, 239th ACS National Meeting, 170. UnitedStates: San Francisco, CA; 2010a. [March 21–25].

Lu P, Hsieh Y-L. Multiwalled carbon nanotube (MWCNT) reinforced cellulose fibers byelectrospinning. ACS Appl Mater Interfaces 2010b;2(8):2413–20.

Ma Z, Ramakrishna S. Electrospun regenerated cellulose nanofiber affinity membranefunctionalized with protein A/G for IgG purification. J Membr Sci 2008;319:23–8.

Melendez A, Morales K, Ramos I, Santigo-Aviles JJ, Campo E. Preparation and propertiesof electrospun gallium nitride nanofibers. IEEE Conference on Nanotechnology,9th, Genoa, Italy; 2009. p. 269–72. [July 26–30].

MisraM, Seydibeyoğlu O, Ray D, Das K,Mohanty AK. Biodegradable nanocomposites fromcellulosic plastics and cellulosic fiber. In: Mittal Vikas, editor. Nanocomposites withbiodegradable polymers: synthesis, properties, and future perspectives. New York:Oxford University Press Inc.; 2011. [Chapter 6].

Miyamoto T, Takahashi S, Ito H, Inagaki H, Noishiki Y. Tissue biocompatibility of celluloseand its derivatives. J Biomed Mater Res 1989;23:125–33.

Nam YS, Cui XM, Jeong L, Lee JY, Park WH. Fabrication and characterization of zirconiumcarbide (ZrC) nanofibers with thermal storage property. Thin Solid Films2009;517(24):6531–8.

Neurath AR, Strick N, Jiang SB, Li YY, Debnath AK. Anti-HIV-1 activity of cellulose acetatephthalate: synergy with soluble CD4 and induction of “dead-end” gp41 six-helixbundles. BMC Infect Dis 2002;2:6.

Pajulo O, Viljanto J, Hurme T, Saukko P, Lonnberg B, Lonnqvist K. Viscose cellulosesponge as an implantable matrix: changes in the structure increase the productionof granulation tissue. J Biomed Mater Res 1996;32:439–46.

Papageorgiou VP, Assimopoulou AN, Ballis AC. Alkannins and shikonins: a new class ofwound healing agents. Curr Med Chem 2008;15(30):3248–67.

Phaechamud T, Phiriyawirut M. In vitro cytotoxicity and degradability tests of gallicacid-loaded cellulose acetate electrospun fiber. Res J Pharm Biol Chem Sci2011;2(3):85–98.

Pham QP, Sharma U, Mikos AG. Electrospinning of polymeric nanofibers for tissueengineering applications: a review. Tissue Eng 2006;12(5):1197–211.

Phiriyawirut M, Phaechamud T. Cellulose acetate electrospun fiber mats for controlledrelease of silymarin. J Nanosci Nanotechnol 2012;12(1):793–9.

Pittarate C, Yoovidhya T, Srichumpuang W, Intasanta N, Wongsasulak S. Effects ofpoly(ethylene oxide) and ZnO nanoparticles on the morphology, tensile and thermalproperties of cellulose acetate nanocomposite fibrous film. Polym J 2011;43(12):978–86.

Puls J, Wilson SA, Puls DH. Degradation of cellulose acetate-based materials: a review.J Polym Environ 2011;19:152–65.

Quan S-L, Kang S-G, Chin I-J. Electrospinning of poly(butylene succinate)/celluloseacetate blends. PMSE Preprints 2009;100:277–8.

Ray S, Lalman JA. Using the Box–Benhen design (BBD) to minimize the diameter ofelectrospun titanium dioxide nanofibers. Chem Eng Commun 2011;169:116–25.

Renekar DH, Chun I. Nanometre diameter fibres of polymer, produced by electrospinning.Nanotechnology 1996;7:216.

RitcharoenW, Supaphol P, Pavasant P. Development of polyelectrolyte multilayer-coatedelectrospun cellulose acetate fiber mat as composite membranes. Eur Polym J2008;44(12):3963–8.

Rodríguez K, Renneckar S, Gatenholm P. Biomimetic calcium phosphate crystal mineraliza-tion on electrospun cellulose-based scaffolds. ACS Appl Mater Interfaces 2011;3:681–9.

Rodriguez K, Gatenholm P, Renneckar S. Electrospinning cellulosic nanofibers forbiomedical applications: structure and in vitro biocompatibility. Cellulose2012;19(5):1583–98.

Rosu C, Manaila MD, Kundu S, Almeida PL, Danila O. Perspectives on the electrically in-duced properties of electrospun cellulose/liquid crystal devices. J Electrostat2011;69(6):623–30.

Rubenstein DA, Venkitachalam SM, FangWang DZ, Lu H, Frame MD, Yin W. In vitro bio-compatibility of sheath–core cellulose-acetate-based electrospun scaffolds towardsendothelial cells and platelets. J Biomater Sci Polym Ed 2010;21(13):1713–36.

Sakuldao S, Yoovidhya T, Wongsasulak S. Coaxial electrospinning and sustained releaseproperties of gelatin-cellulose acetate core-shell ultrafine fibres. ScienceAsia2011;37(4):335–43.

Shen M, Luo Y, Shi X. Method for preparing cellulose acetate/chitosan/carbon nanotubescomposite nanofiber with good biocompatibility. Faming Zhuanli Shenqing2011;102000363:20110406.

Shin YM, Hohman MM, Brenner MP, Rutledge GC. Electrospinning: a whipping fluid jetgenerates submicron polymer fibers. Appl Phys Lett 2001a;78:1149.

Shin YM, Hohman MM, Brenner MP, Rutledge GC. Experimental characterization ofelectrospinning: the electrically forced jet and instabilities. Polymer 2001b;42:9955.

Silveira JVW, Millás ALG, Tessarolli LF, Bittencourt E, Ago M, Rojas OJ. Production ofelectrospun cellulose acetate fiber mats as carriers of citronella essential oil. Ab-stracts of Papers, 239th ACS National Meeting, 305. United States: San Francisco,CA; 2012. [March 29].

SonWK, Youk JH, ParkWH. Antimicrobial cellulose acetate nanofibers containing silvernanoparticles. Carbohydr Polym 2006;65:430–4.

Sousa M, Brás AR, Veiga HI, Ferreira FC, de Pinho MN, Correia NT, Dionísio M. Dynamicalcharacterization of a cellulose acetate polysaccharide. J Phys Chem B 2010;114(34):10939–53.

Štengl V, Mariková M, Bakardjieva S, Šubrt J, Opluštil F, Olšanska M. Reaction of sulfurmustard gas, soman and agent VXwith nanosized anatase TiO2 and ferrihydrite. J ChemTechnol Biotechnol 2005;80(7):754–8.

Sud D, Mahajan G, Kaur MP. Agricultural waste material as potential adsorbent for se-questering heavy metal ions from aqueous solutions—a review. Bioresour Technol2008;99(14):6017–27.

437R. Konwarh et al. / Biotechnology Advances 31 (2013) 421–437

Sun X, Zhang L, Cao Z, Deng Y, Liu L, Fong H, Sun Y. Electrospun composite nanofiber fabricscontaining uniformly dispersed antimicrobial agents as an innovative type of polymericmaterials with superior antimicrobial efficacy. ACS Appl Mater Interfaces 2010;2(4):952–6.

Sundarrajan S, Ramakrishan S. Fabrication of functionalized nanofiber membranescontaining nanoparticles. J Nanosci Nanotechnol 2010;10(2):1139–47.

Suwantong O, Opanasopit P, Ruktanonchai U, Supaphol P. Electrospun cellulose acetatefiber mats containing curcumin and release characteristic of the herbal substance.Polymer 2007;48:7546–57.

Suwantong O, Ruktanonchai U, Supaphol P. In vitro biological evaluation of electrospuncellulose acetate fiber mats containing asiaticoside or curcumin. J Biomed MaterRes A 2010;94(4):1216–25.

Taepaiboon P, Rungsardthong U, Supaphol P. Vitamin-loaded electrospun cellulose ac-etate nanofiber mats as transdermal and dermal therapeutic agents for vitamin Aacid and vitamin E. Eur J Pharm Biopharm 2007;67:387.

Tam KH, Djurisic AB, Chan CMN, Xi YY, Tse CW, Leung YH, Chanm WK, Leng FCC, AuDWT. Antibacterial activity of ZnO nanorods prepared by a hydrothermal method.Thin Solid Films 2008;516:6167–74.

Tang C, Chen P, Liu H. Cocontinuous cellulose acetate/polyurethane composite nanofiberfabricated through electrospinning. Polym Eng Sci 2008;48(7):1296–303.

Theopisti C, Charalabos D. Biodegradable cellulose acetate nanofiber fabrication viaelectrospinning. J Nanosci Nanotechnol 2010;10(9):6226–33.

Thitiwongsawet P, Ouykul P, Khaoroppan A. 2,6-Dichloro-4-nitroaniline-loadedelectrospun cellulose acetate fiber mats and their release characteristics. AJCHE2010;10(2):41–7.

Tian Y, Wu M, Liu R, Li Y, Wang D, Tan J, Wue R, Huang Y. Electrospun membrane ofcellulose acetate for heavy metal ion adsorption in water treatment. CarbohydPolym 2011;83:743–8.

Tork A, Boudreault F, Roberge M, Ritcey AM, Lessard RA, Galstian TV. Photochromic be-havior of spiropyran in polymer matrices. Appl Optics 2001;40:1180–6.

Tsioptsias C, Sakellariou KG, Tsivintzelis I, Papadopoulou L, Panayiotou C. Preparationand characterization of cellulose acetate–Fe2O3 composite nanofibrous materials.Carbohydr Polym 2010;81(4):925–30.

Tungprapa S, Jangchud I, Supaphol P. Release characteristics of four model drugs fromdrug-loaded electrospun cellulose acetate fiber mats. Polymer 2007a;48:5030–41.

Tungprapa S, Puangparn T, Weerasombut M, Jangchud I, Fakum P, Semongkhol S,Meechaisue C, Supaphol P. Electrospun cellulose acetate fibers: effect of solventsystem on morphology and fiber diameter. Cellulose 2007b;14:563–75.

Tzeng JI, Chen MF, Chung HH, Cheng JT. Silymarin decreases connective tissue growthfactor to improve liver fibrosis in rats treated with carbon tetrachloride. PhytotherRes 2012. http://dx.doi.org/10.1002/ptr.4829.

Uddin MJ, Cesano F, Scarano D, Bonino F, Agostini G, Spoto G, Bordiga S, Zecchina A.Cotton textile fibres coated by Au/TiO2 films: synthesis, characterization and selfcleaning properties. J Photochem Photobiol A 2008;199:64–72.

Wang CB, Zhang WX. Synthesizing nanoscale iron particles for rapid and complete de-chlorination of TCE and PCBs. Environ Sci Technol 1997;31:2154–6.

Wang X, Kim Y-G, Drew C, Ku B-C, Kumar J, Samuelson LA. Electrostatic assembly ofconjugated polymer thin layers on electrospun nanofibrous membranes for bio-sensors. Nano Lett 2004;4:331–4.

Wang N, Chen H, Lin L, Zhao Y, Cao X, Song Y, Jiang L. Multicomponent phase changemicrofibers prepared by temperature control multifluidic electrospinning. MacromolRapid Commun 2010;31:1622–7.

Wildman REC. Handbook of nutraceuticals and functional foods. Boca Raton, FL, USA:CRC Press; 2001.

Wongsasulak S, Patapeejumruswong M, Weiss J, Supaphol P, Yoovidhya T.Electrospinning of food-grade nanofibers from cellulose acetate and egg albumenblends. J Food Eng 2010;98:370–6.

Wu X-M, White CJB, Zhu L-M, Chatterton NP, Yu D-G. Ester prodrug-loaded electrospuncellulose acetate fiber mats as transdermal drug delivery systems. J Mater Sci MaterMed 2010;21:2403–11.

Xiangyu Y, Gele A, Xuesong Z. Preparation of core-shell structured technicallignin/cellulose acetate fibers by Co-electrospinning Pacifichem 2010. InternationalChemical Congress of Pacific Basin Societies, 297. United States: Honolulu, HI; 2010.[December 15–20].

Xiao S, Wu S, Shen M, Guo R, Huang Q, Wang S, Shi X. Polyelectrolytemultilayer-assisted immobilization of zero-valent iron nanoparticles onto polymernanofibers for potential environmental applications. ACS Appl Mater Interfaces2009;1(12):2848–55.

Yao JN, Hashimoto K, Fujishima A. Photochromism induced in an electrolyticallypretreated MoO3 thin film by visible light. Nature 1992;355:624–6.

Yoo HS, Kim TG, Park TG. Surface-functionalized electrospun nanofibers for tissueengineering and drug delivery. Adv Drug Deliv Rev 2009;61:1033–42.

Yu D-G, Yu J-H, Chen L, Williams GR, Wang X. Modified coaxial electrospinning for thepreparation of high-quality ketoprofen-loaded cellulose acetatenanofibers.Carbohydr Polym 2012;90(2):1016–23.

Yuvaraj D, Kaushik R, Narasimha RK. Optical, field-emission, and antimicrobial propertiesof ZnO nanostructured films deposited at room temperature by activated evapora-tion. ACS Appl Mater Interfaces 2010;2(4):1019–24.

Zhang L, Hsieh Y-L. Ultrafine cellulose acetate fibers with nanoscale structural features.J Nanosci Nanotechnol 2008;8(9):4461–9.

Zhang L, Hsieh Y-L. Carbon nanofibers with nanoporosity and hollow channels from binarypolyacrylonitrile systems. Eur Polym J 2009;45(1):47–56.

Zhang L, Menkhaus TJ, Fong H. Fabrication and bioseparation studies of adsorptivemembranes/felts made from electrospun cellulose acetate nanofibers. J MembrSci 2008;319(1+2):176–84.

Zhao D, Sun L, Lv L, Li J. Preparation of cellulose acetate ultra-fine fibers containingquasi-spherical gold nanoparticles by electrospinning method. Adv Mat Res2012a;391–392:400–3.

Zhao D, Sun L, Wang M, Li J. Fabrication and characterization of cellulose acetateultrafine fibers containing CdTe quantum dots by electrospinning. Appl MechMater 2012b;174–177:140–3.

Zhou W, He J, Cui S, Gao W. Preparation of electrospun silk fibroin/cellulose acetateblend nanofibers and their applications to heavy metal ions adsorption. FiberPolym 2011a;12(4):431–7.

Zhou W, He J, Du S, Cui S, Gao W. Electrospun silk fibroin/cellulose acetate blendnanofibres: structure and properties. Iran Polym J 2011b;20(5):389–97.

Zhu L, Zhang H, Cao M, Liu J, Nie H. Method for manufacture of modified electrospunnylon/cellulose acetate nanofiber membrane with good mechanical strength. FamingZhuanli Shenqing Gongkai Shuomingshu 2009;101538775:20090923.