Aplicações Avançadas em Nanofibras

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<p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 1/50</p><p>Polímeros (Basileia). 2021 novembro; 13(21): 3746.</p><p>Published online 2021 Oct 29. doi: 10.3390/polym13213746</p><p>PMCID: PMC8587893</p><p>PMID: 34771302</p><p>A Review on Electrospun Nanofibers Based Advanced Applications: From Health</p><p>Care to Energy Devices</p><p>Vundrala Sumedha Reddy, Yilong Tian, Chuanqi Zhang, Zhen Ye, Kallol Roy, Amutha Chinnappan,</p><p>Seeram Ramakrishna, Wei Liu, and Rituparna Ghosh</p><p>Lilia Sabantina, Academic Editor</p><p>Abstract</p><p>Electrospun nano�ibers have been exploited in multidisciplinary �ields with numerous applica-</p><p>tions for decades. Owing to their interconnected ultra�ine �ibrous structure, high surface-to-</p><p>volume ratio, tortuosity, permeability, and miniaturization ability along with the bene�its of</p><p>their lightweight, porous nano�ibrous structure, they have been extensively utilized in various</p><p>research �ields for decades. Electrospun nano�iber technologies have paved unprecedented</p><p>advancements with new innovations and discoveries in several �ields of application including</p><p>energy devices and biomedical and environmental appliances. This review article focused on</p><p>providing a comprehensive overview related to the recent advancements in health care and</p><p>energy devices while emphasizing on the importance and uniqueness of utilizing nano�ibers. A</p><p>brief description regarding the effect of electrospinning techniques, setup modi�ications, and</p><p>parameters optimization on the nano�iber morphology was also provided. The article is con-</p><p>cluded with a short discussion on current research challenges and future perspectives.</p><p>Keywords:	nano�ibers, electrospinning, applications, health care, energy devices</p><p>1. Introduction</p><p>The fourth industrial revolution has remodeled various technological domains including</p><p>nanotechnology, biotechnology, new materials, arti�icial intelligence, and human-machine inter-</p><p>faces. This resulted in the conjugation of nanotechnology with medicine and has also driven a</p><p>new wave into the energy sector [1,2,3]. The effect of this emergence has been evidently noti-</p><p>ced in the past two years during the period of COVID-19, when there was a smooth overall out-</p><p>door-to-indoor transition through advanced portable miniaturized technologies. Advancement</p><p>in these different aspects has resulted in the overall ampli�ication of global market value, pictu-</p><p>rized in Figure 1. In health care [4], the global market value is anticipated to increase from</p><p>397.5 to 602.1 billion USD in the timeline from 2017 to 2025 (Figure 1a), where the global</p><p>energy devices market [5] has projected a 451.29 to 908.49 billion USD enhancement from</p><p>2016 to 2022 (Figure 1b) and the global smart fabrics market [6] is estimated to increase up</p><p>to 5.93 from 1.8 billion USD from 2018 to 2025 (Figure 1c).</p><p>1 1,2 1 1 3 1</p><p>1,* 4,* 1,*</p><p>https://doi.org/10.3390%2Fpolym13213746</p><p>https://pubmed.ncbi.nlm.nih.gov/34771302</p><p>https://pubmed.ncbi.nlm.nih.gov/?term=Reddy%20VS%5BAuthor%5D</p><p>https://pubmed.ncbi.nlm.nih.gov/?term=Tian%20Y%5BAuthor%5D</p><p>https://pubmed.ncbi.nlm.nih.gov/?term=Zhang%20C%5BAuthor%5D</p><p>https://pubmed.ncbi.nlm.nih.gov/?term=Ye%20Z%5BAuthor%5D</p><p>https://pubmed.ncbi.nlm.nih.gov/?term=Roy%20K%5BAuthor%5D</p><p>https://pubmed.ncbi.nlm.nih.gov/?term=Chinnappan%20A%5BAuthor%5D</p><p>https://pubmed.ncbi.nlm.nih.gov/?term=Ramakrishna%20S%5BAuthor%5D</p><p>https://pubmed.ncbi.nlm.nih.gov/?term=Liu%20W%5BAuthor%5D</p><p>https://pubmed.ncbi.nlm.nih.gov/?term=Ghosh%20R%5BAuthor%5D</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f001/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f001/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f001/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f001/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 2/50</p><p>Figure 1</p><p>Statistics of (a) the global health care market (b) the global energy devices market and (c) the global smart fa-</p><p>brics market.</p><p>The ability to make large differences with micro/nano scale materials has been realized th-</p><p>rough nanotechnology [7,8]. The materials in the nanoscale range are a rapidly developing do-</p><p>main that has made a huge contribution towards revolutionizing these technologies [9,10,11].</p><p>Even though there are various nanostructured materials like nanoparticles, nanodots, na-</p><p>nosheets, nanorods, nano�lowers, and etc., nano�ibers [12], with their unique fabrication</p><p>methods and tunable properties, have become a much-explored area for various applications</p><p>in the �ields of sensors [13], tissue engineering [14], drug delivery [15], wound healing [16],</p><p>energy devices [17], �iltration [18], distillation [19], the environment, etc.</p><p>Owing to their novel physical and chemical properties in providing high speci�ic surface area,</p><p>large surface-to-volume ratio, tunable porosity, and the ability of desired chemical functionali-</p><p>zation, they are competent enough to overcome many limitations faced in their corresponding</p><p>macroscales [20]. There are several fabrication techniques such as thermal-induced phase se-</p><p>paration [21], self-assembly [22], template synthesis [23], and electrospinning for synthesizing</p><p>nano�ibers. However, among these, the electrospinning technique is the most favorable choice</p><p>due to the formulation into 2D and 3D structures as well as its simple, continuous, straight-</p><p>forward, rapid, and cost-effective process of manufacturing nano�ibers [24]. Electrospinning is</p><p>the most ef�icient way to prepare composite �ibers with synergistic characteristics for new ap-</p><p>plications through blending multiple polymers with individual functionalities in the solution</p><p>phase [25].</p><p>Branched-out applications of the nano�ibrous material are presented in Figure 2. Major contri-</p><p>butions in the advancement of technologies have been observed in health care applications</p><p>[26], mainly in the aspects of biosensing [27], tissue engineering [28], wound dressing [29],</p><p>and drug delivery [30]. In the biomedical �ield, it has been recognized that the human anatomy</p><p>https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=8587893_polymers-13-03746-g001.jpg</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f001/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f002/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 3/50</p><p>of organs and tissues like skin, bones, collagen, cartilage, etc. can be imitated or resembled by</p><p>tuning nano�iber material [31]. The large surface area is extensively exploited in these studies</p><p>in enhancing adhesion to cells, proteins, and drugs when compared with the bulk materials,</p><p>which gives nano�ibers an edge.</p><p>Figure 2</p><p>Various applications of electrospun nano�ibrous materials. Health care applications [26]: biosensor [27], tis-</p><p>sue engineering [28], wound dressing [29], drug delivery [30]; energy devices [32]: battery [33], supercapa-</p><p>citor [34], solar cell [35], transistor [36], nanogenerator [37]; miscellaneous applications: fabric technology</p><p>[39], catalysis [40], fuel cell [41], and �iltration [42].</p><p>Shredding some light on the environmental deterioration, climate change, and depleting fossil</p><p>fuels, the dire importance of developing renewable and rechargeable energy devices is un-</p><p>derstood. Here, the nano�ibers have been broadly utilized in various types of energy devices</p><p>[32] including batteries [33], supercapacitors [34], solar cells [35], transistors [36], nanogene-</p><p>rators [37], etc. The use of nano�ibers in energy conversion and storage devices has</p><p>signi�icantly drawn</p><p>(PVA)-melatonin (MEL)/chitosan-</p><p>polycaprolactone three-layer nano�iber</p><p>The three-layer wound</p><p>dressing reduced burst release</p><p>(45%) and led to a sustained</p><p>release of melatonin.</p><p>Wound</p><p>dressing</p><p>[157]</p><p>Starch/AgNPs composite</p><p>nano�iber mats altered Wound</p><p>3.2. Energy Devices</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 25/50</p><p>The increase in energy demand for sustained economic growth with the simultaneous deple-</p><p>tion of fossil fuels and emerging renewable energy is growing rapidly. Nowadays, innovation</p><p>and sustenance of such renewable energy technologies/devices has become of dire impor-</p><p>tance. Some of the renewable energy sources comprise solar, wind, tidal, geothermal, etc. In</p><p>energy management and usage, various issues like maximization, prolonged dependence,</p><p>stability, etc. have paved the scope for energy storage technologies like fuel cells, solar cells,</p><p>batteries, nanogenerators, and supercapacitors, etc. In this �ield of research, nano�ibers</p><p>synthesized through electrospinning techniques have come provide unique properties such as</p><p>high surface areas and porosities, which are widely exploited for energy conversion, harves-</p><p>ting, and storage. Recent studies on nano�iber-based energy storage devices are discussed in</p><p>this section [17,103,104,105].</p><p>3.2.1. Batteries and Supercapacitors Batteries are power sources that are either rechargeable</p><p>or single usage. Some of their essential requirements include a porous, sponge-type structure</p><p>of electrodes and separators to enable high discharge current capacity and allow the free ex-</p><p>change of ions (high ion conductivity and permeability) while ef�iciently preventing short cir-</p><p>cuits, respectively. Along with ful�illing the above requisites, nano�ibers can also provide me-</p><p>chanical strength and high electrochemical stability with improved cycle life through well inter-</p><p>connected porous membranes [163,164]. Some of the current research works in battery appli-</p><p>cations are reported below.</p><p>In battery technologies, Lithium-ion batteries (LIBs) are the most researched area due to their</p><p>high volumetric, gravimetric energy density with light weight and good shape versatility, which</p><p>has led to various miniaturized applications in electrotonic as well as electrical appliances.</p><p>However, achieving high power capability along with high energy density along the way re-</p><p>mains a challenge. Here, electrospun nano�ibers are implemented to overcome these dif�icul-</p><p>ties by enhancing electric and ionic conductivities of LIBs through utilizing high speci�ic surface</p><p>area, porosity, controllable �iber diameter, and well interconnected porous structure. Moreo-</p><p>ver, they can be functionalized to have controlling ability over properties like electrolyte</p><p>af�inity, pore size, and thermal stability to achieve enhanced cell performance [165].</p><p>Electrospun aramid �ibers have been utilized in batteries as solid-state electrolyte materials to</p><p>achieve high ionic conductivity along with mechanical stability, which are the prerequisites for</p><p>solid-state LIBs. In their latest work, Liu et al. [166] used aramid (ANFs)</p><p>nano�ibers/polyethylene oxide (PEO) Lithium bis(tri�luoromethanesulfonyl)imide (TFSI) as so-</p><p>lid-state electrolyte to fabricate LIB. The composite material consisting of ANFs and</p><p>polyparaphenylene terephthalamide (PPTA) molecules possess characteristics like large aspect</p><p>ratio, high mechanical strength thermo-decomposition temperature, abundant amide groups,</p><p>light weight, low electrical conductivity, and high chemical inertness, which enhances material</p><p>strength. On the other hand, soft PEO polymer was used as electrolyte material to dissolve Li</p><p>salts. Here ANFs were utilized as nano additive organic �illers in the composite electrolyte de-</p><p>sign achieved through hydrogen-bond interactions between ANFs, PEO chains, and TFSI ani-</p><p>ons. These, in turn, facilitated prolonging ion transport paths and provided a superior</p><p>conductivity of 8.8 × 10 S cm and cycling stability of 135 mAh g after 100 cycles at 0.4 C.</p><p>Comprehensive upgradation of the electrolyte was observed through obtaining higher ion</p><p>conductivity, mechanical and electrochemical stabilities, and interfacial resistance against Li</p><p>dendrites. For portable, wearable electronics, development of �lexible and foldable LIBs that</p><p>provide shorter charge and longer discharge time have received increasing attention. Traditio-</p><p>nal LIBs usually lack in the area of �lexibility due to their weight and rigid built-up characteris-</p><p>−5 −1 −1</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 26/50</p><p>tics. Hence, to address such an issue, a study involving free-standing and foldable vanadium</p><p>oxide/multichannel carbon nano�ibers (V O /MCCNFs) composites prepared via electrospin-</p><p>ning (Figure 8a) was carried out. Usually, in the traditional slurry-casting electrode preparation</p><p>at high mass loading, materials are easily peeled off from the current collector after several en-</p><p>foldments, which results in rapid capacity decay. This issue is resolved through using �lexible</p><p>electrodes, which possess low cost, foldability, and lightweight features. In this study, a �lexible</p><p>structure formed by loading V O particles on MCCNFs was used that provided high energy</p><p>density, superior rate performance, as well as long cycling life. Here, 1D nano�ibers multichan-</p><p>nel was designed through electrospinning to buffer the volume change, reduce the transport</p><p>length of Lithium ions, and improve the matrix conductivity. These free-standing V O /MCCNFs</p><p>deliver high capacity, excellent rate capability, and ultralong lifespan, along with the bene�its</p><p>like light weight, high-energy density, and remarkable cycling performance. The electrodes tes-</p><p>ted delivered superior capacity of 881.1 mAh g at 0.1 A g and 487.8 mAh g at 5 A g af-</p><p>ter 240 cycles and 5000 cycles with 0.00323% decay rate [167].</p><p>Figure 8</p><p>(a) Schematics on formation process of V O /MCCNFs composites; free-standing �ilms prepared by electros-</p><p>pinning; displaying �lexibility and 180° folding �ilms [167]. (b) Illustration of the device used for water detec-</p><p>tion, as well as the Mg–water reactions and ion transportation happening in the CNF porous structure; pulse</p><p>signals in response to relative humidity changes by the human breath detected by the device [169]. (c) Sche-</p><p>matic of the stepwise fabrication process of NiGa S /Ni@CNF; electrochemical characteristics of �lexible su-</p><p>percapacitors, CV curves with varying curvature radii (mm) with liquid and solid electrolyte [173].</p><p>2 3</p><p>2 3</p><p>2 3</p><p>−1 −1 −1 −1</p><p>2 3</p><p>2 4</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f008/</p><p>https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=8587893_polymers-13-03746-g008.jpg</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f008/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 27/50</p><p>LIBs have pioneered battery technologies for decades with their high performance. However,</p><p>there are still disadvantages such as toxicity and safety hazards due to their highly reactive</p><p>properties and thermal runaway caused by dendrite formation, which has triggered research</p><p>for mono and multivalent metal-ion battery systems. In past few years, magnesium-ion batte-</p><p>ries (MIBs) have exhibited promising qualities due to the abundance in availability of magne-</p><p>sium and its ability to provide a volumetric capacity of 3832 mA h cm , which is twice as much</p><p>of lithium. In their recent work, Diem and coworkers fabricated a hybrid magnesium–lithium-</p><p>ion battery (MLIB) using a binder-free</p><p>and self-supporting V O nano�iber-based cathode with</p><p>magnesium anode and dual-salt electrolyte containing both Mg and Li [168]. V O is a pro-</p><p>mising intercalation compound, as it can provide high storage capacities and energy densities</p><p>owing to its redox chemistry. The presence of VO bilayer chains makes it a suitable cathode</p><p>material for MLIBs. The space between the layers contain water molecules, which provides</p><p>large vacancy to host intercalating ions and can facilitate ion insertion into intercalation sites.</p><p>Here, V O nano�iber cathode helped in achieving high energy densities by providing high in-</p><p>tercalation potential. In this rechargeable electrochemical storage system, the cathode provi-</p><p>ded a high operating voltage of up to 1.5 V vs. Mg/Mg while achieving storage capacities of</p><p>around 386 mAh g , complemented with an energy density of 280 W h kg and good cycling</p><p>stability of 200 mA g over 500 cycles.</p><p>Another hybrid battery study on a hygroelectric generator was carried out by Feng et al. [169]</p><p>using an oxidized carbon nano�iber cathode and Mg anode based on the enhanced capacitive</p><p>discharging effect. The concept of a water/moisture-induced hygroelectric effect depends on</p><p>direct contact between magnesium alloy and oxidized carbon nano�ibers in the presence of</p><p>water (Figure 8b). Here, the CNF network acted as a good water-absorbing electrode. The re-</p><p>duction potential of Mg alloy was able to tune the oxidation of CNF and output voltage was</p><p>made to exceed the limit while still generating a high current density.</p><p>The device could generate an open-circuit voltage up to 2.65 V and average peak short-circuit</p><p>current density of ~6 mA/cm when in contact with liquid water, hence making it a potential</p><p>candidate in water or vapor leakage detection, portable energy source, humidity sensors, etc.</p><p>The �iber network in this study acted as a good water-absorbing material and could produce a</p><p>high current density exceeding the reduction potential of magnesium by tuning the oxidation</p><p>of the carbon nano�iber.</p><p>Other than Li and Mg batteries, Zn is another transition metal which has been highly explored</p><p>in battery research for its high theoretical gravimetric energy (1086 Wh kg ), easy conversion</p><p>and storage, abundancy in nature, low cost, and environmental friendliness. Zang et al. [170]</p><p>engineered NiO/NiCo O porous nano�ibers by electrospinning to use as bifunctional catalysts</p><p>in the rechargeable Zinc air battery. NiO has been proven to be an ideal electrocatalyst in</p><p>oxygen evolution reaction (OER)/oxygen reduction reaction (ORR) due to its special e orbi-</p><p>tals, as the surface of nanoscale NiO is oxidized easily to active Ni species. On the other hand,</p><p>spinel structured NiCo O has also been known as a promising OER, ORR electrocatalyst, as the</p><p>cobalt and nickel ions can introduce various functions within the structure. In this engineered</p><p>structure of NiO/NiCo O , chemical bonds that form at the interface facilitate a higher charge-</p><p>transfer rate. In parallel, the heterostructure also promotes the intrinsic activity of OER/ORR</p><p>through exposure of more electrocatalytic active sites. As a result, the interface engineering of</p><p>NiO/NiCo O with numerous mesopores synergistically provides suf�icient oxygen transport,</p><p>satisfactory intrinsic activity, and abundant electrocatalyst’ active sites. Here, NiO/NiCo O po-</p><p>rous nano�ibers contributed to enhancing electron transfer rate and promoting the intrinsic</p><p>−3</p><p>2 5</p><p>2+ +</p><p>2 5</p><p>5</p><p>2 5</p><p>2+</p><p>−1 −1</p><p>−1</p><p>2</p><p>−1</p><p>2 4</p><p>g</p><p>3+</p><p>2 4</p><p>2 4</p><p>2 4</p><p>2 4</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f008/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 28/50</p><p>activity through providing exposure to more electrocatalytic active sites. The synthesized</p><p>catalyst exhibited superior electrocatalytic performance, lower overpotential of 357 mV at 10</p><p>mA cm , half-wave potential of 0.73 V, speci�ic capacity of 814.4 mA h g , and cycling stability</p><p>of 175 h.</p><p>Apart from the batteries, supercapacitors are another type of electrochemical energy storage</p><p>devices that can store and release energy by reversible adsorption and desorption of ions at</p><p>the electrode-electrolytes interface. High power density, rapid charge/discharge rate, and cycle</p><p>stability are some of the key requisites of supercapacitors, which are supported by large sur-</p><p>face area and high porosity of nano�iber material. The �ibrous nanostructures surface</p><p>morphology with high surface-to-volume ratio aids in increasing the energy storage capability</p><p>by increasing interfacial activity between electrode and electrolyte [171,172]. A few of the la-</p><p>test research works in the �ield of nanogenerators are summarized here.</p><p>The development of supercapacitors with high energy density and rate capability is extensively</p><p>explored for energy storage applications in electric vehicles and in wearable portable electro-</p><p>nic devices. However, the conventional supercapacitors lack �lexibility. To address this issue,</p><p>Kim et al. [173] fabricated a metallized nickel platted carbon nano�iber (Ni@CNF) decorated</p><p>with 2D Nickel Gallium sul�ide (NiGa S ) nanosheets. Here, NiGa S nanosheets improved the</p><p>electrochemical activity by promoting electrolyte-to-electrode diffusion. Along with this, supe-</p><p>rior electrical conductivity of the Ni@CNF provided electrochemical stability and also enhan-</p><p>ced charge transfer that occurs in the electrode (Figure 8a). These nano�ibers enhanced the</p><p>pseudo capacitance and energy density of the nanosheets, whereas nanosheets contributed</p><p>towards improving the energy storage capability and electrochemical activity. The device re-</p><p>ported the highest speci�ic capacitance at 488 F g with a potential window of 1.1 V and cur-</p><p>rent rate of 0.5 A g , long-term stability with capacitance retention 109% after 20,000 cycles,</p><p>and �lexibility effect on the cyclic voltammetry performance was tested by 2000 bending cycles,</p><p>yielding favorable results. In another recent study, Jeong et al. [174] developed a template-less</p><p>hierarchical porous carbon nano�iber/manganese oxide (MnO )-derived electrospun</p><p>polyacrylonitrile/cyclodextrin (CD) composite PMnCD(β) using β-CD phase, which exhibited a</p><p>hierarchical porous structure. Hybrids of nano-sized MnO and carbon nano�ibers have been</p><p>declared as suitable candidates for supercapacitor electrodes, as they simultaneously exhibit</p><p>high pseudo capacity and excellent electronic conductivity. The as fabricated PMnCD(β) elec-</p><p>trode showed a large speci�ic surface area for accumulation of ions and fast ion diffusion due</p><p>to the mesopores and nitrogen groups. The β phase of CD nano�ibers exhibited a hierarchical</p><p>porous structure with a large speci�ic surface area of 499 m g , and 0.32 cm g total pore</p><p>volume, that assisted in accumulation of hydrated molecules for double-layer formation by im-</p><p>proving adsorption ef�iciency. Here. the electrode reported a maximum energy density of</p><p>25.3–16.0 Whkg within the power density range of 400–10,000 Wkg , high speci�ic capaci-</p><p>tance of 228 Fg at 1 mAcm , and excellent cycling stability of 94% after 10,000 cycles.</p><p>Nowadays, to further enhance the speci�ic surface area, structural uniformity, porosity,</p><p>functionality and diverse topology of supercapacitors, metal–organic frameworks (MOFs), and</p><p>their derivatives are being integrated to the electrospun �ibers network. Recently, Mukhiya and</p><p>coworkers developed a 3D Co O /N-CNTs@CNFs for supercapacitors, exhibiting a promising</p><p>performance through self-templated MOF-synthesized onto carbonized electrospun carbon na-</p><p>no�ibers (CNF) mat. The composite supercapacitor exhibited a high speci�ic capacity of 238 mA</p><p>h g at 1 A g with a long lifespan and high rate capability. The assembled asymmetric super-</p><p>capacitor could deliver 52.9 Whkg speci�ic energy at a speci�ic power of 873.5 Wkg outs-</p><p>−2 −1</p><p>2 4 2 4</p><p>−1</p><p>−1</p><p>2</p><p>2</p><p>2 −1 3 −1</p><p>−1 −1</p><p>−1 −2</p><p>3 4</p><p>−1 −1</p><p>−1 −1</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f008/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 29/50</p><p>tanding lifetime (90.1% after 10,000 cycles) [175]. Apart from these, all-solid-state supercapa-</p><p>citors are becoming popular for their various advantages in terms of structural stability, opera-</p><p>tional safety, lightweight properties, and eco friendliness while also facilitating leakage preven-</p><p>tion compared with the liquid electrolyte-based supercapacitors. By utilizing �iber-�iber inter-</p><p>connections, high speci�ic surface area, and hierarchical pore structure of electrospun carbon</p><p>nano�iber mats (ECNFMs), Wang and coworkers recently developed a high-performance all-so-</p><p>lid-state supercapacitor. Here, ECNFMs were prepared by electrospinning of PAN and novolac</p><p>resin (NOC) solution blend, where PAN was used as carbon precursor and NOC acted as a sa-</p><p>cri�icial agent contributing towards pore-generation. The highest obtained speci�ic surface area</p><p>value was 1468 m g when ECNFMs were carbonized at 1000 °C. A symmetrical supercapaci-</p><p>tor device was prepared by sandwiching PVA/(Sulfuric acid) H SO hydrogel within two frees-</p><p>tanding ECNFMs. The device exhibited a high speci�ic capacitance of ~99.72% along with excel-</p><p>lent capacitance retention of ~320 mF cm at 0.25 mA cm after 10,000 charge/discharge</p><p>cycles. Along with that, a large energy density of ~11.1 μWh cm was obtained for input</p><p>power density of 500 mW m [176].</p><p>In another study, Singh et al. fabricated all-solid-state supercapacitors by kraft lignin-derived</p><p>heat-treated carbon nano�ibers. Although most of the studies use synthetic PAN polymer, its</p><p>higher cost, non-renewable nature, and tendency to release toxic gases like HCN during heat</p><p>treatment have promoted the usage of some renewable green precursors like Lignin, cellulose,</p><p>etc. for synthesizing CNF. In this study, Lignin was selected for its abundancy in nature, non-</p><p>toxicity, higher aromatic structure carbon content, and renewability. Higher speci�ic capaci-</p><p>tance 196.63 F/g was achieved for 1 A/g current density. For direct comparison, the device</p><p>was tested in both aqueous (using 1 M H SO ) as well as polymer gel electrolyte (using PVA-</p><p>1M H SO hydrogel). The solid-state electrolyte device could operate at higher voltages (exhi-</p><p>biting potential window of 0–2 V) compared with the aqueous electrolyte (where the potential</p><p>window ranged within 0–1.6 V). Even after 10,000 cycles, the device exhibited 62.6 Wh/kg</p><p>energy density and 1.25 kW/kg power density with 99.5% ef�iciency, providing futuristic</p><p>energy storage applications of carbon nano�ibers-based solid-state electrolyte [177]. Role of</p><p>different nano�iber materials used in various type of batteries and supercapacitor applications</p><p>are summarized in Table 5.</p><p>2 −1</p><p>2 4</p><p>−2 −2</p><p>−2</p><p>−2</p><p>2 4</p><p>2 4</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/table/polymers-13-03746-t005/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 30/50</p><p>Table 5</p><p>Role of nano�iber materials in various battery and super capacitor applications.</p><p>Materials Property	and	Role Application Ref.</p><p>ANF/PEO-LiTFSI CPE �ilms</p><p>Provided large aspect ratio and high</p><p>mechanical strength, and</p><p>conductivity. The CPEs also</p><p>displayed greatly enhanced</p><p>electrochemical, mechanical and</p><p>thermal stabilities with superior rate</p><p>performance and cycling stability</p><p>Li-ion battery [166]</p><p>Vanadium oxide/multichannel</p><p>carbon nano�ibers</p><p>Exhibited unprecedented</p><p>electrochemical rate performance,</p><p>long cyclability</p><p>Li-ion battery [167]</p><p>Zeolitic imidazolate framework-</p><p>67/cellulose nano�ibers</p><p>Displayed improved pore structure,</p><p>excellent thermal stability, lower</p><p>thermal shrinkage, and better surface</p><p>wettability. Lithium-ion batteries</p><p>assembled with ZIF-67@CNF</p><p>membrane showed higher cycling</p><p>performance and rate capability than</p><p>the other membranes</p><p>Li-ion battery [178]</p><p>Binder-free and self-supporting</p><p>V O nano�iber</p><p>Cathode materials: high storage</p><p>capacities, good cycling stability</p><p>while holding structural integrity</p><p>Magnesium–</p><p>lithium-ion hybrid</p><p>battery</p><p>[168]</p><p>Carbon nano�ibers (CNF)</p><p>The oxidized CNF was shown to</p><p>absorb water/moisture and became</p><p>reduced, leading to a capacitive</p><p>discharging effect to provide</p><p>enhanced signal amplitude and</p><p>sensitivity</p><p>Magnesium</p><p>battery</p><p>[169]</p><p>Porous NiO/NiCo O nano�ibers</p><p>with</p><p>Provided �lexibility and long cycling</p><p>life (14 h)</p><p>Zinc-air battery [170]</p><p>Nitrogen-doped porous carbon</p><p>@Carbon nano�iber aerogels</p><p>Exhibited peak density of 96 mW</p><p>cm and stable charge discharge</p><p>durability</p><p>Zinc-air battery [179]</p><p>Vanadate nano�iber crystal</p><p>structure/poly(3,4-ethylene</p><p>Intercalation of the conducting</p><p>polymer increased electron pathway,</p><p>in turn increasing number of active</p><p>sites inside the vanadate and Zinc ion battery [180]</p><p>2 5</p><p>2 4</p><p>−2</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 31/50</p><p>3.2.2. Nanogenerators and Solar Cells The nanogenerator is a portable energy-harvesting</p><p>technology that converts small mechanical or thermal energy changes and produces electricity.</p><p>Typically, nanogenerators are of three kinds based on the mechanism involved: piezoelectric</p><p>(generating electric charge in response to applied mechanical deformation) [183], triboelec-</p><p>tric, which is a combination of triboelectri�ication (the phenomenon of the certain class of ma-</p><p>terials to become electrically charged when brought in contact with their conjugate material</p><p>with opposite tribopolarity) and electrostatic induction [184], and pyroelectric (generating</p><p>electric charge in response to the changing thermal energy) [185]. Among these, triboelectric</p><p>nanogenerators (TENGs) are being noticed for their high output voltage, simpli�ied con�igura-</p><p>tion, lightweight properties, cost-effective fabrication, �lexible operation, etc. towards which na-</p><p>no�ibers play a crucial role. Hence, they have been intensively explored in the past few years.</p><p>To produce a scalable energy harvester for human motion monitoring and powering various</p><p>light-emitting diode, Huang and coworkers used a simple one-step-electrospinning technique.</p><p>Here, TENG was developed by electrospinning ethyl cellulose/polyamide 6 and poly(vinylidene</p><p>�luoride) (PVDF) polymers (Figure 9A). In this study, ethyl cellulose (EC)/polyamide 6 (PA6)</p><p>nano�iber served as a triboelectric positive material whereas PVDF incorporated with MXene</p><p>sheet acted as a negative material. MXene has strong electronegativity and electrical</p><p>conductivity, which boosts the triboelectric negativity of the PVDF nano�ibers which, in turn,</p><p>effectively improves the output of the TENG. EC has higher triboelectric positivity compared</p><p>with PA6, but the tensile strength of EC nano�iber mats increases when it is blended with PA6,</p><p>making EC/PA6 composite nano�iber mats a suitable candidate. The assembled TENG displayed</p><p>stability, durability, and good output performance with peak power density of 290 mW/m at a</p><p>100 MΩ load resistance [186]. For composite nano�iber-based electrical devices, it has been</p><p>reported that the �iber production technique also plays a crucial role in controlling their elec-</p><p>trical as well as surface charge density. In their recent work, Kim and team developed</p><p>polyimide/poly(vinylidene �luoride-co-tri�luoroethylene) (PI/PVDF-TrFE) composite nano�iber</p><p>membranes using single, conjugated, and multi-nozzle electrospinning systems [187]. Both PI</p><p>and PVDF-TrFE have excellent triboelectric negativity as well as high dielectric constants. Here,</p><p>combining PI as a transition layer with the PVDF-TrFE polymer contributed synergistically</p><p>towards the TENGs performance. They reported</p><p>that among the three types of systems, �ibers</p><p>obtained through the multi-nozzle technique exhibited the highest surface potential due to</p><p>their thinner �iber diameter. During multi-nozzle electrospinning, PI nano�ibers were placed</p><p>adjacent to the PVDF-TrFE, forming well-developed crystalline structure resulting in a signi�i-</p><p>cant improvement in the electrical performances (obtaining stable energy harvesting up to</p><p>10,000 cycles of loading, with the ability to illuminate 117 light-emitting diodes) due to its high</p><p>surface area. It was noted that the multi-nozzle setup delivered 364 V output voltage, 17.2 μA</p><p>short-circuit current, and 29.72 nC transferred charge with power density of 2.56 W/m at a</p><p>load resistance of 100 MΩ, which turned out to be about seven times greater than other nano-</p><p>�ibers obtained from other setups.</p><p>2</p><p>2</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f009/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 32/50</p><p>Figure 9</p><p>(A) Schematic of fabrication process, working mechanism, voltage, and current signals of TENG [186]. (B) Il-</p><p>lustration of electrospinning system; SEM images and diameter distributions of PVDF �iber, (a) Short-circuit</p><p>current of PENG with 2 wt% rGO under bending conditions. (b) One cycle short circuit current generated</p><p>from the PENG with 2 wt% rGO. The inset shows the PENG with 2 wt% rGO mounted on the wrist with a ben-</p><p>ding and release gesture. (c) Short-circuit current of PENG with 2 wt% rGO under the condition of wind speed</p><p>as 8 m/s. The illustration shows that the hair dryer continues to blow PENG. (d) Load resistance dependence</p><p>of the output voltage and output power of the 2% rGO/PVDF PENG pressed at 2 Hz frequency. (e) Schematic</p><p>illustration of recti�ier circuit. (f) Before lighting the bulb. (g) The bulb was lighted [190].</p><p>Coaxial electrospinning is a technique mostly used for simultaneous electrospinning of soluti-</p><p>ons with poor dispersion and incompatibility. Zhang and group constructed a high-output-per-</p><p>formance nano�iber TENG device comprising inorganic/organic hybrid materials to achieve</p><p>synergic dielectric and dispersity modulation [188]. In this work, polydimethylsiloxane and ba-</p><p>rium titanate nanoparticles (BT NPs) were combined as the core and PVDF as shell layer of the</p><p>coaxial nano�iber during the electrospinning process. BT NPs is a kind of inorganic piezoelec-</p><p>tric ceramic that has excellent dielectric properties. It can effectively enhance the permittivity</p><p>and surface charge density of corresponding triboelectric materials. PDMS is a widely used</p><p>ideal tribo-negative material, and due to its good charge retention capability and presence of</p><p>silicon hydroxyl end groups it possesses a better compatibility with BT than PVDF. The optimi-</p><p>zed device exhibits a high output voltage of 1020 V, a current of 29 μA, and a maximum power</p><p>density of 2.2 W/m under a 30 MΩ load resistance. Due to their high energy conversion</p><p>ef�iciency and ease of implementation, piezoelectric nanogenerators are extensively exploited</p><p>as energy harvesting devices [189]. Designing piezoelectric devices with composite nano�iber</p><p>is another popularly researched area in the nanogenerator �ield. Recently, Yang et al. [190] fa-</p><p>bricated one of such piezoelectric devices using GO/PVDF electrospun nano�ibers (Figure 9B).</p><p>In PVDF polymer, β phase mainly contributes to the piezoelectric property of the device which</p><p>becomes enhanced in the presence of external electrode polarization at high electric �ields du-</p><p>ring electrospinning. Here, the addition of GO improves the content of β phase of PVDF by in-</p><p>creasing nucleation sites. The device performance was further improved with the addition of</p><p>reduced graphene oxide (rGO) which enhanced β-phase content, resulting in a 700 nA short-</p><p>circuit current and 16 V open-circuit voltage. The higher conductivity of rGO facilitated impro-</p><p>ving the transfer of induced charge generated by PVDF, proving that rGO can enhance the pie-</p><p>zoelectric response of the �lexible �iber mat. Another recent work involved the use of</p><p>PVDF/nickel ferrite (NiFe O ) (400 nm diameter) nano�iber �ilms [191]. Electroactive proper-</p><p>ties of polymeric nanocomposites were signi�icantly in�luenced by the morphology of the na-</p><p>no�illers used. The larger aspect ratio formed a stronger interface with the matrix that impro-</p><p>ved the electroactive performance. Hence, the incorporation of NiFe O within PVDF �iber re-</p><p>sulted into transformation of microstructure from α-phase to β-phase by 68%. The fabricated</p><p>device exhibited ferroelectric properties with a highest polarization value of 1.46 μC/cm . In</p><p>vibrational testing mode, the sample showed a maximum saturation magnetization value of 4.2</p><p>emu/cm , open circuit voltage of 10 V, and 4.8 V output voltage under a weak AC magnetic �i-</p><p>eld of 10 Oe at 50 Hz.</p><p>2</p><p>2 4</p><p>2 4</p><p>2</p><p>3</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f009/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f009/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 33/50</p><p>Apart from nanogenerators, solar (photovoltaic) cells are also energy harvesting device that</p><p>converts light energy into electric energy. As the demand for cleaner energy is growing, solar</p><p>cells, capable of producing renewable energy have been widely explored for their portability,</p><p>ef�iciency, durability, and low maintenance. Nano�ibers have been extensively used for solar</p><p>cell research to achieve improved ef�iciency with other advantages like large scale production,</p><p>miniaturization, etc. There are mainly three types of photovoltaic devices: dye sensitized, pe-</p><p>rovskite, and organic cells which have been explored recently [192]. A few of the recent rese-</p><p>arch works are mentioned below.</p><p>Eco-friendly organic solar cells have several advantages, including biodegradability, safety, low-</p><p>cost, lightweight properties, large surface areas, and nontoxic characteristics. Lin et al.</p><p>successfully developed Ag NWs embedded TEMPO-oxidized eco-friendly cellulose nano�ibers</p><p>photovoltaic substrates using a facile, printable transfer method. In high-performance �lexible</p><p>OPVs, plastic �lexible substrates like polyethylene terephthalate (PET) and polyethylene</p><p>naphthalate (PEN) are mostly used, which have very high coef�icients of thermal expansion</p><p>that cause severe expansion or shrinkage, resulting in cracks. To avoid such damages, TEMPO-</p><p>oxidized Cellulose NFs were used here. It was observed that the TEMPO-mediated oxidation</p><p>largely improved mechanical strength of CNFs. Here, the nano�iber network enabled the for-</p><p>mation of a homogeneous hybrid with Ag NWs and concurrently allowed a higher percentage</p><p>of visible light. The device showed a low sheet resistance of 2.62 Ω sq with 78.5% optical</p><p>transparency of (at 550 nm), which was comparable to the commercial polyethylene</p><p>naphthalate/indium-tin-oxide substrate. The device was able to withstand 15 peeling cycles</p><p>and 500 bending cycles, displaying its high mechanical stability and very low thermal expan-</p><p>sion coef�icient (3.37 × 10 K ) that aided in obtaining a new perspective for the develop-</p><p>ment of sustainable organic photovoltaics [193].</p><p>In spite of many advantages, there are few drawbacks such as low ef�iciency, stability, and</p><p>strength, which triggered research interest in looking for other alternatives. A recent study on</p><p>iron platinum (FePt)/Titanium dioxide (TiO ) nano�ibers-based solar cell was conducted by</p><p>Nien et al. [194]. The device was fabricated onto the photoanode material for dye-sensitized</p><p>solar cell using sol-gel and electrospinning technique. Here, TiO nano�ibers acted as a barrier</p><p>layer which reduced the charge transfer resistance by preventing recombination of photogene-</p><p>rated electrons and holes. As FePt nanoparticles exhibit high chemical stability and coercivity</p><p>in addition to their excellent magnetic property, they can reduce the surface charge recombina-</p><p>tion rate of metal oxides. Hence, in this study, FePt nanoparticles were mixed with TiO nano�i-</p><p>bers to modify the photoanodes. The device showed an output intensity of 100 mW/cm and a</p><p>16% increase in photoelectric conversion ef�iciency when compared with the TiO photoa-</p><p>node, which was 3.79%, and FePt/TiO nano�iber photoanode, which was 4.41%. In general,</p><p>solar cell transparency is a crucial factor to capture and utilize the solar energy. In this direc-</p><p>tion, a study involving fabric-like transparent electrode for �lexible perovskite solar cell was</p><p>carried out by Zhai et al. [195]. In this work, a silver nanowire network-loaded PU/PAN nano�i-</p><p>bers �ilm was fabricated. Here, a nano�iber �ilm of approximate thickness of 10 µm provided</p><p>high transmittance and served as an excellent �lexible electrode. It was noticed that with incre-</p><p>asing PAN content, although the breaking strength enhanced, the light transmittance value de-</p><p>creased. The produced electrode possessed 80% light transmission in the visible range, and</p><p>70% break strain while retaining its original charge transport property during stretching and</p><p>bending operations. Hence, employing this electrode to assemble perovskite solar cells resul-</p><p>ted a 4.06% conversion ef�iciency while maintaining above 85% of its original ef�iciency.</p><p>−1</p><p>−6 −1</p><p>2</p><p>2</p><p>2</p><p>2</p><p>2</p><p>2</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 34/50</p><p>The roles of different nano�iber materials used in various nanogenerator applications are</p><p>summarized in Table 6.</p><p>Table 6</p><p>Roles of nano�iber materials in various nanogenerator applications.</p><p>Materials Property	and	Role Applications Ref.</p><p>Ethyl cellulose/polyamide 6 nano�iber</p><p>mats and MXene-based poly(vinylidene</p><p>�luoride) nano�iber mats</p><p>Ethyl cellulose/polyamide 6</p><p>nano�iber mats as triboelectric</p><p>cathode materials and MXene-</p><p>based PVDF nano�iber mats as</p><p>triboelectric anode materials.</p><p>Triboelectric</p><p>nanogenerator</p><p>[186]</p><p>Polyvinylidene �luoride (PVDF)/MXene</p><p>(Ti C T ) composite nano�ibers</p><p>The dielectric modulation of</p><p>PVDF nano�ibers by incorporating</p><p>conductive MXene nanosheets</p><p>signi�icantly enhanced the</p><p>dielectric constant and the surface</p><p>charge density of nano�iber by</p><p>270% and 80%, respectively.</p><p>Triboelectric</p><p>nanogenerator</p><p>[196]</p><p>Polyimide/poly(vinylidene �luoride-co-</p><p>tri�luoroethylene) membranes</p><p>Provided excellent triboelectric</p><p>negativity and high dielectric</p><p>constant</p><p>Triboelectric</p><p>nanogenerator</p><p>[187]</p><p>Polyamide 66 nano�iber and</p><p>poly(vinylidene�luorideco-</p><p>tri�luoroethylene) nano�iber</p><p>Nano�ibers were used as the shell</p><p>to wrap commercial stainless-</p><p>steel yarns providing high</p><p>�lexibility, desirable breathability,</p><p>washability, excellent durability,</p><p>demonstrating to be a reliable</p><p>power textile to light up 58 light-</p><p>emitting diodes</p><p>Triboelectric</p><p>nanogenerator</p><p>[197]</p><p>Graphene Oxide/PVDF Electrospun</p><p>Nano�iber</p><p>By adding GO and rGO to increase</p><p>the nucleation sites in PVDF, the</p><p>polar β piezoelectric phase could</p><p>be enhanced, resulting in greater</p><p>piezoelectric output</p><p>Piezoelectric</p><p>nanogenerator</p><p>[190]</p><p>PVDF-graphene nanosheet composite</p><p>nano�ibers</p><p>In comparison with the pristine</p><p>PVDF, the PVDF/G composite</p><p>�ilms-based TENGs demonstrated</p><p>superior triboelectric</p><p>performance.</p><p>Triboelectric</p><p>nanogenerator</p><p>[198]</p><p>Electrospraying pre-synthesized</p><p>ZnO nanorods on PVDF</p><p>nano�ibers resulted in the highest</p><p>3 2 x</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/table/polymers-13-03746-t006/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 35/50</p><p>4. Conclusions</p><p>This article was structured and presented in a format to provide an understanding of the state-</p><p>of-the-art properties, characteristics, and advanced applications of nano�iber technology. Na-</p><p>no�ibers with high surface area and tunable porosity, along with other novel properties like</p><p>high conductivity, superior electrochemical activity, improved mechanical strength, structural</p><p>integrity, etc., are being fabricated through the unique, simple, lucrative, and versatile techni-</p><p>que of electrospinning. The ability to affect nano�iber morphology with respect to the electros-</p><p>pinning setup modi�ications, along with environmental, solution, and process parameters, was</p><p>discussed in the review. Applications including biosensors, tissue engineering, wound healing,</p><p>and drug delivery in health care sector and batteries, supercapacitors, solar cells, and nanoge-</p><p>nerators in energy devices were elaborated in this article. Although electrospinning is the most</p><p>versatile among existing techniques, there are a few drawbacks such as: requirement of high</p><p>voltage and conducting targets; dif�iculty in achieving in situ deposition; scalability for mass</p><p>production; requirement of specialized equipment and reproducible systems for commerciali-</p><p>zation; dif�iculty in obtaining long, continuous, and oriented nano�iber; avoiding beads forma-</p><p>tion during electrospinning caused by solution viscosity or net charge density that reduces ef-</p><p>fective surface area of �ibers; becoming friable after calcination; and dif�iculty in fabricating na-</p><p>no�ibers with diameters less than 10 nm, etc. Along with these, there are also application-speci-</p><p>�ic shortcomings for each �ield. In health care applications, despite having unique properties,</p><p>electrospun nano�ibers show a low level of biodegradability, poor in�iltration of cells or drugs</p><p>into the scaffolds, and a consistency mismatch between the nano�ibers and bone extracellular</p><p>matrix, etc. Similarly, some challenges have also been faced in the applications of electrospun</p><p>nano�ibers-based energy devices. Some of these are inef�icient inhibition, unavailability of ef�i-</p><p>cient and durable redox activation and stability, limited theoretical speci�ic capacity, the need of</p><p>improved energy density, reproducibility, extended shelf life, and longer cycle life, etc.</p><p>The drawbacks and challenges that are being faced currently have become the problem state-</p><p>ment for future research works. Commercialization and meeting the demand of nano�iber</p><p>technology have become prime focuses for future research which aim towards large-scale pro-</p><p>duction for facilitating laboratory-to-market transition. The brittleness of electrospun nano�i-</p><p>bers is also a major setback for various applications, which has become another triggering fac-</p><p>tor for upcoming research, especially on developing highly �lexible continuous �ibers. To obtain</p><p>synergistic chemical as well as physical characteristics, the addition of nano�illers within the �i-</p><p>ber matrix has become another key researched area for both biomedical and energy related</p><p>applications. In the case of tissue engineering, wound dressing, and drug delivery, qualitative to</p><p>quantitative analysis for cytocompatibility of the �ibrous scaffolds for cell adhesion, prolifera-</p><p>tion, and differentiation is becoming an essential feature. Along with this, exploration through</p><p>in vivo animal/human study with clinical trials for evaluating real-life practical applicability of</p><p>the device or scaffold should also be emphasized. On the other hand, in energy devices,</p><p>synthesizing nano�iber-based electrodes with optimized porosity and pore distance for impro-</p><p>ving ion carrying and storing capacity is one of the upcoming major goals which will</p><p>subsequently enhance both voltammetric energy and power density. The aim of this review</p><p>was to provide an overall insight on electrospun nano�ibers and their advanced applications</p><p>through understanding the direction of research that has been conducted in the past 2 years</p><p>in the �ields of health care and energy devices.</p><p>Acknowledgments</p><p>02/02/2023 12:19</p><p>Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 36/50</p><p>V.S.R. would like to acknowledge the support given by the NUS Research Scholarship</p><p>(GRSUR5000003 RES SCH PhD SERIS IS) during the period of study.</p><p>Author Contributions</p><p>Conceptualization, writing—original draft preparation and editing, V.S.R.; writing and diagram</p><p>drawing Y.T., C.Z., Z.Y., K.R., A.C.; writing and editing, R.G.; supervision, R.G., S.R. and W.L.; project</p><p>administration, S.R.; funding acquisition, S.R. All authors have read and agreed to the published</p><p>version of the manuscript.</p><p>Funding</p><p>Sustainable Tropical Data Center (Grant No. R265000A50281), NUS COVID-19 Research Seed</p><p>Funding (Grant No. NUSCOVID19RG-11), Lloyd’s Register Foundation, UK (Grant No.</p><p>R265000553597), and the NUS Hybrid-Integrated Flexible (Stretchable) Electronic Systems</p><p>(HiFES) Program Seed Fund (Grant No. R265000628133).</p><p>Institutional Review Board Statement</p><p>Not applicable.</p><p>Informed Consent Statement</p><p>Not applicable.</p><p>Data Availability Statement</p><p>Not applicable.</p><p>Conflicts of Interest</p><p>The authors declare no con�lict of interest in�luencing the representation or interpretation of</p><p>re-ported research results.</p><p>Footnotes</p><p>Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional</p><p>affiliations.</p><p>References</p><p>1. What Is the Fourth Industrial Revolution? 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12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/</p><p>attention because of their ability to provide higher energy harvesting</p><p>ef�iciency, conversion ef�iciency, durability, and power density due to their high surface area</p><p>and controllable porosity [38]. Apart from energy devices and health care applications, there</p><p>are other miscellaneous applications of nano�ibers such as fabric technology [39], catalysis</p><p>[40], fuel cells [41], �iltration [42], and etc., which are also highly studied.</p><p>Over the past few decades, the global market value of the health care sector, energy devices,</p><p>and smart fabric technologies has been escalating while crossing the thousand-billion-dollar</p><p>mark. Along with that, in the near future, market value with innovation is predicted to go far</p><p>beyond. This review article provided a broad survey on the contribution of electrospun</p><p>technology over the past 2–3 years in these application �ields through discussing the most re-</p><p>cent developments accompanied with current and future research trends. The role of nano�i-</p><p>bers and associated device performance as well as advantages and disadvantages of each ap-</p><p>https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=8587893_polymers-13-03746-g002.jpg</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f002/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 4/50</p><p>plication were emphasized in detail. Here, we anticipated the future scope and direction th-</p><p>rough summarizing the drawbacks faced in the current research scenario. This article is orga-</p><p>nized as follows: in the �irst section, we discuss various aspects of the electrospinning process,</p><p>including setup, spinning, solution, and environmental parameters. The following section of</p><p>this article focuses on the most recent research, including the past 2 years of work while</p><p>emphasizing the role of nano�ibers, their structure, and device performance. Finally, we con-</p><p>clude by addressing existing challenges which should be addressed for future perspectives.</p><p>2. Morfologia de nanofibras e técnicas de eletrofiação</p><p>2.1. Propriedades</p><p>Os materiais de nano�ibras, devido à sua morfologia nanoestruturada unidimensional, são per-</p><p>cebidos como tendo propriedades superiores quando comparados aos materiais a granel. Vá-</p><p>rias propriedades únicas, como seu pequeno tamanho, maior mobilidade do transportador,</p><p>maior área de superfıćie especı�́ica e alta relação superfıćie-volume, ajudaram no surgimento</p><p>da tecnologia de nano�ibras, introduzindo nano�ibras como um material ativo apropriado para</p><p>várias aplicações nos campos da eletrônica. , biomedicina, armazenamento de energia, saúde,</p><p>tecnologia de tecidos, etc. [ 43]. Essas nano�ibras podem fornecer mobilidade efetiva como</p><p>transportadoras de caminho 1D, diminuindo os limites com grãos de cristalitos adjacentes em</p><p>eletrônicos �lexıv́eis. Seu tamanho e área de superfıćie especı�́ica maior ajudam a responder</p><p>mais rapidamente a estıḿulos externos, enquanto sua alta proporção facilita propriedades me-</p><p>cânicas e fıśicas ajustáveis. Essas propriedades notáveis envolvem tolerância para �lexão ou</p><p>alongamento mecânico [ 44 , 45 ], condutividade elétrica aprimorada [ 46 ], baixa densidade,</p><p>maior área de superfıćie especı�́ica [ 47 ], boa óptica [ 48 ], térmica [ 49 ], optoeletrônica [ 50</p><p>], e propriedades elétricas [ 51 ], alta relação de aspecto [ 52], boa transparência [ 53 ] e geo-</p><p>metria conveniente com volume e tamanho de poros ajustáveis [ 54 ]. Nos últimos 100 anos,</p><p>os pesquisadores sintetizaram nano�ibras esticando eletrostaticamente a solução de polıḿero</p><p>viscoso em forma �ibrosa através da técnica de eletro�iação [ 55 ]. Normalmente, este método</p><p>é aplicável a polıḿeros sintéticos e naturais, juntamente com ligas poliméricas e polıḿeros car-</p><p>regados com nanopartıćulas, metais, cerâmicas ou quaisquer outros agentes ativos [ 56 ]. Os</p><p>polıḿeros possuem propriedades quıḿicas inertes e, portanto, a produção de nano�ibras poli-</p><p>méricas fornece um benefıćio estrutural em modi�icações de superfıćie ajustáveis para propri-</p><p>edades desejadas em aplicações especı�́icas [ 57 ].</p><p>2.2. Parâmetros de eletrofiação e seu significado</p><p>Vários fatores afetam a morfologia da nano�ibra e a uniformidade no processo de eletro�iação.</p><p>Esses fatores envolvem parâmetros da solução precursora, parâmetros de con�iguração do</p><p>processo e condições ambientais.</p><p>Concentração, peso molecular, tensão super�icial, constante dielétrica, viscosidade e condutivi-</p><p>dade da solução são os parâmetros que afetam a solução precursora para a formação de na-</p><p>no�ibras [ 58 ]. Estudos comprovam que a forma da gota de polıḿero ejetada pela seringa se</p><p>transforma de esférica para fusiforme, eventualmente formando �ibras com diâmetro uni-</p><p>forme, semelhante e aumentado com o aumento da concentração da solução [ 59 ]. Peso mole-</p><p>cular, concentração de polıḿero e viscosidade estão correlacionados e têm um impacto geral</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 5/50</p><p>na formação de nano�ibras [ 60 , 61]. Em geral, o peso molecular polimérico está correlacio-</p><p>nado com o grau de emaranhamento da cadeia polimérica que permite determinar a formação</p><p>de �ibras com grânulos ou �ibras limpas [ 62 , 63 ]. No processo de eletro�iação, a maior tensão</p><p>super�icial causa instabilidade na formação do jato no bico, o que resulta na formação de go-</p><p>tas por pulverização em vez da formação de �ibras e, portanto, uma solução com menor tensão</p><p>super�icial é preferida [ 64 ]. A viscosidade da solução precisa ser ideal para a geração de �i-</p><p>bras, pois a viscosidade extrema da solução resulta em uma liberação de jato instável [ 65]. A</p><p>viscosidade é variada pela proporção de soluto (polıḿero ou composto de polıḿero) e sol-</p><p>vente. O teor de polıḿero deve ser ideal para a formação de nano�ibras perfeitas [ 66]. A con-</p><p>dutividade da solução é amplamente in�luenciada por alguns parâmetros-chave: tipo de polı-́</p><p>mero, solvente e teor de sal (grau de ionização). O diâmetro da nano�ibra diminui com o au-</p><p>mento da condutividade da solução, enquanto uma redução na condutividade da solução leva</p><p>à formação de jato alongado, causando não uniformidade e formação de grânulos ou mesmo</p><p>obstrução no �luxo da solução. Por outro lado, soluções com condutividade excessiva resultam</p><p>em extrema instabilidade de �lexão e ampla variação do diâmetro da �ibra na presença de altas</p><p>tensões. Por essas razões, uma condutividade de solução ideal é necessária para otimizar a</p><p>morfologia da �ibra, bem como o diâmetro da �ibra [ 67 , 68]. Além disso, a natureza do sol-</p><p>vente é outro fator decisivo para a �iação e porosidade da nano�ibra. Durante a eletro�iação,</p><p>antes que o jato atinja a plataforma coletora, ocorre uma separação de fases para formar na-</p><p>no�ibras sólidas. A volatilidade do solvente pode in�luenciar fortemente este processo modu-</p><p>lando a taxa de evaporação efetiva. 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Flow rate con-</p><p>trols the amount of polymer being released for �iber formation, which requires adjusting and</p><p>deciding based on the solution viscosity. Generally, lower �low rate is advised as it provides a</p><p>longer time for solvent evaporation [72]. Nozzle-to-collector distance provides time for the</p><p>polymer solution to convert into a �iber while facilitating solvent evaporation [69].</p><p>Apart from solution and process conditions, environmental parameters such as humidity and</p><p>temperature also in�luence the nano�iber morphology. Temperature changes the solution</p><p>viscosity, which in turn affects the spinning process [63]. Whereas, humidity effects the rate at</p><p>which solution evaporation occurs [73]. For obtaining nano�ibers with different morphologies,</p><p>optimized parameters along with modi�ied electrospinning setup are utilized.</p><p>2.3. Electrospinning Setup Modifications</p><p>A conventional electrospinning setup consists of a spinning electrode, solution holder, pushing</p><p>pump, spinneret, high-voltage power supply, and a grounded collector. Since the development</p><p>of the electrospinning process, several modi�ication techniques have emerged in order to pro-</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 6/50</p><p>vide tailored morphology to the nano�ibers. Some of these techniques involve coaxial, gas-as-</p><p>sisted, porous hollow tube, multi-jet, self-bundling, and roller electrospinning [58,74].</p><p>Coaxial electrospinning is generally employed to fabricate core-shelled structured nano�ibers.</p><p>Here, two solutions are used, in which one acts as a sheath (shell) and the other acts as a core.</p><p>Two syringes are used in the working with different solutions which are pushed</p><p>simultaneously to release the material through their respective capillaries and facilitate forma-</p><p>tion of composite nano�ibers, illustrated in Figure 3a [75]. Solution compatibility (either immis-</p><p>cible or semi-miscible), viscosity ratio of core-to-shell solution, and concentration are the key</p><p>controlling factors for coaxial electrospinning [7]. Gas-assisted spinning is another technique</p><p>that especially aids in the spinning of polymer solution with lower conductivity, which is dif�i-</p><p>cult to spin in the normal setup. Figure 3b exhibits the electrospinning setup. In this technique,</p><p>either high-velocity hot air or compressed air is used to make the �ibers �iner [76], with high</p><p>surface area, barrier properties, and insulation value [77]. In multi-jet electrospinning shown</p><p>in Figure 3c, the basic notion involves obtaining higher productivity by increasing the number</p><p>of solution jets by implementing different methods [78]. Some of these methods involve the</p><p>application of an external electric �ield [79], using a curved collector [80], splitting the jets to</p><p>form separate sub-jets [81], and using multiple needles and needleless systems [82]. This tech-</p><p>nique enables improved production ef�iciency along with cost-effectiveness as a result of elec-</p><p>trospinning through multiple nozzles [69]. Bubble electrospinning is performed by a porous</p><p>hollow tube, which is a needleless process, and the polymer solution is pushed through the po-</p><p>res of a walled cylindrical tube that facilitates the formation of hollow nano�ibers [83]. There</p><p>are various ways of forming hollow nano�ibers by bubble electrospinning or blown bubble</p><p>spinning, in which several bubbles are generated on the solution surface using a gas pump</p><p>Figure 3d [84,85]. This is one of the most promising needleless electrospinning with advanta-</p><p>ges like high productivity and lower energy consumption due to the utilization of a third force</p><p>that helps in overcoming the surface tension [86].</p><p>Figure 3</p><p>(a) Schematic of the coaxial electrospinning system [87]. (b) Illustrative set-up used in the gas-assisted elec-</p><p>trospinning process [88]. (c) Experimental setup of the multi-jet electrospinning [89]. (d) Graphic represen-</p><p>tation of the bubble electrospinning technique [90].</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f003/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f003/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f003/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f003/</p><p>https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=8587893_polymers-13-03746-g003.jpg</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f003/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 7/50</p><p>Besides these, a few other application-speci�ic electrospinning setups include the charge-injec-</p><p>tion method [91], near-�ield electrospinning [92], solvent-free electrospinning including super-</p><p>critical CO2-assisted electrospinning [93], magnetic �ield-assisted [94], anion-curing electros-</p><p>pinning, and UV-curing electrospinning [95], etc.</p><p>3. Applications of Nanofibers</p><p>The evolution of electrospinning technology and the ability to fabricate tunable nano�ibers</p><p>have facilitated the development of advanced applications in the �ields of health care, energy</p><p>devices, the textile industry, environmental appliances, etc.</p><p>3.1. Health Care</p><p>Being a dominant and necessary sector, health care, or biomedical applications, is of the ut-</p><p>most importance and has become a highly explored area by researchers. As a potential solu-</p><p>tion to various challenges faced in the �ield of biomedicine, nano�iber technology is bene�icial</p><p>and has attractive properties. Resolutions such as organ repair, crucial vital monitoring, burns</p><p>and wound dressing, blood puri�ication, treatment for various diseases, and etc. have been of-</p><p>fered by nano�iber technology [96].</p><p>3.1.1. Biosensors Biosensors are analytical tools that assist in the detection, quanti�ication, and</p><p>monitoring of various analytes such as enzymes, bacteria, cells, nucleic acids, antibodies, etc.</p><p>present in human body [97]. Such devices require high selectivity along with sensitivity</p><p>towards analytes where incorporation of nano�iber technology has demonstrated tremendous</p><p>potential [98]. Using nano�ibers, miniaturization of the sensing platform was made possible,</p><p>which can act in both micro/nano as well as the macro-scale while providing accurate results</p><p>[99]. Sensing platforms are classi�ied based on different types of transducers such as electro-</p><p>chemical, magnetic, thermometric, those involving optical �luorescence, luminescence, and ab-</p><p>sorbance, electromechanical, amperometric, potentiometric, etc. [96]. In general, these devices’</p><p>performances are quanti�ied in terms of selectivity, linearity, sensitivity, response time,</p><p>reproducibility, linear range, and limit of detection [100].</p><p>In this �ield, researchers have utilized dimension, porosity, and the surface-to-volume ratio of</p><p>nano�ibers to develop highly ef�icient antibody detectors [101].</p><p>Nefastin	Antibody	Detection	 For example, in their recent work, Kim et al. [102] developed FET</p><p>(�ield-effect transistor) biosensors for nesfatin-1 antibody detection using multiscale pore-con-</p><p>tained carbon nano�ibers. 1D carbon nanomaterials are preferred as channel materials in FET</p><p>biosensors as they can be easily tuned to immobilize the bioreceptors through π-stacking or</p><p>covalent bonds. In this work, carbon nano�ibers acted as signal transducers and templates for</p><p>the immobilization of the nesfatin-1 antibody, achieving a low limit of detection (LOD) of 0.1 fM</p><p>and a fast detection time of less than a second due to their multiscale porous structure. Elec-</p><p>trospun �ibers have also been explored for DNA detection.</p><p>transparent electrodefor �lexible</p><p>perovskite solar cell. Thin	Solid	Film.	2021;729:138698. doi: 10.1016/j.tsf.2021.138698. [CrossRef] [Google Scholar]</p><p>196. Bhatta T., Maharjan P., Cho H.O., Park C., Yoon S.H., Sharma S., Salauddin M., Rahman M.T., Rana S.M.S., Park J.Y.</p><p>High-performance triboelectric nanogenerator based on MXene functionalized polyvinylidene �luoride composite</p><p>nano�ibers. Nano	Energy.	2020;81:105670. doi: 10.1016/j.nanoen.2020.105670. [CrossRef] [Google Scholar]</p><p>197. Guan X., Xu B., Wu M., Jing T., Yang Y., Gao Y. 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Recently, Civan et al.</p><p>[103] synthesized a hybrid cellulose nano�iber to monitor guanine-base oxidation in single-</p><p>strand DNA by electrochemical methods. Because of its biocompatibility as well as its mechani-</p><p>cal, physical, and chemical properties, cellulose is used for a variety of applications. When con-</p><p>verted into �ibrous form high surface-to-volume ratio, it provides a larger number of DNA mo-</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 8/50</p><p>lecules to be absorbed on the surface, supporting higher sensitivity. Here, hybrid nano�ibers</p><p>were synthesized by the electrospinning of cellulose monoacetate and tetraethyl orthosilicate.</p><p>The �iber diameter, here, was controlled by the catalyzer and hydrochloric acid and attained</p><p>between 42–958 nm. Here, the nano�iber played a role in monitoring guanine-base oxidation</p><p>in single-strand DNA by electrochemical methods.</p><p>Glucose	Sensing	 In the �ield of glucose sensing, electrospun nano�iber-based biosensors are</p><p>highly explored because of their high surface area, which provides a large immobilization site</p><p>resulting in increased interaction with analytes, shorter detection time, and increased lifetime</p><p>[104]. A novel self-powered glucose biosensor was developed by Li et al. [105], as depicted in</p><p>Figure 4a. The synthesis process involves encapsulation of the enzyme into a zeolitic imidazo-</p><p>late metal organic framework (ZIF-8) during in-situ growth on cellulose acetate (CA) nano�i-</p><p>bers. In �inal device, highly �lexible electrodes were prepared by step-by-step adsorption of</p><p>MWCNTs and AuNPs on CA/ZIF-8@enzyme membranes. Here, due to its hydrophilic nature,</p><p>cellulose can act as an inherent electrolyte reservoir where porous �ibrous structure helps in</p><p>transferring the diffused ions within electrolytes and electrochemically active materials. On the</p><p>other hand, in-situ growth of ZIF-8 not only provides a successful enzyme encapsulation</p><p>strategy, but also improves the enzyme stability aided by structural constraints. The addition of</p><p>CNTs promotes direct electron transfer within the device. BET surface area values for CA nano-</p><p>�ibers and CA/ZIF-8@enzyme/MWCNTs/Au were 9.879 m g and 99.356 m g ,</p><p>respectively. Here, inclusion of ZIF-8 crystal within CA �iber network contributed in achieving</p><p>higher porous structure and high absorption capacity. During cyclic voltammetry measure-</p><p>ments, signi�icant redox peaks were observed at ~0.39 V and ~0.51 V. These nano�iber mem-</p><p>branes showed long-term stability up to 15 h. Recently, another glucose sensor was reported</p><p>by Sapountzi et al. [106]. Here, polyacrylonitrile (PAN) nano�iber mats of 650 ± 10 nm diame-</p><p>ter coated with conductive polypyrrole (PPy) layers were produced by a two-step process in-</p><p>volving electrospinning and vapor-phase polymerization. The electrospun PAN NFs acted as a</p><p>backbone with a non-conductive structure (core �ibers) whilst facilitating the growth of PPy-</p><p>based coatings onto their surfaces. Here, the carboxyl group nano�ibers introduced into the</p><p>PPy coatings enabled covalent binding of a model enzyme, glucose oxidase, which was utilized</p><p>for the detection of glucose content. The device could act within a broad detection range of 20</p><p>nM–2 μM glucose concentration with a very low detection limit of 2 nM. Another electrochemi-</p><p>cal biosensor for glucose detection was synthesized by decorating Cu-nano�lower onto the</p><p>gold nanoparticles (AuNPs)/graphene oxide (GO) PVA nano�iber (Figure 4b). GO acted as a �i-</p><p>ber precursor, improving electrochemical properties of the �iber matrix. It was further decora-</p><p>ted with AuNPs via electrostatic interaction to increase electrical conductivity and detection</p><p>sensitivity. Finally, the surface coating of unique organic-inorganic nanostructured materials</p><p>(Cu-nano�lower) enhanced catalytic properties. These composite nano�ibers facilitated in</p><p>yielding an ef�icient electro-catalyzed reaction that converted glucose to gluconic acid. The �inal</p><p>device, Cu-nano�lower@AuNPs-GO NFs-coated Au chip, exhibited a wider linear range (0.001–</p><p>0.1 mM) with LOD of 0.018 μM [107].</p><p>2 −1 2 −1</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f004/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f004/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 9/50</p><p>Figure 4</p><p>(a) Schematic of the self-powered glucose biosensor; SEM-EDS elemental mapping images of CA/ZIF-</p><p>8@enzyme/MWCNTs/Au electrode; BET analysis of as-prepared samples [105]. (b) Schematic illustration</p><p>for the fabrication of Cu-nano�lower/AuNPs-GO NFs-based electrochemical glucose biosensor and FE-SEM</p><p>image formation of Cu-nano�lowers [107].</p><p>β-Amyloid	Detection	 Another type of electrochemical sensor has been recently developed by</p><p>Supraja et al. [108] using electrospun Tin oxide (SnO ) nano�iber. These were used for label-</p><p>free detection of β-Amyloid (1–42) in early-stage diagnosis of Alzheimer’s Disease. This hor-</p><p>mone-speci�ic capture antibody was covalently immobilized on the carbon electrode modi�ied</p><p>by SnO nano�ibers. SnO is an intrinsic n-type semiconductor containing a number of oxygen</p><p>vacancies present at the grain boundaries. These vacancies enable absorption of external mo-</p><p>lecules which increases Schottky barrier height, resulting in a reduction of conductivity which</p><p>in turn controls the electrical behavior of the sensor. This inherent heterogeneity of SnO can</p><p>facilitate target analyte detection in fairly low concentrations of analyte. It has been noted that</p><p>within the concentration range of 1 fg/mL μg/mL, the sensing platform shows a sensitivity of</p><p>274.96 (kΩ/ng.mL )/cm and 0.146 fg/mL LOD.</p><p>Levodopa	Detection	 In another study Wang et al. [109] used Molybdenum disul�ide (MoS ) na-</p><p>nosheet arrays/carbon nano�ibers. These nano�ibers were used as an electrode in a biosensor</p><p>for detection of levodopa and uric acid. MoS nanosheet arrays are promising materials for</p><p>sensing applications due to their large surface area, excellent conductivity, high catalytic</p><p>ef�iciency, and biocompatibility. When combined with nano�ibers, the composite material pos-</p><p>sessed high electronic conductivity with improved electrochemical active sites by increasing</p><p>the speci�ic surface area of CNFs network. These composite nano�ibers facilitated in achieving</p><p>stability, good repeatability, and higher sensitivity (0.91 μA μM for levodopa and 0.73 μA</p><p>μM for uric acid) within the range of 1–60 μM.</p><p>2</p><p>2 2</p><p>2</p><p>−1</p><p>−1 2</p><p>2</p><p>2</p><p>−1</p><p>−1</p><p>https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=8587893_polymers-13-03746-g004.jpg</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f004/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 10/50</p><p>H O 	Detection	 In the �ield of biosensing, hydrogen peroxide (H O ) detection plays an impor-</p><p>tant role for disease determination, as it is a common by-product of some biochemical proces-</p><p>ses, catalyzed by enzymes (such as glucose oxidase, cholesterol oxidase etc.) and triggering</p><p>cancer growth. Daemi et al. [110] worked in a non-enzymatic biosensor for H O detection</p><p>with ZnO-CuO hybrid nano�iber that has a sensitive amperometric response and LOD of 2.4</p><p>µM. Though ZnO is a low-cost inorganic n-type semiconductor with a wide band gap of 3.37 eV,</p><p>high mobility, and non-toxicity, it suffers from weak cycling performance when used as an elec-</p><p>trode material. To address this issue, CuO (a p-type stable semiconductor with narrow band</p><p>gap 1.2–1.9 eV) was incorporated to synthesize a hybrid nanostructure which provided</p><p>synergetic electrochemical sensing properties due to the presence of binary metal oxides. This</p><p>hybrid nano�iber exhibited the lowest charge transfer resistance and the highest</p><p>electrocatalytic performance among other modi�ied electrodes used for the detection of H O .</p><p>Among various biosensing platforms, FETs have diverse applications in the detection of</p><p>enzyme, immune, DNA, cell-based materials with advantages like fast response speed, accurate</p><p>detection, low cost, and low power consumption. Recently, Hong et al. [111] fabricated In-Ga-</p><p>Zn-O nano�iber-based double-gate FETs biosensors for chemical sensing with high sensitivity</p><p>(998 and 383 mV/pH, pH sensitivities for In-Ga-Zn-O nano�iber and In-Ga-Zn-O �ilm-based sen-</p><p>sors respectively). Here, In-Ga-Zn-O nano�iber was synthesized by electrospinning of In-Ga-Zn-</p><p>O precursor along with polyvinylpyrrolidone (PVP) polymer. Unlike the conventional chemical</p><p>vapor deposition or solution-processing methods, here, electrospinning was employed to</p><p>synthesize In-Ga-Zn-O nano�ibers that improved a capacitive coupling effect. These �ibers were</p><p>applied to the channel layers to increase the sensitivity without adjusting the gate-oxide mate-</p><p>rials or thickness.</p><p>Depending on the origin of the polymers, these biosensors can also be classi�ied into two ma-</p><p>jor categories: natural and synthetic polymer-based biosensors, as shown in Table 1. These</p><p>studies include natural polymers like cellulose, CA, etc., and synthetic polymers like PVA, PAN,</p><p>PPY, PVP, etc. for developing biosensors for their biocompatibility, biodegradability, and non-to-</p><p>xic nature.</p><p>2 2 2 2</p><p>2 2</p><p>2 2</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/table/polymers-13-03746-t001/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 11/50</p><p>Table 1</p><p>Role of nano�iber materials in various biosensing applications.</p><p>Polymer</p><p>Type</p><p>Materials Property	and	Role Applications Ref.</p><p>Natural</p><p>polymer</p><p>Cellulose</p><p>Monoacetate/Tetraethyl</p><p>Orthosilicate Hybrid</p><p>Nano�ibers</p><p>Monitored guanine base</p><p>oxidation in single-strand DNA</p><p>by electrochemical methods</p><p>Electrochemical</p><p>DNA biosensor</p><p>[103]</p><p>Natural</p><p>polymer</p><p>Cellulose acetate nano�iber</p><p>CA/ZIF-</p><p>8@enzyme/MWCNTs/Au</p><p>membranes were utilized as</p><p>highly �lexible electrodes</p><p>Glucose biosensor [105]</p><p>Synthetic</p><p>polymer</p><p>Activated multiscale pore</p><p>contained carbon nano�iber</p><p>(a-MPCNF)</p><p>Signal transducer and template</p><p>for immobilization of nesfatin-1</p><p>antibody</p><p>FET (�ield-effect</p><p>transistor)-based</p><p>biosensor</p><p>[102]</p><p>Synthetic</p><p>polymer</p><p>In-Ga-Zn-O (IGZO)</p><p>nano�iber</p><p>Facilitated increase in the</p><p>sensitivity without adjusting</p><p>the gate-oxide materials or</p><p>thickness</p><p>FET-based</p><p>chemical and</p><p>biosensor</p><p>[111]</p><p>Synthetic</p><p>polymer</p><p>Polyacrylonitrile/</p><p>Polypyrrole Core-Shell</p><p>Nano�ibers</p><p>Facilitated covalent binding of</p><p>the enzyme, glucose oxidase</p><p>Glucose biosensor [106]</p><p>Synthetic</p><p>polymer</p><p>Copper nano�lower</p><p>decorated Au NPs graphene</p><p>oxide nano�iber</p><p>Enabled conversion from</p><p>glucose to gluconic acid</p><p>through electro-catalyzed</p><p>reaction while improving the</p><p>electrochemical properties</p><p>Glucose biosensor [107]</p><p>Synthetic</p><p>polymer</p><p>ZnO-CuO nano�ibers</p><p>Tuned nanostructure for</p><p>improved amperometric</p><p>detection of H O .</p><p>Non-enzymatic</p><p>biosensor</p><p>[110]</p><p>Synthetic</p><p>polymer</p><p>SnO nano�iber</p><p>β-Amyloid (1–42) is a viable</p><p>biomarker for early diagnosis of</p><p>Alzheimer’s Disease. Speci�ic</p><p>capture antibody was</p><p>covalently immobilized on the</p><p>SNF nano�iber-modi�ied carbon</p><p>working electrode for</p><p>immunoassay</p><p>Immunosensor [108]</p><p>Combined the high</p><p>2 2</p><p>2</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 12/50</p><p>3.1.2. Tissue Regeneration Regenerating the growth of cells and tissues is a part of tissue engi-</p><p>neering that aims to repair or replace function to the damaged tissues through biological prin-</p><p>ciples [69]. The major challenge in tissue engineering is the development of scaffolds that can</p><p>replicate tissue architecture at the nanoscale level. Nano�ibers have been used as basic buil-</p><p>ding blocks for tissue-regenerating scaffolds for the past few decades. They serve as an excel-</p><p>lent framework for cell adhesion, proliferation, and differentiation by meeting existing challen-</p><p>ges [114,115].</p><p>Among various existing techniques, electrospun nano�ibers are most widely used for tissue en-</p><p>gineering applications due to their higher surface area and porosity, which aid as favorable</p><p>factors for cell interactions [116,117]. Both natural and synthetic materials possessing</p><p>biocompatibility, biomimicking, hydrophilicity or hydrophobicity, polymer-drug adhesion, and</p><p>control over drug release have been extensively explored for these applications [114,118]. The</p><p>nano�ibers possessing these qualities are utilized in various types of tissue regeneration appli-</p><p>cations such as musculoskeletal (involving bone, ligament, cartilage, and skeletal muscle), vas-</p><p>cular, skin, neural, as carriers for the controlled delivery of drugs proteins, and DNA [119].</p><p>Few contemporary studies in the �ield of tissue regeneration through integration of nano�iber</p><p>technology were discussed here.</p><p>Bone	Tissue	Regeneration	 Bone tissue regeneration is a complicated procedure which depends</p><p>on several factors that involve maintaining the defect shape while preventing any further com-</p><p>pression to the initial blood clot, along with the capability to shield soft tissues cells in�iltration</p><p>during maturation of the bone matrix. At the same time, maintaining suitable mechanical pro-</p><p>perties for required regeneration timeline withholding appropriate biodegradability is also ne-</p><p>eded to avoid post-surgical complications [120]. Recently, Zhang and team [121] produced a</p><p>biodegradable synthetic scaffold for stimulating bone tissue repair. In this study, a mineralized</p><p>collagen and chitosan cast �ilm was coated with polycaprolactone (PCL)/polyvinylpyrrolidone</p><p>(PVP) electrospun nano�ibers and loaded with berberine (drug), which yielded a bilayer mem-</p><p>brane (Figure 5a). PCL, being a synthetic polymer, has good elasticity as well as</p><p>biodegradability and biocompatibility, which make it suitable for tissue engineering applicati-</p><p>ons. However, it suffers from low water absorption capacity and hydrophobicity. Hence, by</p><p>combining it with PVP, which is a water-soluble polymer, the biodegradation and hydrophilicity</p><p>of PCL can be improved. The bilayer membrane of uniform diameter (548 ± 150 nm) compo-</p><p>site nano�ibers showed favorable mechanical properties (Young’s modulus 120 MPa) while</p><p>enhancing the attachment and proliferation. For testing the practical applicability, this scaffold</p><p>was implanted within a rat femoral bone defect for in vitro attachment, proliferation, and rege-</p><p>neration of MC3T3-E1 (osteoblast precursor cell line) cells.</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f005/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 13/50</p><p>Figure 5</p><p>(a) Representation of the method of preparation and implantation of the bilayer membrane [121]. (b) Illustra-</p><p>tion of scaffolds synthesis their application for cartilage tissue engineering [123]. (c) Schematic of preparing</p><p>core-shell nano�ibrous scaffold and osteogenic differentiation of human mesenchymal stem cells into osteo-</p><p>blasts on the scaffolds [122].</p><p>Among various types of scaffolds, coaxial structures provide an environment conducive to</p><p>bone tissue regeneration, as they can encapsulate proteins, growth factors, drugs, and other</p><p>bioactive substances. As in these structures core solution does not need spinnability, these</p><p>substances are incorporated within the core structure which</p><p>is released in a sustained manner</p><p>for controlled therapy [14]. With the help of the coaxial electrospinning method, Rastegar et al.</p><p>[122] fabricated a platelet-rich �ibrin loaded/chitosan (CS) core-shell nano�ibrous scaffold. CS</p><p>holds various outstanding properties including biocompatibility, biodegradability, and antibac-</p><p>terial, which are required for biomedical applications. However, it cannot be electrospun alone</p><p>and thus should be blended with some polymers like PCL which has high solubility in organic</p><p>solvents and slow biodegradation. The core-shell nano�ibrous structure enhanced osteogenic</p><p>differentiation of mesenchymal stem cells (ability to self-renew and differentiate into multiple</p><p>cell) (Figure 5c) in this study. By loading �ibrin to the nano�iber structure, elastic modulus and</p><p>speci�ic surface area of the scaffold were observed to increase from 25 to 44 MPa and 9.98 to</p><p>16.66 m /g respectively.</p><p>Articular	Cartilage	Regeneration	 Cartilage degeneration is one of the most common joint disea-</p><p>ses. Due to the absence of blood vessels and the innervation network, the mature articular car-</p><p>tilage regeneration rate is poor, which may lead to various disabilities, affecting quality of life.</p><p>Recently, Chen et al. [123] engineered a gas-foamed extracellular matrix mimicking a 3D po-</p><p>rous electrospun nano�iber scaffold for articular cartilage regeneration. In this study, 2D elec-</p><p>trospun poly(L-lactide-co-e-caprolactone) (PLCL)/silk �ibroin (SF) scaffolds were fabricated by</p><p>a dynamic liquid support electrospinning system which was then cross-linked with hyaluronic</p><p>acid to mimic the microarchitecture of native cartilage (Figure 5b). PLCL-based scaffolds are</p><p>2</p><p>https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=8587893_polymers-13-03746-g005.jpg</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f005/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f005/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f005/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 14/50</p><p>extensively researched for tissue engineering applications due to their mechano-elastic and bi-</p><p>odegradable properties which impart mechanical stability in the scaffolds. Further addition of</p><p>SF improves the hydrophilicity and cytocompatibility of the hybrid nanostructures, meeting re-</p><p>quirements for the optimal cartilage regeneration. For the real-time application, the scaffold</p><p>was implanted within a rabbit model. It was observed that these fabricated 3D scaffolds</p><p>showed satisfactory proliferation and phenotypic maintenance of chondrocytes while exhibi-</p><p>ting good hemocompatibility, cytocompatibility, biocompatibility, and low density, high porosity</p><p>with a large pore area, good water absorption capacity, and mechanical stability.</p><p>Periosteal	Regeneration	 Found around the cortical bone, periosteum is a dense layer of vascu-</p><p>lar connective tissues, osteoprogenitor cells, and stem cells. It plays an important role in repai-</p><p>ring bone defects. However, existing arti�icial periosteum materials suffer with poor mechani-</p><p>cal properties and bionic structure construction, osteogenic differentiation, and vascularization</p><p>capabilities. In order to address this issue, Zhang and group [124] prepared poly-ε-caprolac-</p><p>tone (PCL)/whitlockite through electrospinning technology. PCL is an FDA-approved synthetic</p><p>polyester material with good processability and biocompatibility and moderate degradation</p><p>velocity which, is highly suitable for long-term in vivo usage. However, it lacks inherent osteoin-</p><p>ductive abilities, which limits its application. This can be improved by introducing calcium</p><p>phosphate (CaPs) like whitlockite. Whitlockite is the second-most-present CaP in natural bone</p><p>tissues which inhibits osteoclast activity, promoting angiogenesis. By testing this material in vi-</p><p>tro mineralization experiments, the rapid ion release from whitlockite was observed to pro-</p><p>mote the deposition of mineralized hydroxyapatite for human umbilical vein endothelial cell</p><p>angiogenesis and migration along with collagen formation and calcium deposition.</p><p>Dural	Regeneration	 Dura mater is the outermost layer of meninges that surrounds brain and</p><p>spinal cord. It provides cover and support to the dural sinuses and carries blood from the</p><p>brain to the heart. For healing and regeneration of this layer, a radially aligned nanoscale sur-</p><p>face is desirable as an arti�icial dural substitute. Hence scaffolds constructed with electrospun</p><p>nano�ibers could meet such a demand by guiding and enhancing cell migration from the edge</p><p>of a dural defect to the center [125]. The most commonly used synthetic dural substitutes ex-</p><p>perience local tissue rejection or in�lammation reactions induced by their acidic products,</p><p>which causes degradation by forming foreign-body giant cells through monocyte/macrophage</p><p>fusion. Hence, to achieve ef�icient dural healing, high molecular weight poly(4-</p><p>hydroxybutyrate) (P4HB) polymer-based nano�iber membranes were synthesized via electros-</p><p>pinning, which exhibited high elasticity, biocompatibility, and long-term strength retention pro-</p><p>perties. A cyto-compatible platform in which �ibroblasts can migrate, adhere, and proliferate</p><p>with the lower limit of 2.15 EU (endotoxin)/devices contacting cerebrospinal �luid was</p><p>successfully achieved with other characteristics such as conformability, wettability, and</p><p>strength to an underlying tissue surface, for dural tissue repair. In a rabbit duraplasty model in</p><p>vivo, the membrane could form a continuous neodural tissue mimicking native dura mater,</p><p>which produced a watertight closure to prevent cerebrospinal �luid leakage without systematic</p><p>or local infection [126].</p><p>Olfactory ensheathing cells comprise a type of glial cell which can penetrate the transition zone</p><p>between the peripheral and central nervous systems. They play a key role in central nervous</p><p>system repair as seed cells. Many studies have reported that the diameter of electrospun nano-</p><p>�ibers has a signi�icant effect on cell behavior along with cell adhesion, viability, morphology,</p><p>differentiated functions, and proliferation [127,128]. Castano and group [129] produced func-</p><p>tionalized nanoscale meshes of PLA nano�ibers, seeded with chemotactic TEG3 cells, an</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 15/50</p><p>olfactory ensheathing-derived cell line to study its attachment, morphology, and directionality</p><p>in neural regeneration. The less rigid and more amorphous topographies of PLA nano�ibers,</p><p>which are functionalized with different concentrations of a chemotactic agent, guided the mi-</p><p>gration of TEG3 cells toward more chemokine-concentrated surfaces better than the other</p><p>polymer scaffolds. It was observed that the size of the nano�ibers has a strong effect on TEG3</p><p>cell adhesion and migration; here, nano�ibers with 950 nm diameter showed highly dynamic</p><p>behavior in migratory terms. The roles of different nano�iber materials used in various tissue</p><p>regeneration applications are summarized in Table 2.</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/table/polymers-13-03746-t002/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 16/50</p><p>Table 2</p><p>Role of nano�iber materials in various tissue engineering applications.</p><p>Materials Property	and	Role Applications Ref.</p><p>Platelet-rich �ibrin loaded/chitosan core-</p><p>shell nano�ibrous scaffold</p><p>Helps in protecting and</p><p>preserving the</p><p>biomolecules from direct</p><p>contact with solvents and</p><p>changing</p><p>microenvironment during</p><p>in vitro studies</p><p>and in vivo</p><p>implantation.</p><p>Bone tissue</p><p>engineering</p><p>[124]</p><p>Polycaprolactone/polyvinylpyrrolidone</p><p>nano�ibers</p><p>Attachment and</p><p>proliferation of osteoblasts</p><p>in vitro while potentially</p><p>enhancing the cell–cell</p><p>interactions and cell</p><p>migration necessary for</p><p>bone healing</p><p>Bone regeneration [121]</p><p>Polylactic acid glycolic acid/silk �ibroin</p><p>membranes loaded with artemisinin</p><p>Polylactic acid glycolic</p><p>acid can provide good</p><p>mechanical properties, and</p><p>SF can improve the</p><p>biocompatibility and drug-</p><p>release property of</p><p>dressings. ART was loaded</p><p>on membranes as an anti-</p><p>in�lammatory agent</p><p>Wound dressing [130]</p><p>Poly-ε-caprolactone (PCL)/whitlockite (WH)</p><p>nano�iber membrane</p><p>This biomimetic nano�iber</p><p>membrane combines the</p><p>positive osteogenic</p><p>differentiation ability and</p><p>angiogenic ability of</p><p>calcium phosphate</p><p>materials, and is expected</p><p>to be used for arti�icial</p><p>periosteum.</p><p>Periosteal</p><p>Regeneration</p><p>[123]</p><p>Nano�iber alignment</p><p>played a supporting role on</p><p>cell alignment, with</p><p>parallel-oriented �ibers</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 17/50</p><p>3.1.3. Drug Delivery System A drug delivery system is a formulation that facilitates therapeutic</p><p>material to selectively reach the site of action without disrupting the functioning of other hu-</p><p>man body systems. Drugs are usually toxic when administered at the wrong doses. Hence, for</p><p>vital cases, customization is required, which cannot be provided with conventional medication</p><p>such as injections, pills, syrups, etc. Drug delivery through smaller-size suitable coating mate-</p><p>rial improves their capability to be digested or absorbed by the targeted site in a much feasible</p><p>manner. Electrospun �ibers with controllable material composition and structural properties</p><p>such as �iber diameter, geometry, and their �lexibility to be formulated in various shapes effect</p><p>the release pro�ile of bioactive molecules. These properties facilitate targeted and controlled</p><p>drug delivery [15,118]. The nano�ibers are also capable of encapsulating labile molecules for</p><p>rendered drug delivery by enhancing their stability in harsh biological environments [134].</p><p>A few of the current innovations in the �ield of drug delivery were detailed in this section.</p><p>Recently, Thao et al. [135] prepared an electrospun small intestinal submucosa (SIS) and</p><p>poly(caprolactone-co-Lactide-co-glycolide) (PCLA) nano�iber sheet, which acted as a potential</p><p>drug (dexamethasone and silver sulfadiazine) carrier related to anti-in�lammation (Figure 6a).</p><p>Here, amongst several synthetic polyesters, PCLA was chosen, as it offers several potential ad-</p><p>vantages like ease of preparation and better in vivo controllability due to biodegradable and</p><p>biocompatible properties. The ratio between SIS and PCLA was varied from 1:1 to 5:1 to ob-</p><p>tain various porosities (50% to 75%), pore size (ranged within 20–60 µm), �iber diameters</p><p>(ranging from 380 to 100 nm), and the tensile strength (ranged within 0.75 to 0.15 N) of the �i-</p><p>bers for optimized performance. The produced nano�iber sheet exhibited good biocompatible,</p><p>bioresorbable, and non-immunogenic properties. Sustained release of the drugs while sup-</p><p>pressing the macrophage in�iltration was ensured through in vitro and in vivo studies. In</p><p>another study, PVA/soy protein isolate (SPI) nano�iber mats were produced as drug carriers.</p><p>PVA is a nontoxic water-soluble polymer that shows high mechanical properties and good �ilm-</p><p>forming capability. It has been reported that SPI has been widely used in many biomedical ap-</p><p>plications, as it has the capability to decrease the proliferation of tumor cells and reduce the</p><p>activities of immunocompetent cells and bone-resorbing cells. Hence, for achieving synergic</p><p>properties, PVA/SPI nano�ibers were utilized in this study. The synthesized mats were loaded</p><p>with ketoprofen by dissolving the drug in the solutions for nano�iber during electrospinning.</p><p>To improve drug-release control of the nano�iber mats, a natural tubular nanoparticle named</p><p>sepiolite was utilized as a secondary release-control tool. Here, three types of nano�iber mats</p><p>were fabricated by direct mixing of PVA, SPI, and ketoprofen (average �iber diameter 137 nm;</p><p>speci�ic surface area 153.36 m /g); direct mixing of PVA, SPI, sepiolite, and ketoprofen (ave-</p><p>rage �iber diameter 117 nm; speci�ic surface area 168.24 m /g); and mixing PVA, SPI, and keto-</p><p>profen-preloaded sepiolite (average �iber diameter 129 nm; speci�ic surface area 194.27</p><p>m /g). Experiments showed that incorporation of SPI and sepiolite into the PVA nano�ibers in-</p><p>creased the mechanical strength of the mats up to 40%, making them long lasting and easier to</p><p>handle [136].</p><p>2</p><p>2</p><p>2</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f006/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 18/50</p><p>Figure 6</p><p>(a) Preparation and evaluation of drug-loaded nano�iber [135]. (b) Graphical representation of the fabrication</p><p>of scaffolds; preparation of antimicrobial agents/core–sheath nano�iber mats using coaxial electrospinning;</p><p>ef�icacy of single and multiple antimicrobial agents containing biphasic scaffolds against mixed-MRSA/P. ae-</p><p>ruginosa bio�ilms using different administration strategies [137].</p><p>A research team from the University of Nebraska fabricated biphasic scaffolds by integrating</p><p>nano�iber mats with dissolvable microneedle arrays (with 100 to 150 needles on a 6 mm disk)</p><p>through coaxial electrospinning for simultaneous drug delivery (Figure 6b). This type of</p><p>delivery system facilitates a complementary killing mechanism exhibiting synergistic ef�icacy.</p><p>This scaffold was reported as an antimicrobial delivery system for the effective treatment of</p><p>bacterial bio�ilms. In this study, polyvinylpyrrolidone (PVP) microneedle arrays and Pluronic F-</p><p>127-poly(ε-caprolactone) nano�iber mats were exploited with incorporation of different com-</p><p>binations of antimicrobial agents (AgNO, Ga(NO ) , and vancomycin) where a biphasic scaffold</p><p>served as the delivery agent for the eradication of mature bio�ilms on arti�icial wounds created</p><p>on ex vivo human skin explants [137].</p><p>A different study involved the production of dual drug delivery of vancomycin and</p><p>imipenem/cilastatin through core-shell nano�ibers composed of polyethylene oxide (PEO), chi-</p><p>tosan, PVP, and gelatin (with average �iber diameter varying from 218 to 342 nm) for the treat-</p><p>ment of diabetic foot ulcer infections. For such types of wounds, methicillin-resistant</p><p>Staphylococcus	aureus is one of the main sources of infection, which can be treated using com-</p><p>prehensive drugs like vancomycin and imipenem. For controlled drug delivery, these drugs can</p><p>be incorporated within the nano�iber matrix to reduce negative side effects and hazards like</p><p>nephrotoxicity, cytotoxicity, and hypersensitivity reaction. In this work, a dual drug-loaded na-</p><p>no�iber was prepared using PEO, CS, and vancomycin as shell materials and PVP, gelatin, and</p><p>imipenem/cilastatin as the core-forming matrix which can perform a simultaneous release of</p><p>vancomycin and imipenem at different rates into the wound sites. The results showed signi�i-</p><p>cant antibacterial activity against methicillin-resistant Staphylococcus	aureus, Escherichia	coli,</p><p>and Pseudomonas	aeruginosa with no recorded cytotoxicity [138].</p><p>Bai et al. [139] synthesized ibuprofen (IBU)-541 loaded PVP nano�ibers utilizing a coaxial so-</p><p>lid-core spinneret. IBU is a widely used drug for its anti-in�lammatory, analgesic, and</p><p>antipyretic properties. In this study, testing of fast dissolution of IBU from its electrospun</p><p>hydrophilic polymer nanocomposites was carried out. Here, the PVP nano�iber matrix was</p><p>chosen as drug carrier as it has a �ine physiological compatibility that does not have any stimu-</p><p>lation to skin, mucous membrane, eyes,</p><p>etc., and can act without interfering in the human meta-</p><p>bolism. These nano�ibers were observed to have an average diameter of 740 ± 130 nm with li-</p><p>near morphology, large surface cross-section, and porosity without any solid phase separation,</p><p>providing synergistic effects with an amorphous state of the drug. Liu et al. [140] fabricated bi-</p><p>functional copper sul�ide (CuS)/PVP/gelatin composite green synthesized nano�ibers by porta-</p><p>ble in situ electrospinning for rapid hemostasis and ablate super bacteria. CuS exhibited strong</p><p>absorption in NIR irradiation, which exerts an effective bactericidal effect on super bacteria.</p><p>3 3</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f006/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f006/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 19/50</p><p>However, it shows cytotoxicity which can be inhibited by incorporating it within a biodegrada-</p><p>ble and water-soluble polymer like gelatin and PVP, which helps in avoiding immediate contact</p><p>between CuS nanoparticles and cells. This composite �iber can be used to excite surface-plas-</p><p>mon effects that provide greater depth of penetration into the skin. It also effectively prevents</p><p>water superheating and skin damage caused by UV light. Here, nano�ibers were directly depo-</p><p>sited onto the wound to accelerate the hemostatic effect and improve the adhesion between</p><p>the membrane and skin. The nano�ibers with average diameter of 400 nm were produced on</p><p>the wound site and showed better compactness which facilitated the shortening of the overall</p><p>healing time by accelerating hemostasis to less than 6 s.</p><p>Precise drug delivery to tumor sites in cancer treatment is crucial for improved therapeutic</p><p>ef�icacy and minimizing adverse effects, which is an unmet clinical need [141]. Gastric cancer is</p><p>the third leading cause of death worldwide. Recently, to improve the chemotherapeutic perfor-</p><p>mance in gastric cancer, a study was carried out by Anothra and team [142]. To treat such a</p><p>cancer, 5-FU was extensively used in clinical practice. In this work, 5-FU loaded Eudragit S-100</p><p>composite nano�ibers (diameter ranging from 150–180 nm, porosity of 78%, and tensile</p><p>strength 170 g/cm ) were synthesized and optimized through a single-nozzle electrospinning</p><p>technique. Eudragit S-100 was chosen because of its polyanionic and biocompatible nature</p><p>which can exhibit controlled swelling in a gastric environment, providing customized drug rele-</p><p>ase. It is water insoluble, as well, as an acidic and is considered as a food-grade polymer due to</p><p>its non-toxicity. The developed system showed superior thermal stability, tumor regression po-</p><p>tential, and pharmacokinetic pro�ile when compared with the plain drug with 90% release of</p><p>encapsulated drug therapeutic after 12 h, making it a potential approach for localized treat-</p><p>ment of gastric cancer. The roles of different nano�iber materials used in various drug delivery</p><p>applications are summarized in Table 3.</p><p>2</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/table/polymers-13-03746-t003/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 20/50</p><p>Table 3</p><p>Role of nano�iber materials in various drug delivery applications.</p><p>Materials Property	and	Role Applications Ref.</p><p>Small intestine submucosa/poly(ε-</p><p>caprolactone-ran-L-lactide) Nano�iber</p><p>Sheets</p><p>Facilitated controlled drug delivery</p><p>related to anti-in�lammation</p><p>Drug</p><p>delivery</p><p>[135]</p><p>Poly (vinyl alcohol)/soy protein isolate</p><p>(PVA/SPI) nano�iber mats</p><p>The mats were loaded with</p><p>ketoprofen by dissolving the drug in</p><p>the solutions for nano�iber</p><p>electrospinning, providing</p><p>channelization.</p><p>Drug</p><p>delivery</p><p>[136]</p><p>Pluronic F-127-polycaprolactone</p><p>nano�iber mats</p><p>Nano�ibrous core helped in</p><p>encapsulating antimicrobial agents</p><p>with a hydrophilic nature</p><p>Drug</p><p>delivery</p><p>[137]</p><p>Ibuprofen (IBU)-loaded</p><p>polyvinylpyrrolidone nano�ibers</p><p>Concurred �ine functional</p><p>performances of electrospun</p><p>nano�ibers on improving the</p><p>dissolution of IBU</p><p>Drug</p><p>delivery</p><p>[139]</p><p>Thiram/hydroxypropyl-β-cyclodextrin</p><p>inclusion complex electrospun</p><p>nano�ibers</p><p>Improved the water solubility of</p><p>thiram</p><p>Drug</p><p>delivery</p><p>[143]</p><p>5-�luorouracil (5-FU) loaded Eudragit S-</p><p>100 composite nano�ibers</p><p>The developed nano�iber</p><p>formulation exhibited superior</p><p>tumor regression potential and</p><p>pharmacokinetic pro�ile compared</p><p>with the plain drug</p><p>Drug</p><p>delivery</p><p>[142]</p><p>Core-shell nano�ibrous system</p><p>containing vancomycin and</p><p>imipenem/cilastatin</p><p>The nano�ibers showed signi�icant</p><p>activity against both gram-positive</p><p>and negative bacteria, causing</p><p>diabetic foot ulcers.</p><p>Drug</p><p>delivery</p><p>[138]</p><p>Poly(vinyl alcohol) and chitosan</p><p>incorporated with moxi�loxacin</p><p>hydrochloride nano�ibers</p><p>Nano�ibers exhibited good</p><p>antibacterial properties against</p><p>Staphylococcus	aureus and</p><p>Pseudomonas	aeruginosa due to the</p><p>moxi�loxacin hydrochloride</p><p>incorporation.</p><p>Drug</p><p>delivery</p><p>[144]</p><p>Sulindac vinyl alcohol-co-ethylene</p><p>nano�iber membrane</p><p>Nano�iber membranes</p><p>demonstrated characteristics of</p><p>high drug loading and stability</p><p>Drug</p><p>delivery</p><p>[145]</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 21/50</p><p>3.1.4. Wound Dressing Wound dressing is a process of regenerating dermal and epidermal tis-</p><p>sues and a vital step for rapid healing of the affected part while offering protection against in-</p><p>fection due to environmental exposure. A number of biochemical actions/phases such as proli-</p><p>feration, homeostasis, in�lammation, and remodeling are involved in this dynamic activity</p><p>[146]. For these purposes, drug-embedded nano�ibers are potential substitutes in wound hea-</p><p>ling due to surface functionality, ability in inhibiting microorganism contact, oxy-permeability,</p><p>and lasting drug release [118,147]. As chronic wounds are prone to infection that might cause</p><p>sepsis and affect the overall healing process, studies have revealed that nano�ibers can offer</p><p>enhanced cell proliferation, migration, and angiogenesis for effective wound healing [148]. In</p><p>this regard, recently, lots of research has been carried out on multifunctional wound dressing,</p><p>which can provide all the requirements at a time for effective wound healing in order to boost</p><p>restoration within the wound site and prevent undesirable effects such as infection. In these</p><p>kinds of studies, nano�iber scaffolds are produced by blending various natural or synthetic</p><p>polymers and incorporating drugs, nanoparticles, and bioactive agents (as growth factors, vita-</p><p>mins, and anti-in�lammatory molecules) through the electrospinning process [149]. A few of</p><p>the recent works published on the bene�its of using electrospun nano�ibers in wound dressing</p><p>were summarized here.</p><p>Artemisia	annua L. is a type of annual herb that has been used for various treatments and</p><p>wound healing [150]. In their recent study, Peng and team [130] utilized Artemisinin (ART), a</p><p>sesquiterpene lactone compound with therapeutic properties like anti-in�lammatory and anti-</p><p>bacterial activity, to evaluate in vivo wound healing in a rat model with dorsal full-thickness</p><p>wound defects. Polylactic acid glycolic acid (PLGA)/silk �ibroin (SF) membranes loaded with</p><p>ART composite nano�ibrous membranes were electrospun for this study. PLGA NFMs is a bio-</p><p>degradable polymer with good mechanical properties along with controlled degradability and</p><p>drug release quality, which are necessary in biomedical applications. However, there are some</p><p>drawbacks like poor hydrophilicity and cell af�inity which can be improved by combining it</p><p>with natural polymers like SF. SF, a Bombyx	mori cocoon extract, has good cytocompatibility</p><p>and biocompatibility in both in vivo or in vitro applications.</p><p>SF possesses attractive characteris-</p><p>tics such as cell adhesion and proliferation that promotes wound healing. The fabricated mem-</p><p>brane showed breaking strength ranging from 4.0 ± 1.0 MPa to 7.4 ± 0.3 MPa and Young’s mo-</p><p>dulus from 215.3 ± 2.0 MPa to 394.9 ± 1.3 MPa with elongation at break from 34.0 ± 7.8% to</p><p>127.0 ± 7.0%. The study proved that the obtained mechanical and anti-in�lammatory property</p><p>was suitable for wound dressing, without cytotoxicity. This provided a new method for the de-</p><p>velopment and application of ART for wound healing.</p><p>Chronic wounds, such as diabetic ulcers and burns, are complex wounds with slow healing ra-</p><p>tes, and when left untreated for longer periods of time become fatal and may result in hospita-</p><p>lization. In such cases, Blumea	balsamifera (BB), which is also known as “Sambong”, is one of</p><p>the essential oils which have been used for thousands of years in Southeast Asian countries.</p><p>Ullah et al. [151] prepared ultra�ine, bead-free, bioactive sambong oil-loaded electrospun cellu-</p><p>lose acetate nano�ibers for wound dressing applications. The as-synthesized �ibrous materials</p><p>exhibited in-vitro biocompatibility, cell viability, breathability (moisture vapor transport rate of</p><p>2450–1750 g/m /day), and good antibacterial and antioxidant properties. The inclusion of BB</p><p>oil resulted in a decrease in tensile strength and increase in �iber diameter, reducing porosity</p><p>of the materials. They were also observed to undergo �irst-order release kinetics immediately</p><p>after biphasic release. Cipro�loxacin is another well-known antibacterial drug that has been uti-</p><p>lized for healing a wide range of wound infections. A study involving in vitro and in vivo evalu-</p><p>ations of cipro�loxacin (antibacterial drug)-loaded chitosan/polyethylene oxide/silica nano�i-</p><p>2</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 22/50</p><p>bers fabrication through electrospinning for treating cutaneous wounds of Balb/C mice was</p><p>carried out by Hashemikia and coworkers (Figure 7a). It was noticed that �ibers’ structural</p><p>integrity was intact for more than 7 days in the phosphate buffer saline, while demonstrating</p><p>excellent antibacterial properties. The synthesized nano�iber scaffold was able to absorb water</p><p>while maintaining morphological integrity during drug release and degradation processes. It</p><p>was observed here that silica played a crucial role in collagen creation, accelerating the wound-</p><p>healing process through degradation products of silica-materials [152].</p><p>Figure 7</p><p>(a) Interactions of the inorganic framework with chitosan and polyethylene oxide; SEM images, �ibers size</p><p>distribution, EDX and X-ray mapping [152]. (b) Schematic Illustration of fabrication process of nano�iber</p><p>scaffolds; concentration of hemoglobin in blood clots on scaffolds; blood clotting time and blood absorption</p><p>capacity of the medical gauze control and PCLM, CSLD, and CSLD-PCLM nano�iber scaffolds * p < 0.05, ** p <</p><p>0.01 [155].</p><p>Annatto is a natural dye obtained from tropical plants and is mainly studied for its anti-</p><p>in�lammatory, antioxidant, antimicrobial, and anti-cancer activity and potential applications in</p><p>the �ields of wound healing and tissue engineering. A study was conducted by Santos et al. to</p><p>explore wound healing ef�icacy, �ibroblast cellular proliferation, and in vitro cytotoxicity by</p><p>evaluating annatto functionalized cellulose acetate nano�iber scaffolds in a rat model. Here, the</p><p>bioactive molecule included in the nano�iber and �ibroblast cells was attached and penetrated</p><p>to modulate the in vivo in�lammatory process favorably. In the analysis, cytotoxicity found no</p><p>irritation produced in hen’s egg-chorioallantois membrane test assays, which veri�ied</p><p>biocompatibility. It was observed to be viable in mouse �ibroblasts even after 48 h of culture</p><p>[153]. Mupirocin is an antibacterial agent that effectively reacts with the pathogens and treats</p><p>various topical wounds like burns and foot ulcers [154]. Yang et al. [155] worked on designing</p><p>multifunctional lidocaine hydrochloride (LID) and mupirocin-loaded</p><p>chitosan/polycaprolactone (CSLD-PCLM) scaffolds using dual spinneret electrospinning and</p><p>studied its varied dual drug release capability (Figure 7b). Nano�ibrous scaffolds showed rapid</p><p>release of LID, sustained release of mupirocin, and enhanced interfacial interaction with blood</p><p>cells while possessing blood coagulation capacity. Re-epithelialization along with collagen de-</p><p>position in the skin defect model of rat was also reported.</p><p>Melatonin is a hormone that exhibits positive effects on wound healing. It possesses abilities</p><p>such as stimulation of �ibroblasts, epithelial cell proliferation, and growth factors for collagen</p><p>�ibers formation [156]. A three-layer chitosan-polycaprolactone/polyvinylalcohol</p><p>melatonin/chitosan-polycaprolactone wound dressing loaded with melatonin was fabricated</p><p>by Minmajidi and group [157] to obtain 45% reduced burst release and sustained melatonin</p><p>release for 11 days. The scaffold was tested on a full-thickness excisional model of rat skin by</p><p>the local administration of the drug. During a similar timeline, Saatchi et al. [158] studied �ive</p><p>different electrospun chitosan-based scaffolds with a wide range of cerium-doped bioactive</p><p>glass-loaded chitosan/polyethylene oxide nano�iber ratio for wound-healing applications. In-</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f007/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f007/</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/figure/polymers-13-03746-f007/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 23/50</p><p>creasing the content of cerium doped bioactive glass enhanced the swelling degree and mecha-</p><p>nical properties (break elongation 28.6%) of the scaffolds. The roles of different nano�iber ma-</p><p>terials used in various wound dressing applications are summarized in Table 4.</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/table/polymers-13-03746-t004/</p><p>02/02/2023 12:19 Uma revisão sobre aplicações avançadas baseadas em nanofibras eletrofiadas: de cuidados de saúde a dispositivos de ene…</p><p>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587893/ 24/50</p><p>Table 4</p><p>Role of nano�iber materials in various wound-dressing applications.</p><p>Materials Property	and	Role Applications Ref.</p><p>Blumea	balsamifera oil loaded cellulose</p><p>acetate nano�iber mats</p><p>The oil loaded nano�iber mats</p><p>showed good antibacterial</p><p>ef�icacy against the E.	coli and</p><p>S.	aureus in agar disc diffusion</p><p>and OD (bactericidal effect</p><p>with time-dependence) tests</p><p>Wound</p><p>dressing</p><p>[151]</p><p>cipro�loxacin-loaded chitosan/polyethylene</p><p>oxide/silica nano�ibers</p><p>For the �irst time, this hybrid</p><p>organic/inorganic material was</p><p>introduced for wound dressing</p><p>and the in vitro and in vivo</p><p>preclinical examination of the</p><p>prepared nano�iber.</p><p>Wound</p><p>dressing</p><p>[152]</p><p>Cellulose acetate/annatto extract nano�ibers</p><p>(CA/annatto)</p><p>Cellulose acetate nano�ibers</p><p>containing crude annatto</p><p>extract potential for biomedical</p><p>applications</p><p>Wound</p><p>dressing</p><p>[153]</p><p>Lidocaine hydrochloride (LID) and</p><p>mupirocin-loaded chitosan/polycaprolactone</p><p>(CSLD-PCLM) Nano�iber scaffolds</p><p>The nano�iber structure</p><p>enhanced the interfacial</p><p>interaction between the</p><p>scaffold and blood cells</p><p>Wound</p><p>dressing</p><p>[155]</p><p>Cerium-doped bioactive glass-loaded</p><p>chitosan/polyethylene oxide nano�iber</p><p>Scaffold in its wet state had</p><p>mechanical properties very</p><p>close to the skin and its</p><p>elongation at break was 28.6%,</p><p>which was only 20% less than</p><p>the required elongation at</p><p>break for skin tissue scaffolds.</p><p>Wound</p><p>dressing</p><p>[158]</p><p>Curcumin loaded</p><p>polycaprolactone-/polyvinyl alcohol-silk</p><p>�ibroin nano�ibers mat</p><p>Polycaprolactone and</p><p>polyvinyl alcohol helped to</p><p>strengthen the nano�iber</p><p>Wound</p><p>dressing</p><p>[159]</p><p>Chitosan -polycaprolactone/polyvinylalcohol</p>