nanofiber

Nanofibers were first produced via electrospinning more than four centuries ago.{{cite journal | vauthors = Nascimento ML, Araújo ES, Cordeiro ER, de Oliveira AH, de Oliveira HP | title = A Literature Investigation about Electrospinning and Nanofibers: Historical Trends, Current Status and Future Challenges | journal = Recent Patents on Nanotechnology | volume = 9 | issue = 2 | pages = 76–85 | date = 2015 | pmid = 27009122 | doi = 10.2174/187221050902150819151532 }}{{cite journal| vauthors = Tucker N, Stanger JJ, Staiger MP, Razzaq H, Hofman K |title=The history of the science and technology of electrospinning from 1600 to 1995|journal=J Eng Fibers Fabr|date=2012|volume=7|pages=63–73|url=http://www.jeffjournal.org/papers/Volume7/7.2b.10N.Tucker.pdf}} Beginning with the development of the electrospinning method, English physicist William Gilbert (1544-1603) first documented the electrostatic attraction between liquids by preparing an experiment in which he observed a spherical water drop on a dry surface warp into a cone shape when it was held below an electrically charged amber.{{cite journal|last1=Gilbert|first1=William | name-list-style = vanc |title=De magnete, magneticisque corporibus, et de magno magnete tellure|date=1600}} This deformation later came to be known as the Taylor cone.{{cite journal| vauthors = Taylor G |title=Disintegration of water drops in an electric field|journal=Proceedings of the Royal Society A|date=1964|volume=280|issue=1382|pages=383–39 7|doi=10.1098/rspa.1964.0151|bibcode=1964RSPSA.280..383T |s2cid=15067908}} In 1882, English physicist Lord Rayleigh (1842-1919) analyzed the unstable states of liquid droplets that were electrically charged, and noted that the liquid was ejected in tiny jets when equilibrium was established between the surface tension and electrostatic force.{{cite journal| vauthors = Strutt J |title=On the equilibrium of liquid conducting masses charged with electricity London, Edinburgh, and Dublin|journal=Philos. Mag.|date=1882|volume=14|issue=87|pages=184–186|doi=10.1080/14786448208628425|url=https://zenodo.org/record/1431159}} In 1887, British physicist Charles Vernon Boys (1855-1944) published a manuscript about nanofiber development and production.{{cite journal| vauthors = Boys C |title=On the production, properties, and some suggested uses of the finest threads|journal=Philos. Mag.|date=1887|volume=23|issue=145|pages=489–499|doi=10.1080/14786448708628043|url=https://zenodo.org/record/1431177}} In 1900, American inventor John Francis Cooley (1861-1903) filed the first modern electrospinning patent.{{cite web| vauthors = Cooley J |title=Improved methods of and apparatus for electrically separating the relatively volatile liquid component from the component of relatively fixed substances of composite fluids|url=https://worldwide.espacenet.com/publicationDetails/biblio?CC=GB&NR=190006385|website=Espacenet}}

Anton Formhals was the first person to attempt nanofiber production between 1934 and 1944 and publish the first patent describing the experimental production of nanofibers. In 1966, Harold Simons published a patent for a device that could produce thin and light nanofiber fabrics with diverse motifs.{{cite web|last1=Harold|first1=Simon | name-list-style = vanc |title=Process and apparatus for producing patterned non-woven fabrics|url=https://worldwide.espacenet.com/publicationDetails/biblio?CC=US&NR=3280229A&KC=A&FT=D|website=Espacenet}}

Only at the end of the 20th century have the words electrospinning and nanofiber become common language among scientists and researchers. Electrospinning continues to be developed today.

Many chemical and mechanical techniques for preparing nanofibers exist.

{{main|Electrospinning}}

File:Electrospinning Image for Wikipedia.tif

File:Taylor cone.jpg

Electrospinning is the most commonly used method to fabricate nanofibers.{{cite journal | vauthors = Lolla D, Gorse J, Kisielowski C, Miao J, Taylor PL, Chase GG, Reneker DH | title = Polyvinylidene fluoride molecules in nanofibers, imaged at atomic scale by aberration corrected electron microscopy | journal = Nanoscale | volume = 8 | issue = 1 | pages = 120–8 | date = January 2016 | pmid = 26369731 | doi = 10.1039/C5NR01619C | url = http://www.escholarship.org/uc/item/1fp5d847 | bibcode = 2015Nanos...8..120L | s2cid = 205976678 }}

{{cite journal | vauthors = Sarbatly R, Krishnaiah D, Kamin Z | title = A review of polymer nanofibres by electrospinning and their application in oil-water separation for cleaning up marine oil spills | journal = Marine Pollution Bulletin | volume = 106 | issue = 1–2 | pages = 8–16 | date = May 2016 | pmid = 27016959 | doi = 10.1016/j.marpolbul.2016.03.037 | bibcode = 2016MarPB.106....8S | name-list-style = amp }}{{Cite journal|last1=Sivan|first1=Manikandan|last2=Madheswaran|first2=Divyabharathi|last3=Asadian|first3=Mahtab|last4=Cools|first4=Pieter|last5=Thukkaram|first5=Monica|last6=Van Der Voort|first6=Pascal|last7=Morent|first7=Rino|last8=De Geyter|first8=Nathalie|last9=Lukas|first9=David | name-list-style = vanc |date=2020-10-15|title=Plasma treatment effects on bulk properties of polycaprolactone nanofibrous mats fabricated by uncommon AC electrospinning: A comparative study|url=http://www.sciencedirect.com/science/article/pii/S0257897220308720|journal=Surface and Coatings Technology|language=en|volume=399|pages=126203|doi=10.1016/j.surfcoat.2020.126203|s2cid=224924026|issn=0257-8972}}{{Cite journal|last1=Madheswaran|first1=Divyabharathi|last2=Sivan|first2=Manikandan|last3=Valtera|first3=Jan|last4=Kostakova|first4=Eva Kuzelova|last5=Egghe|first5=Tim|last6=Asadian|first6=Mahtab|last7=Novotny|first7=Vit|last8=Nguyen|first8=Nhung H. A.|last9=Sevcu|first9=Alena|last10=Morent|first10=Rino|last11=Geyter|first11=Nathalie De|title=Composite yarns with antibacterial nanofibrous sheaths produced by collectorless alternating-current electrospinning for suture applications|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/app.51851|journal=Journal of Applied Polymer Science|year=2022|volume=139|issue=13|language=en|pages=51851|doi=10.1002/app.51851|s2cid=243969095|issn=1097-4628}}{{Cite journal|last1=Manikandan|first1=S.|last2=Divyabharathi|first2=M.|last3=Tomas|first3=K.|last4=Pavel|first4=P.|last5=David|first5=L.|date=2019-01-01|title=Production of poly (ε-caprolactone) Antimicrobial Nanofibers by Needleless Alternating Current Electrospinning|url=https://www.sciencedirect.com/science/article/pii/S221478531931898X|journal=Materials Today: Proceedings|series=6th International Conference on Recent Advances in Materials, Minerals & Environment (RAMM) 2018, RAMM 2018, 27–29 November 2018, Penang, Malaysia|language=en|volume=17|pages=1100–1104|doi=10.1016/j.matpr.2019.06.526|s2cid=202207593|issn=2214-7853}}

The instruments necessary for electrospinning include a high voltage supplier, a capillary tube with a pipette or needle with a small diameter, and a metal collecting screen. One electrode is placed into the polymer solution and the other electrode is attached to the collector. An electric field is applied to the end of the capillary tube that contains the polymer solution held by its surface tension and forms a charge on the surface of the liquid. As the intensity of the electric field increases, the hemispherical surface of the fluid at the tip of the capillary tube elongates to form a conical shape known as the Taylor cone. A critical value is attained upon further increase in the electric field in which the repulsive electrostatic force overcomes the surface tension and the charged jet of fluid is ejected from the tip of the Taylor cone. The discharged polymer solution jet is unstable and elongates as a result, allowing the jet to become very long and thin. Charged polymer fibers solidifies with solvent evaporation.{{cite journal | vauthors = Garg K, Bowlin GL | title = Electrospinning jets and nanofibrous structures | journal = Biomicrofluidics | volume = 5 | issue = 1 | pages = 13403 | date = March 2011 | pmid = 21522493 | pmc = 3082340 | doi = 10.1063/1.3567097 }} Randomly-oriented nanofibers are collected on the collector. Nanofibers can also be collected in a highly aligned fashion by using specialized collectors such as the rotating drum,{{cite journal| vauthors = Kim KW, Lee KH, Khil MS, Ho YS, Kim HY |title=The effect of molecular weight and the linear velocity of drum surface on the properties of electrospun poly(ethylene terephthalate) nonwovens|journal=Fibers Polym|date=2004|volume=5|issue=2|pages=122–127|doi=10.1007/BF02902925|s2cid=137021572}} metal frame,{{cite journal| vauthors = Dersch R, Liu T, Schaper AK, Greiner A, Wendorff JH |title=Electrospun nanofibers: internal structure and intrinsic orientation|journal=Polym Chem|date=2003|volume=41|issue=4|pages=545–553|doi=10.1002/pola.10609|bibcode=2003JPoSA..41..545D}} or a two-parallel plates system.{{cite journal | vauthors = Beachley V, Wen X | title = Effect of electrospinning parameters on the nanofiber diameter and length | journal = Materials Science & Engineering. C, Materials for Biological Applications | volume = 29 | issue = 3 | pages = 663–668 | date = April 2009 | pmid = 21461344 | pmc = 3065832 | doi = 10.1016/j.msec.2008.10.037 }} Parameters such as jet stream movement and polymer concentration have to be controlled to produce nanofibers with uniform diameters and morphologies.{{cite journal | vauthors = Leach MK, Feng ZQ, Tuck SJ, Corey JM | title = Electrospinning fundamentals: optimizing solution and apparatus parameters | journal = Journal of Visualized Experiments | volume = 47 | issue = 47 | page = 2494 | date = January 2011 | pmid = 21304466 | pmc = 3182658 | doi = 10.3791/2494 }}

The electrospinning technique transforms many types of polymers into nanofibers. An electrospun nanofiber network resembles the extracellular matrix (ECM) well.{{cite journal| vauthors = Huang ZM, Zhang YZ, Kotaki M, Ramakrishna S |title=A review on polymer nanofibers by electrospinning and their applications in nanocomposites|journal=Compos Sci Technol|date=2003|volume=63|issue=15|pages=2223–2253|doi=10.1016/S0266-3538(03)00178-7|s2cid=4511766 }}{{cite journal | vauthors = Cheng J, Jun Y, Qin J, Lee SH | title = Electrospinning versus microfluidic spinning of functional fibers for biomedical applications | journal = Biomaterials | volume = 114 | pages = 121–143 | date = January 2017 | pmid = 27880892 | doi = 10.1016/j.biomaterials.2016.10.040 }} This resemblance is a major advantage of electrospinning because it opens up the possibility of mimicking the ECM with regards to fiber diameters, high porosity, and mechanical properties. Electrospinning is being further developed for mass production of one-by-one continuous nanofibers.

Thermal-induced phase separation separates a homogenous polymer solution into a multi-phase system via thermodynamic changes.{{cite journal | vauthors = Ma PX, Zhang R | title = Synthetic nano-scale fibrous extracellular matrix | journal = Journal of Biomedical Materials Research | volume = 46 | issue = 1 | pages = 60–72 | date = July 1999 | pmid = 10357136 | doi = 10.1002/(sici)1097-4636(199907)46:1<60::aid-jbm7>3.0.co;2-h | hdl-access = free | hdl = 2027.42/34415 }}{{cite journal|last1=Ma|first1=P.|title=Scaffolds for tissue fabrication|journal=Materials Today|date=2004|volume=7|issue=5|pages=30–40|doi=10.1016/S1369-7021(04)00233-0|doi-access=free}} The procedure involves five steps: polymer dissolution, liquid-liquid or liquid-solid phase separation, polymer gelation, extraction of solvent from the gel with water, and freezing and freeze-drying under vacuum. Thermal-induced phase separation method is widely used to generate scaffolds for tissue regeneration.

The homogenous polymer solution in the first step is thermodynamically unstable and tends to separate into polymer-rich and polymer-lean phases under appropriate temperature. Eventually after solvent removal, the polymer-rich phase solidifies to form the matrix and the polymer-lean phase develops into pores.{{Citation needed|date=December 2019|reason=removed citation to predatory publisher content}} Next, two types of phase separation can be carried out on the polymer solution depending on the desired pattern. Liquid-liquid separation is usually used to form bicontinuous phase structures while solid-liquid phase separation is used to form crystal structures. The gelation step plays a crucial role in controlling the porous morphology of the nanofibrous matrices. Gelation is influenced by temperature, polymer concentration, and solvent properties. Temperature regulates the structure of the fiber network: low gelation temperature results in formation of nanoscale fiber networks while high gelation temperature leads to the formation of a platelet-like structure. Polymer concentration affects fiber properties: an increase in polymer concentration decreases porosity and increases mechanical properties such as tensile strength. Solvent properties influence morphology of the scaffolds. After gelation, gel is placed in distilled water for solvent exchange. Afterwards, the gel is removed from the water and goes through freezing and freeze-drying. It is then stored in a desiccator until characterization.

The drawing method makes long single strands of nanofibers one at a time. The pulling process is accompanied by solidification that converts the dissolved spinning material into a solid fiber.{{cite book| vauthors = Ramakrishna S |display-authors=etal|title=An Introduction to Electrospinning and Nanofibers|date=2005|publisher=World Scientific|isbn=978-981-256-415-3}} A cooling step is necessary in the case of melt spinning and evaporation of solvent in the case of dry spinning. A limitation, however, is that only a viscoelastic material that can undergo extensive deformations while possessing sufficient cohesion to survive the stresses developed during pulling can be made into nanofibers through this process.{{cite journal| vauthors = Ondarcuhu T, Joachim C |title=Drawing a single nanofiber over hundreds of microns|journal=Europhys Lett|date=1998|volume=42|issue=2|pages=215–220|doi=10.1209/epl/i1998-00233-9|bibcode=1998EL.....42..215O|s2cid=250737386 }}

The template synthesis method uses a nanoporous membrane template composed of cylindrical pores of uniform diameter to make fibrils (solid nanofiber) and tubules (hollow nanofiber).{{cite journal| vauthors = Martin C |title=Template synthesis of electronically conductive polymer nanostructures|journal=Acc Chem Res|date=1995|volume=28|issue=2|pages=61–68|doi=10.1021/ar00050a002}}{{cite journal | vauthors = Martin CR | title = Nanomaterials: a membrane-based synthetic approach | journal = Science | volume = 266 | issue = 5193 | pages = 1961–6 | date = December 1994 | pmid = 17836514 | doi = 10.1126/science.266.5193.1961 | s2cid = 45456343 | bibcode = 1994Sci...266.1961M }} This method can be used to prepare fibrils and tubules of many types of materials, including metals, semiconductors and electronically conductive polymers. The uniform pores allow for control of the dimensions of the fibers so nanofibers with very small diameters can be produced through this method. However, a drawback of this method is that it cannot make continuous nanofibers one at a time.

The self-assembly technique is used to generate peptide nanofibers and peptide amphiphiles. The method was inspired by the natural folding process of amino acid residues to form proteins with unique three-dimensional structures.{{cite journal | vauthors = Malkar NB, Lauer-Fields JL, Juska D, Fields GB | title = Characterization of peptide-amphiphiles possessing cellular activation sequences | journal = Biomacromolecules | volume = 4 | issue = 3 | pages = 518–28 | date = 2003 | pmid = 12741765 | doi = 10.1021/bm0256597 }} The self-assembly process of peptide nanofibers involves various driving forces such as hydrophobic interactions, electrostatic forces, hydrogen bonding and van der Waals forces and is influenced by external conditions such as ionic strength and pH.{{cite journal | vauthors = Zhang C, Xue X, Luo Q, Li Y, Yang K, Zhuang X, Jiang Y, Zhang J, Liu J, Zou G, Liang XJ | display-authors = 6 | title = Self-assembled Peptide nanofibers designed as biological enzymes for catalyzing ester hydrolysis | journal = ACS Nano | volume = 8 | issue = 11 | pages = 11715–23 | date = November 2014 | pmid = 25375351 | doi = 10.1021/nn5051344 }}

File:Dense connective tissue-400x.jpg

Due to their high porosity and large surface area-to-volume ratio, nanofibers are widely used to construct scaffolds for biological applications. Major examples of natural polymers used in scaffold production are collagen, cellulose, silk fibroin, keratin, gelatin and polysaccharides such as chitosan and alginate. Collagen is a natural extracellular component of many connective tissues. Its fibrillary structure, which varies in diameter from 50-500 nm, is important for cell recognition, attachment, proliferation and differentiation. Using type I collagen nanofibers produced via electrospinning, Shih et al. found that the engineered collagen scaffold showed an increase in cell adhesion and decrease in cell migration with increasing fiber diameter.{{cite journal | vauthors = Shih YR, Chen CN, Tsai SW, Wang YJ, Lee OK | title = Growth of mesenchymal stem cells on electrospun type I collagen nanofibers | journal = Stem Cells | volume = 24 | issue = 11 | pages = 2391–7 | date = November 2006 | pmid = 17071856 | doi = 10.1634/stemcells.2006-0253 | doi-access = free }} Using silk scaffolds as a guide for growth for bone tissue regeneration, Kim et al. observed complete bone union after 8 weeks and complete healing of defects after 12 weeks whereas the control in which the bone did not have the scaffold displayed limited mending of defects in the same time period.{{cite journal | vauthors = Kim KH, Jeong L, Park HN, Shin SY, Park WH, Lee SC, Kim TI, Park YJ, Seol YJ, Lee YM, Ku Y, Rhyu IC, Han SB, Chung CP | display-authors = 6 | title = Biological efficacy of silk fibroin nanofiber membranes for guided bone regeneration | journal = Journal of Biotechnology | volume = 120 | issue = 3 | pages = 327–39 | date = November 2005 | pmid = 16150508 | doi = 10.1016/j.jbiotec.2005.06.033 }} Similarly, keratin, gelatin, chitosan and alginate demonstrate excellent biocompatibility and bioactivity in scaffolds.

However, cellular recognition of natural polymers can easily initiate an immune response. Consequently, synthetic polymers such as poly(lactic acid) (PLA), polycaprolactone (PCL), polyurethane (PU), poly(lactic-co-glycolic acid) (PLGA), poly(L-lactide) (PLLA), and poly(ethylene-co-vinylacetate) (PEVA) have been developed as alternatives for integration into scaffolds. Being biodegradable and biocompatible, these synthetic polymers can be used to form matrices with a fiber diameter within the nanometer range. Out of these synthetic polymers, PCL has generated considerable enthusiasm among researchers.{{cite journal| vauthors = Azimi B, Nourpanah P, Rabiee M, Arbab S |title=Poly (ε-caprolactone) fiber: an overview|journal=J Eng Fibers Fabr|date=2014|volume=9|issue=3|pages=74–90}} PCL is a type of biodegradable polyester that can be prepared via ring-opening polymerization of ε-caprolactone using catalysts. It shows low toxicity, low cost and slow degradation. PCL can be combined with other materials such as gelatin, collagen, chitosan, and calcium phosphate to improve the differentiation and proliferation capacity (2, 17). PLLA is another popular synthetic polymer. PLLA is well known for its superior mechanical properties, biodegradability and biocompatibility. It shows efficient cell migration ability due to its high spatial interconnectivity, high porosity and controlled alignment.{{cite journal | vauthors = Hejazi F, Mirzadeh H | title = Novel 3D scaffold with enhanced physical and cell response properties for bone tissue regeneration, fabricated by patterned electrospinning/electrospraying | journal = Journal of Materials Science. Materials in Medicine | volume = 27 | issue = 9 | pages = 143 | date = September 2016 | pmid = 27550014 | doi = 10.1007/s10856-016-5748-8 | s2cid = 23987237 }} A blend of PLLA and PLGA scaffold matrix has shown proper biomimetic structure, good mechanical strength and favorable bioactivity.

File:Woven bone matrix.jpg

In tissue engineering, a highly porous artificial extracellular matrix is needed to support and guide cell growth and tissue regeneration.{{cite journal | vauthors = Burg KJ, Porter S, Kellam JF | title = Biomaterial developments for bone tissue engineering | journal = Biomaterials | volume = 21 | issue = 23 | pages = 2347–59 | date = December 2000 | pmid = 11055282 | doi = 10.1016/s0142-9612(00)00102-2 }}{{cite journal| vauthors = Sun B, Long YZ, Zhang HD, Li MM, Duvail JL, Jiang XY, Yin HL |title=Advances in three-dimensional nanofibrous macrostructures via electrospinning|journal=Prog Polym Sci|date=2014|volume=39|issue=5|pages=862–890|doi=10.1016/j.progpolymsci.2013.06.002}} Natural and synthetic biodegradable polymers have been used to create such scaffolds.

Simon, in a 1988 NIH SBIR grant report, showed that electrospinning could be used to produce nano- and submicron-scale polystyrene and polycarbonate fibrous mats specifically intended for use as in vitro cell substrates. This early use of electrospun fibrous lattices for cell culture and tissue engineering showed that Human Foreskin Fibroblasts (HFF), transformed Human Carcinoma (HEp-2), and Mink Lung Epithelium (MLE) would adhere to and proliferate upon the fibers.{{Cite web|url=https://www.researchgate.net/publication/317053872|title=NIH PHASE I FINAL REPORT: FIBROUS SUBSTRATES FOR CELL CULTURE (R3RR03544A) (PDF Download Available)|last=Simon|first=Eric M.|date=1988|website=ResearchGate|language=en|access-date=2017-05-22}}{{Cite journal|last1=Sukumar|first1=Uday Kumar|last2=Packirisamy|first2=Gopinath | name-list-style = vanc |date=2019-10-08|title=Fabrication of Nanofibrous Scaffold Grafted with Gelatin Functionalized Polystyrene Microspheres for Manifesting Nanomechanical Cues of Stretch Stimulated Fibroblast|journal=ACS Applied Bio Materials|volume=2|issue=12|pages=5323–5339|doi=10.1021/acsabm.9b00580|pmid=35021533|s2cid=208733153}}

Nanofiber scaffolds are used in bone tissue engineering to mimic the natural extracellular matrix of the bones. The bone tissue is arranged either in a compact or trabecular pattern and composed of organized structures that vary in length from the centimeter range all the way to the nanometer scale. Nonmineralized organic component (i.e. type 1 collagen), mineralized inorganic component (i.e. hydroxyapatite), and many other noncollagenous matrix proteins (i.e. glycoproteins and proteoglycans) make up the nanocomposite structure of the bone ECM. The organic collagen fibers and the inorganic mineral salts provide flexibility and toughness, respectively, to ECM.

Although the bone is a dynamic tissue that can self-heal upon minor injuries, it cannot regenerate after experiencing large defects such as bone tumor resections and severe nonunion fractures because it lacks the appropriate template. Currently, the standard treatment is autografting which involves obtaining the donor bone from a non-significant and easily accessible site (i.e. iliac crest) in the patient own body and transplanting it into the defective site. Transplantation of autologous bone has the best clinical outcome because it integrates reliably with the host bone and can avoid complications with the immune system.{{cite journal | vauthors = Betz RR | title = Limitations of autograft and allograft: new synthetic solutions | journal = Orthopedics | volume = 25 | issue = 5 Suppl | pages = s561-70 | date = May 2002 | pmid = 12038843 | doi = 10.3928/0147-7447-20020502-04 }} But its use is limited by its short supply and donor site morbidity associated with the harvest procedure. Furthermore, autografted bones are avascular and hence are dependent on diffusion for nutrients, which affects their viability in the host. The grafts can also be resorbed before osteogenesis is complete due to high remodeling rates in the body. Another strategy for treating severe bone damage is allografting which transplants bones harvested from a human cadaver. However, allografts introduce the risk of disease and infection in the host.

Bone tissue engineering presents a versatile response to treat bone injuries and deformations. Nanofibers produced via electrospinning mimics the architecture and characteristics of natural extracellular matrix particularly well. These scaffolds can be used to deliver bioactive agents that promote tissue regeneration. These bioactive materials should ideally be osteoinductive, osteoconductive, and osseointegratable. Bone substitute materials intended to replace autologous or allogeneic bone consist of bioactive ceramics, bioactive glasses, and biological and synthetic polymers. The basis of bone tissue engineering is that the materials will be resorbed and replaced over time by the body’s own newly regenerated biological tissue.

Tissue engineering is not only limited to the bone: a large amount of research is devoted to cartilage,{{cite journal | vauthors = Tuli R, Li WJ, Tuan RS | title = Current state of cartilage tissue engineering | journal = Arthritis Research & Therapy | volume = 5 | issue = 5 | pages = 235–8 | date = 2003 | pmid = 12932283 | pmc = 193737 | doi = 10.1186/ar991 | doi-access = free }} ligament,{{cite journal | vauthors = Lin VS, Lee MC, O'Neal S, McKean J, Sung KL | title = Ligament tissue engineering using synthetic biodegradable fiber scaffolds | journal = Tissue Engineering | volume = 5 | issue = 5 | pages = 443–52 | date = October 1999 | pmid = 10586100 | doi = 10.1089/ten.1999.5.443 }} skeletal muscle,{{cite journal | vauthors = Riboldi SA, Sampaolesi M, Neuenschwander P, Cossu G, Mantero S | title = Electrospun degradable polyesterurethane membranes: potential scaffolds for skeletal muscle tissue engineering | journal = Biomaterials | volume = 26 | issue = 22 | pages = 4606–15 | date = August 2005 | pmid = 15722130 | doi = 10.1016/j.biomaterials.2004.11.035 | url = https://lirias.kuleuven.be/handle/123456789/187554 }} skin,{{cite journal | vauthors = Matthews JA, Wnek GE, Simpson DG, Bowlin GL | title = Electrospinning of collagen nanofibers | journal = Biomacromolecules | volume = 3 | issue = 2 | pages = 232–8 | date = 2002 | pmid = 11888306 | doi = 10.1021/bm015533u }} blood vessel,{{cite journal | vauthors = Mo XM, Xu CY, Kotaki M, Ramakrishna S | title = Electrospun P(LLA-CL) nanofiber: a biomimetic extracellular matrix for smooth muscle cell and endothelial cell proliferation | journal = Biomaterials | volume = 25 | issue = 10 | pages = 1883–90 | date = May 2004 | pmid = 14738852 | doi = 10.1016/j.biomaterials.2003.08.042 }} and neural tissue engineering{{cite journal | vauthors = Yang F, Xu CY, Kotaki M, Wang S, Ramakrishna S | title = Characterization of neural stem cells on electrospun poly(L-lactic acid) nanofibrous scaffold | journal = Journal of Biomaterials Science. Polymer Edition | volume = 15 | issue = 12 | pages = 1483–97 | date = 2004 | pmid = 15696794 | doi = 10.1163/1568562042459733 | s2cid = 2990409 }} as well.

File:Drug delivery diagram.png

Successful delivery of therapeutics to the intended target largely depends on the choice of the drug carrier. The criteria for an ideal drug carrier include maximum effect upon delivery of the drug to the target organ, evasion of the immune system of the body in the process of reaching the organ, retention of the therapeutic molecules from preparatory stages to the final delivery of the drug, and proper release of the drug for exertion of the intended therapeutic effect.{{cite journal| vauthors = Sharifi F, Sooriyarachchi AC, Altural H, Montazami R, Rylander MN, Hashemi N |title=Fiber based approaches as medicine delivery systems|journal=ACS Biomater Sci Eng|date=2016|volume=2|issue=9|pages=1411–1431|doi=10.1021/acsbiomaterials.6b00281|pmid=33440580|url=https://lib.dr.iastate.edu/me_pubs/316}} Nanofibers are under study as a possible drug carrier candidate.{{cite journal| vauthors = Ahn SY, Mun CH, Lee SH |title=Microfluidic spinning of fibrous alginate carrier having highly enhanced drug loading capability and delayed release profile|journal=RSC Adv|date=2015|volume=5|issue=20|pages=15172–15181|doi=10.1039/C4RA11438H|bibcode=2015RSCAd...515172A}}{{cite journal | vauthors = Garg T, Rath G, Goyal AK | title = Biomaterials-based nanofiber scaffold: targeted and controlled carrier for cell and drug delivery | journal = Journal of Drug Targeting | volume = 23 | issue = 3 | pages = 202–21 | date = April 2015 | pmid = 25539071 | doi = 10.3109/1061186X.2014.992899 | s2cid = 8398004 }}{{cite book| vauthors = Fogaça R, Ouimet MA, Catalani LH, Uhrich KE |title=Bioactive-based poly(anhydride-esters) and blends for controlled drug delivery|date=2013|publisher=American Chemical Society|isbn=9780841227996}} Natural polymers such as gelatin and alginate make for good fabrication biomaterials for carrier nanofibers because of their biocompatibility and biodegradability that result in no harm to the tissue of the host and no toxic accumulation in the human body, respectively. Due to their cylindrical morphology, nanofibers possess a high surface area-to-volume ratio. As a result, the fibers possess high drug-loading capacity and may release therapeutic molecules over a large surface area. Whereas surface area to volume ratio can only be controlled by adjusting the radius for spherical vesicles, nanofibers have more degrees of freedom in controlling the ratio by varying both the length and the cross-sectional radius. This adjustability is important for their application in drug delivery system in which the functional parameters need to be precisely controlled.

Preliminary studies indicate that antibiotics and anticancer drugs may be encapsulated in electrospun nanofibers by adding the drug into the polymer solution prior to electrospinning.{{cite journal | vauthors = Hu X, Liu S, Zhou G, Huang Y, Xie Z, Jing X | title = Electrospinning of polymeric nanofibers for drug delivery applications | journal = Journal of Controlled Release | volume = 185 | pages = 12–21 | date = July 2014 | pmid = 24768792 | doi = 10.1016/j.jconrel.2014.04.018 }}{{cite journal | vauthors = Yoo HS, Kim TG, Park TG | title = Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery | journal = Advanced Drug Delivery Reviews | volume = 61 | issue = 12 | pages = 1033–42 | date = October 2009 | pmid = 19643152 | doi = 10.1016/j.addr.2009.07.007 }} Surface-loaded nanofiber scaffolds are useful as adhesion barriers between internal organs and tissues post-surgery.{{cite journal | vauthors = Zong X, Li S, Chen E, Garlick B, Kim KS, Fang D, Chiu J, Zimmerman T, Brathwaite C, Hsiao BS, Chu B | display-authors = 6 | title = Prevention of postsurgery-induced abdominal adhesions by electrospun bioabsorbable nanofibrous poly(lactide-co-glycolide)-based membranes | journal = Annals of Surgery | volume = 240 | issue = 5 | pages = 910–5 | date = November 2004 | pmid = 15492575 | pmc = 1356499 | doi = 10.1097/01.sla.0000143302.48223.7e }}{{cite journal | vauthors = Kumbar SG, Nair LS, Bhattacharyya S, Laurencin CT | title = Polymeric nanofibers as novel carriers for the delivery of therapeutic molecules | journal = Journal of Nanoscience and Nanotechnology | volume = 6 | issue = 9–10 | pages = 2591–607 | date = 2006 | pmid = 17048469 | doi = 10.1166/jnn.2006.462 }} Adhesion occurs during the healing process and can bring on complications such as chronic pain and reoperation failure.{{cite journal | vauthors = Ignatova M, Rashkov I, Manolova N | title = Drug-loaded electrospun materials in wound-dressing applications and in local cancer treatment | journal = Expert Opinion on Drug Delivery | volume = 10 | issue = 4 | pages = 469–83 | date = April 2013 | pmid = 23289491 | doi = 10.1517/17425247.2013.758103 | s2cid = 24627745 }}

Although pathologic examination is the current standard method for molecular characterization in testing for the presence of biomarkers in tumors, these single-sample analyses fail to account for the diverse genomic nature of tumors.{{cite journal | vauthors = Chen JF, Zhu Y, Lu YT, Hodara E, Hou S, Agopian VG, Tomlinson JS, Posadas EM, Tseng HR | display-authors = 6 | title = Clinical Applications of NanoVelcro Rare-Cell Assays for Detection and Characterization of Circulating Tumor Cells | journal = Theranostics | volume = 6 | issue = 9 | pages = 1425–39 | date = 2016 | pmid = 27375790 | pmc = 4924510 | doi = 10.7150/thno.15359 }} Considering the invasive nature, psychological stress, and the financial burden resulting from repeated tumor biopsies in patients, biomarkers that could be judged through minimally invasive procedures, such as blood draws, constitute an opportunity for progression in precision medicine.

Liquid biopsy is an option that is becoming increasingly popular as an alternative to solid tumor biopsy.{{cite journal | vauthors = Ke Z, Lin M, Chen JF, Choi JS, Zhang Y, Fong A, Liang AJ, Chen SF, Li Q, Fang W, Zhang P, Garcia MA, Lee T, Song M, Lin HA, Zhao H, Luo SC, Hou S, Yu HH, Tseng HR | display-authors = 6 | title = Programming thermoresponsiveness of NanoVelcro substrates enables effective purification of circulating tumor cells in lung cancer patients | journal = ACS Nano | volume = 9 | issue = 1 | pages = 62–70 | date = January 2015 | pmid = 25495128 | pmc = 4310634 | doi = 10.1021/nn5056282 }} This is simply a blood draw that contains circulating tumor cells (CTCs) which are shed into the bloodstream from solid tumors. Patients with metastatic cancer are more likely to have detectable CTCs in the bloodstream but CTCs also exist in patients with localized diseases. It has been found that the number of CTCs present in the bloodstream of patients with metastatic prostate and colorectal cancer is prognostic of the overall survival of tumors.{{cite journal | vauthors = Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, Doyle GV, Matera J, Allard WJ, Miller MC, Fritsche HA, Hortobagyi GN, Terstappen LW | display-authors = 6 | title = Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer | journal = Journal of Clinical Oncology | volume = 23 | issue = 7 | pages = 1420–30 | date = March 2005 | pmid = 15735118 | doi = 10.1200/JCO.2005.08.140 | doi-access = free }}{{cite journal | vauthors = Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse M, Mitchell E, Miller MC, Doyle GV, Tissing H, Terstappen LW, Meropol NJ | display-authors = 6 | title = Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer | journal = Journal of Clinical Oncology | volume = 26 | issue = 19 | pages = 3213–21 | date = July 2008 | pmid = 18591556 | doi = 10.1200/JCO.2007.15.8923 | url = https://research.utwente.nl/en/publications/the-relationship-of-circulating-tumor-cells-to-tumor-response-progressionfree-survival-and-overall-survival-in-patients-with-metastatic-colorectal-cancer(45b03593-2227-4e98-8a44-ead38f8fa0b1).html }} CTCs also have been demonstrated to inform prognosis in earlier stages of the disease.{{cite journal | vauthors = Rack B, Schindlbeck C, Jückstock J, Andergassen U, Hepp P, Zwingers T, Friedl TW, Lorenz R, Tesch H, Fasching PA, Fehm T, Schneeweiss A, Lichtenegger W, Beckmann MW, Friese K, Pantel K, Janni W | display-authors = 6 | title = Circulating tumor cells predict survival in early average-to-high risk breast cancer patients | journal = Journal of the National Cancer Institute | volume = 106 | issue = 5 | pages = 1–11 | date = May 2014 | pmid = 24832787 | pmc = 4112925 | doi = 10.1093/jnci/dju066 }}

File:CTC mechanism.png

Recently, Ke et al. developed a NanoVelcro chip that captures the CTCs from the blood samples. When blood is passed through the chip, the nanofibers coated with protein antibodies bind to the proteins expressed on the surface of cancer cells and act like Velcro to trap CTCs for analysis. The NanoVelcro CTC assays underwent three generations of development. The first generation NanoVelcro Chip was created for CTC enumeration for cancer prognosis, staging, and dynamic monitoring.{{cite journal | vauthors = Lu YT, Zhao L, Shen Q, Garcia MA, Wu D, Hou S, Song M, Xu X, Ouyang WH, Ouyang WW, Lichterman J, Luo Z, Xuan X, Huang J, Chung LW, Rettig M, Tseng HR, Shao C, Posadas EM | display-authors = 6 | title = NanoVelcro Chip for CTC enumeration in prostate cancer patients | journal = Methods | volume = 64 | issue = 2 | pages = 144–52 | date = December 2013 | pmid = 23816790 | pmc = 3834112 | doi = 10.1016/j.ymeth.2013.06.019 }} The second generation NanoVelcro-LCM was developed for single-cell CTC isolation.{{cite journal | vauthors = Jiang R, Lu YT, Ho H, Li B, Chen JF, Lin M, Li F, Wu K, Wu H, Lichterman J, Wan H, Lu CL, OuYang W, Ni M, Wang L, Li G, Lee T, Zhang X, Yang J, Rettig M, Chung LW, Yang H, Li KC, Hou Y, Tseng HR, Hou S, Xu X, Wang J, Posadas EM | display-authors = 6 | title = A comparison of isolated circulating tumor cells and tissue biopsies using whole-genome sequencing in prostate cancer | journal = Oncotarget | volume = 6 | issue = 42 | pages = 44781–93 | date = December 2015 | pmid = 26575023 | pmc = 4792591 | doi = 10.18632/oncotarget.6330 }}{{cite journal | vauthors = Zhao L, Lu YT, Li F, Wu K, Hou S, Yu J, Shen Q, Wu D, Song M, OuYang WH, Luo Z, Lee T, Fang X, Shao C, Xu X, Garcia MA, Chung LW, Rettig M, Tseng HR, Posadas EM | display-authors = 6 | title = High-purity prostate circulating tumor cell isolation by a polymer nanofiber-embedded microchip for whole exome sequencing | journal = Advanced Materials | volume = 25 | issue = 21 | pages = 2897–902 | date = June 2013 | pmid = 23529932 | pmc = 3875622 | doi = 10.1002/adma.201205237 | bibcode = 2013AdM....25.2897Z }} The individually isolated CTCs can be subjected to single-CTC genotyping. The third generation Thermoresponsive Chip allowed for CTC purification.{{cite journal | vauthors = Hou S, Zhao H, Zhao L, Shen Q, Wei KS, Suh DY, Nakao A, Garcia MA, Song M, Lee T, Xiong B, Luo SC, Tseng HR, Yu HH | display-authors = 6 | title = Capture and stimulated release of circulating tumor cells on polymer-grafted silicon nanostructures | journal = Advanced Materials | volume = 25 | issue = 11 | pages = 1547–51 | date = March 2013 | pmid = 23255101 | pmc = 3786692 | doi = 10.1002/adma.201203185 | bibcode = 2013AdM....25.1547H }} The nanofiber polymer brushes undergo temperature-dependent conformational changes to capture and release CTCs.

Among many advanced electrochemical energy storage devices, rechargeable lithium-air batteries are of particular interest due to their considerable energy storing capacities and high power densities.{{cite journal| vauthors = Zhang B, Kang F, Tarascon JM, Kim JK |title=Recent advances in electrospun carbon nanofibers and their application in electrochemical energy storage|journal=Prog Mater Sci|date=2016|volume=76|pages=319–380|doi=10.1016/j.pmatsci.2015.08.002}}{{cite news|title=Lithium-air batteries: their time has come|url=https://www.economist.com/news/science-and-technology/21703358-new-type-electrical-cell-may-displace-lithium-ion-design-their-time-has|newspaper=The Economist|date=Aug 6, 2016}} As the battery is being used, lithium ions combine with oxygen from the air to form particles of lithium oxides, which attach to carbon fibers on the electrode. During recharging, the lithium oxides separate again into lithium and oxygen which is released back into the atmosphere. This conversion sequence is highly inefficient because there is significant voltage difference of more than 1.2 volts between the output voltage and the charging voltage of the battery meaning that approximately 30% of the electrical energy is lost as heat when the battery is charging. Also the large volume changes resulting from continuous conversion of oxygen between its gaseous and solid state puts stress on the electrode and limits its lifetime.

File:Li-air-solidstate.jpg

The performance of these batteries depends on the characteristics of the material that makes up the cathode. Carbon materials have been widely used as cathodes because of their excellent electrical conductivities, large surface areas, and chemical stability.{{cite journal| vauthors = Yang X, He P, Xia Y |title=Preparation of mesocellular carbon foam and its application for lithium/oxygen battery|journal=Electrochem Commun|date=2009|volume=11|issue=6|pages=1127–1130|doi=10.1016/j.elecom.2009.03.029}}{{cite journal| vauthors = Mitchell RR, Gallant BM, Thompson CV, Shao-Horn Y |title=All-carbon-nanofiber electrodes for high-energy rechargeable LiO2 batteries|journal=Energy Environ Sci|date=2011|volume=4|issue=8|pages=2952–2958|doi=10.1039/c1ee01496j|s2cid=96799565}} Especially relevant for lithium-air batteries, carbon materials act as substrates for supporting metal oxides. Binder-free electrospun carbon nanofibers are particularly good potential candidates to be used in electrodes in lithium-oxygen batteries because they have no binders, have open macroporous structures, have carbons that support and catalyze the oxygen reduction reactions, and have versatility.{{cite journal| vauthors = Singhal R, Kalra V |title=Binder-free hierarchically-porous carbon nanofibers decorated with cobalt nanoparticles as efficient cathodes for lithium-oxygen batteries|journal=RSC Adv|date=2016|volume=6|issue=105|pages=103072–103080|doi=10.1039/C6RA16874D|bibcode=2016RSCAd...6j3072S}}

Zhu et al. developed a novel cathode that can store lithium and oxygen in the electrode they named nanolithia which is a matrix of carbon nanofibers periodically embedded with cobalt oxide.{{cite journal| vauthors = Zhu Z, Kushima A, Yin Z, Qi L, Amine K, Lu J, Li J |title=Anion-redox nanolithia cathodes for Li-ion batteries|journal=Nature Energy|date=2016|volume=1|issue=8|pages=16111|doi=10.1038/nenergy.2016.111|bibcode=2016NatEn...116111Z|s2cid=366009}} These cobalt oxides provide stability to the normally unstable superoxide-containing nanolithia. In this design, oxygen is stored as LiO₂ and does not convert between gaseous and solid forms during charging and discharging. When the battery is discharging, lithium ions in nanolithia and react with superoxide oxygen the matrix to form Li₂O₂, and Li₂O. The oxygen remains in its solid state as it transitions among these forms. The chemical reactions of these transitions provide electrical energy. During charging, the transitions occur in reverse.

Polymer optical fibers have generated increasing interest in recent years.{{cite journal| vauthors = Wang X, Drew C, Lee SH, Senecal KJ, Kumar J, Samuelson LA |title=Electrospun nanofibrous membranes for highly sensitive optical sensors|journal=Nano Lett|date=2002|volume=2|issue=11|pages=1273–1275|doi=10.1021/nl020216u|citeseerx=10.1.1.459.8052|bibcode=2002NanoL...2.1273W}}{{cite journal| vauthors = Yang Q, Jiang X, Gu F, Ma Z, Zhang J, Tong L |title=Polymer micro or nanofibers for optical device applications|journal=J Appl Polym Sci|date=2008|volume=110|issue=2|pages=1080–1084|doi=10.1002/app.28716}} Because of low cost, ease of handling, long wavelength transparency, great flexibility, and biocompatibility, polymer optical fibers show great potential for short-distance networking, optical sensing and power delivery.{{cite journal| vauthors = Zubia J, Arrue J |title=Plastic optical fibers: an introduction to their technological processes and applications|journal= Optical Fiber Technology|date=2001|volume=7|issue=2|pages=101–140|doi=10.1006/ofte.2000.0355|bibcode=2001OptFT...7..101Z}}{{cite journal| vauthors = Peters K |title=Polymer optical fiber sensors—a review|journal=Smart Mater Struct|date=2011|volume=20|issue=1|pages=013002|doi=10.1088/0964-1726/20/1/013002|bibcode=2011SMaS...20a3002P|s2cid=52238312}}

Electrospun nanofibers are particularly well-suitable for optical sensors because sensor sensitivity increases with increasing surface area per unit mass. Optical sensing works by detecting ions and molecules of interest via fluorescence quenching mechanism. Wang et al. successfully developed nanofibrous thin film optical sensors for metal ion (Fe³⁺ and Hg²⁺) and 2,4-dinitrotoluene (DNT) detection using the electrospinning technique.

Quantum dots show useful optical and electrical properties, including high optical gain and photochemical stability. A variety of quantum dots have been successfully incorporated into polymer nanofibers.{{cite journal | vauthors = Liu H, Edel JB, Bellan LM, Craighead HG | title = Electrospun polymer nanofibers as subwavelength optical waveguides incorporating quantum dots | journal = Small | volume = 2 | issue = 4 | pages = 495–9 | date = April 2006 | pmid = 17193073 | doi = 10.1002/smll.200500432 }} Meng et al. showed that quantum dot-doped polymer nanofiber sensor for humidity detection shows fast response, high sensitivity, and long-term stability while requiring low power consumption.{{cite journal | vauthors = Meng C, Xiao Y, Wang P, Zhang L, Liu Y, Tong L | title = Quantum-dot-doped polymer nanofibers for optical sensing | journal = Advanced Materials | volume = 23 | issue = 33 | pages = 3770–4 | date = September 2011 | pmid = 21766349 | doi = 10.1002/adma.201101392 | s2cid = 6264401 }}

Kelly et al. developed a sensor that warns first responders when the carbon filters in their respirators have become saturated with toxic fume particles.{{cite journal | vauthors = Kelly TL, Gao T, Sailor MJ | title = Carbon and carbon/silicon composites templated in rugate filters for the adsorption and detection of organic vapors | journal = Advanced Materials | volume = 23 | issue = 15 | pages = 1776–81 | date = April 2011 | pmid = 21374740 | doi = 10.1002/adma.201190052 | doi-access = free }} The respirators typically contain activated charcoal that traps airborne toxins. As the filters become saturated, chemicals begin to pass through and render the respirators useless. In order to easily determine when the filter is spent, Kelly and his team developed a mask equipped with a sensor composed of carbon nanofibers assembled into repeating structures called photonic crystals that reflect specific wavelengths of light. The sensors exhibit an iridescent color that changes when the fibers absorb toxins.

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Electrospun nanofibers are useful for removing volatile organic compounds (VOC) from the atmosphere. Scholten et al. showed that adsorption and desorption of VOC by electrospun nanofibrous membrane were faster than the rates of conventional activated carbon.{{cite journal | vauthors = Scholten E, Bromberg L, Rutledge GC, Hatton TA | title = Electrospun polyurethane fibers for absorption of volatile organic compounds from air | journal = ACS Applied Materials & Interfaces | volume = 3 | issue = 10 | pages = 3902–9 | date = October 2011 | pmid = 21888418 | doi = 10.1021/am200748y | hdl-access = free | hdl = 1721.1/81271 | s2cid = 7486858 }}

Airborne contamination in the personnel cabins of mining equipment is of concern to the mining workers, mining companies, and government agencies such as the Mine Safety and Health Administration (MSHA). Recent work with mining equipment manufacturers and the MSHA has shown that nanofiber filter media can reduce cabin dust concentration to a greater extent compared to standard cellulose filter media.{{cite journal| vauthors = Graham K, Ouyang M, Raether T, Grafe T, McDonald B, Knauf P |title=Polymeric nanofibers in air filtration applications|journal=Fifteenth Annual Technical Conference & Expo of the American Filtration & Separations Society|date=2002}}

Nanofibers can be used in masks to protect people from viruses, bacteria, smog, dust, allergens and other particles. Filtration efficiency is at about 99.9% and the principle of filtration is mechanical. Particles in the air are bigger than pores in nanofiber web, but oxygen particles are small enough to pass through.

Nanofibers have the capabilities in oil–water separation, most particularly in sorption process when the material in use has the oleophilic and hydrophobic surfaces. These characteristic enable the nanofibers to be used as a tool to combat either oily waste- water from domestic household and industrial activities, or oily seawater due to the oil run down to the ocean from oil transportation activities and oil tank cleaning on a vessel.

Sportswear textile with nanofiber membrane inside is based on the modern nanofiber technology where the core of the membrane consists of fibers with a diameter 1000× thinner than human hair. This extremely dense "sieve" with more than 2,5 billion of pores per square centimeter works much more efficiently with vapor removal and brings better level of water resistance. In the language of numbers, the nanofiber textile brings the following parameters:

·       RET 1.0 vapor permeability and 10,000 mm water column (version preferring breathability)

·       RET 4.8 vapor permeability and 30,000 mm water column (version preferring water resistance)

Nanofiber apparel and shoe membranes consist of polyurethane so its production is not harmful to nature. Membranes to sportswear made from nanofiber are recyclable.

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• Subwavelength-diameter optical fiber
• Nanofiber seeding
• Polyaniline nanofibers

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Category:Fibers

Category:Nanoparticles by morphology