**2. Nanofiber production methods**

Nanofiber production techniques can be divided into two main class: top-down and bottom-up approaches. Chemical and mechanical methods are considered in top-down approaches. In top-down techniques, nanofibers are formed from bulk materials. On the other hand, in bottom-up approaches such as electrospinning, drawing, phase separation, etc., nanofiber formation occurs from composing molecules. This chapter mainly focuses on bottom-up approaches since they are the widely used class of nanofiber production methods.

#### **2.1 Electrospinning**

Electrospinning (ES) directly emerged from electrospraying (Electrohydrodynamic spray (EHD)), which was discovered by Morton and Cooley in 1902. Both methods depend on dispersing fluids by using electrostatic forces. There is one important distinction between these methods. By using ES, continuous fibers can be produced, whereas only small droplets are formed in EHD. After the electrospinning method was found to be more suitable for producing nanofibers rather than EHD, this method received more attention, and more studies were carried out in this field. As a result of these studies over the years, electrospinning method has undergone many modifications. By using different types of ES, one can produce hollow fibers, core-shell fibers, nanoparticles, or drug-incorporated fibers, etc.

#### *2.1.1 Traditional electrospinning*

For traditional ES, three main components are needed: (i) a high voltage source, (ii) syringe pump (nozzle), and (iii) a grounded collector (**Figure 1a**). The nozzle is preferably a metallic needle with a blunt tip to proper observation of the Taylor cone. During the ES process, first certain amount of polymeric solution (preferably dissolved in a volatile solvent with a w:v ratio.) is placed into a proper syringe and then to the syringe pump. Then high voltage is applied to the tip of the nozzle, and the elongating conical shape of the droplet is observed. To form nanofibers, the electrostatic force has to overcome the surface tension of the droplet, then Taylor Cone occurs at the tip of the nozzle, and a charged jet ejects from the Taylor Cone, resulting in the formation of nanofibers following by the fast evaporation of the solvent [10].

*Nanofibers: Production, Characterization, and Tissue Engineering Applications DOI: http://dx.doi.org/10.5772/intechopen.102787*

#### **Figure 1.**

*(a) Traditional electrospinning setup, (b) multijet electrospinning setup, and (c) coaxial electrospinning setup. (a and c were reproduced with the permission from Gonçalves et al. [7], Ura et al. [8], and b was reproduced with the permission from Wu et al. [9]).*

Morphology of the formed fibers can be controlled by many factors such as flow rate of the syringe pump, concentration of the polymer solution, collector type, solution viscosity, applied voltage, distance between the collector and the nozzle, diameter of the nozzle, etc. And each of these factors affects the fiber morphology significantly. For example, by increasing the voltage, fiber diameter can be decreased, low polymer concentrations can cause electrospraying rather than electrospinning, or increasing the flow rate can reduce the fiber diameter [11]. So, all these parameters have to be optimized before the ES process began in order to obtain fibers with maximum performance.

#### *2.1.2 Multijet electrospinning*

This method is also called "Multi Needle ES" in the literature. The reason for its development is to improve the productivity and produce composite fibers that cannot be dissolved in regular solvents (**Figure 1b**).

Needle diameter, needle number, and configuration play an important role in this approach such as the other ES methods. Unfortunately, this method holds one major drawback, which is a strong repulsion among the jets because of the multi needle system. This repulsion, which is generated by the coulomb force, may cause reduced fiber deposition and poor fiber quality. To avoid this problem, needles must be oriented at appropriate distance [12].

#### *2.1.3 Coaxial electrospinning*

Coaxial ES method is used to form core-shell nanofibers by using multiple syringe pumps or one syringe pump with multiple feeding systems. Mainly, a polymer and a composite solution, one is to form shell and the other is to form core parts, can be used individually, or two different polymer solutions can be employed as forerunner solutions (**Figure 1c**). Directed by the electrostatic repulsions between the surface charges, the polymer solution, which will form the shell part

of the composite nanofibers, will be lengthened and will create viscous stress. After that this stress will be delivered to the core layer, and the polymer solution, which will form the core part, will be promptly stretched. As a result, composite jets will be formed, which will have coaxial structures [13].

#### *2.1.4 Melt electrospinning*

Addition to the conventional ES setup, melt ES technique requires a heating device such as heat guns, lasers, or electrical heating devices (**Figure 2a**). Polymer solution must stay in its molten state by a constant heat source. Main difference between melt ES and conventional ES method is the fiber formation process. In melt ES, instead of a solution, a molten polymer is used, and desired product is obtained on cooling; however, in conventional ES, fibers are formed with the help of solvent evaporation [14]. Other than this difference, the parameters that affect the fiber diameter, fiber quality, and the ES process are the same with the conventional ES method.

Main advantages of this method can be described as the absence of a solvent system and the high throughput rate of the polymer. This method can be used with the polymers that do not have a suitable solvent at room temperature. But in most of the cases, one of the major problems of melt ES is broad fiber diameter range due to the high viscosity of the melt polymer. Because of the high viscosity of the polymer, greater charge is required to initiate the jets. To reduce the fiber diameter or to obtain fibers with uniform diameters, some research groups used polymer blends or additives [17]. Requirement of high temperatures to melt the polymer can also be a disadvantage at this point. The melting temperature of the polymer can affect the structure and function of these additives (e.g., proteins, drugs, etc.) [18]. This situation makes selection and optimization steps critical.

#### *2.1.5 Centrifugal electrospinning*

Centrifugal ES is known by force spinning or rotary spinning as well. In this method, the electric field is replaced with a centrifugal force, which distinguishes centrifugal ES from conventional ES. Fiber formation is almost the same with conventional ES with a slight difference, instead of electric field, rotating speed surpasses the critical point to form a Taylor cone, and then the liquid jet gets ejected from the needle (**Figure 2b**) [19]. Therefore, rotating speed is one of the key parameters that determines the quality of the fibers along with the nozzle configuration, collector type, temperature, etc.

#### **Figure 2.**

*(a) Melt electrospinning setup, (b) centrifugal electrospinning setup, and (c) magnetic-field-assisted electrospinning setup. (a was reproduced with the permission from Brown et al. [14]; b was reproduced with the permission from Taghavi et al. [15]; and c was reproduced with the permission from Blachowicz and Ehrmann [16]).*

*Nanofibers: Production, Characterization, and Tissue Engineering Applications DOI: http://dx.doi.org/10.5772/intechopen.102787*

There are many advantages of this system due to the use of centrifugal force in place of electric field. Numerous conductive and nonconductive polymers can be electrospun with this method. Because no high voltage is needed, this method lightens safety-related concerns greatly. By adjusting the rotating speed, production efficiency can be improved, and large-scale production is allowed as well. Main limitations of conventional ES process (high voltage, misdirection of the jet, high cost, etc.) can be eliminated with this method. Aside of the advantages, the main disadvantage of this method is the spinneret design and material properties, which can highly affect the fiber quality and the yield of the process [20].

#### *2.1.6 Magnetic-field-assisted electrospinning*

In this method, magnetic properties are gained by incorporating magnetic nanoparticles to the polymer solution or using polymers that can respond to magnetic field (**Figure 2c**). This magnetic field can be obtained by two parallel permanent magnets, Helmholtz coils, or a magnetic field responder solution [21]. Besides mixing different polymers, adding non-polymeric materials (e.g., metals, ceramics, etc.) is another approach by which magnetic-field-assisted ES can be used. Fibers that are maintained with this method are reported to be more uniform. By using magnetic field fiber splitting from the jet can be prevented because of the magnetic field orientation. High velocity of the process supports smaller fiber diameter [22].

#### *2.1.7 Needleless electrospinning*

Some researchers proposed a new technique called "Needleless ES" to avoid the limitation caused by the capillaries and needles. Basis of this approach relies on a single principle, which is: Waves of an electrically conductive liquid self-organize on a mesoscopic scale and form jets when the intensity of the applied electrical field rises above a critical value (**Figure 3a**). Setup of the system can be divided in two groups: one of which is ES with a constrained feeding system and ES with an unconstrained feeding system. For the first system, a supply for the polymer solution, which is afterward injected into a closed nozzle, is preferred. On the contrary, for the second system, no nozzles are needed because the Taylor cones are formed on a free liquid surface. For both groups, high voltage source is a must to attract the polymer jets into nanofibers [25].

With the use of multiple jets without the needles, chances to increase the production rate of nanofibers are higher compared with the traditional ES systems. Some studies report an increase in polymer yield compared with single-needle

#### **Figure 3.**

*(a) Needleless electrospinning setup, (b) emulsion electrospinning setup. (a was reproduced with the permission from Li et al. [23], and b was reproduced with the permission from Nikmaram et al. [24]).*

solution and an improvement in fiber deposition, in opposition to multi-needle ES, which resulted from a reduction in mutual fiber repulsion [26].

## *2.1.8 Emulsion electrospinning*

Emulsion ES is developed to produce fibers from two immiscible solutions. To blend these immiscible solutions and obtain an emulsion, vigorous stirring is required. Then this emulsion is loaded a glass syringe connected to a needle and a high voltage source (**Figure 3b**). Because this emulsion contains two immiscible solutions, fibers are difficult to produce due to properties and immiscible phases of these solutions. To overcome these difficulties, nanoparticles and surfactants such as detergents, sodium dodecyl sulfate, etc., are generally used. Even with this solution, there is a constant necessity for the emulsion to stay stable through the ES process, which is a major drawback [27, 28].

### **2.2 Wet spinning**

Wet spinning (WS) is an alternative nanofiber fabrication method for polymers that are derived from natural sources. It is much cheaper and simpler in comparison to any ES method. Because there is no high voltage source, it is much easier to load therapeutic agents into fibers, which expands the range of polymers from natural or synthetic sources handled by means of WS [29]. It is also a developing approach, but it is possible to gather wet-spun nanofibers to produce biodegradable and biocompatible scaffolds with a 3D network for regenerative medicine approaches. This method is mainly based on extrusion of a polymeric solution into a coagulation bath where the solution in the coagulation bath contains a poor solvent or solvent/ non-solvent mixture (**Figure 4**).

Main goal here is to obtain coagulating fibers in the coagulation bath, which at the end solidifies as a constant fiber, as the extrusion process continues. Typical WS setup composed of a needle contains the polymeric solution, which is placed in a syringe pump and a coagulation medium. The needle must be immersed in the medium to initiate fiber coagulation. Different strategies have been developed for the collection or assembly of the fibers such as rotating drum, 3D assembly of the fibers by thermomechanical treatments, manually or computer-controlled motion of the coagulation bath or the needle, etc. After the WS setup is complete, quality and final morphology of the fibers still depend on several parameters, which include temperature, solvent system, properties of the selected polymer, needle diameter, flow rate of the syringe pump [31].

**Figure 4.** *Wet spinning setup. (Figure was reproduced and adapted with the permission from Wang et al. [30]).*

*Nanofibers: Production, Characterization, and Tissue Engineering Applications DOI: http://dx.doi.org/10.5772/intechopen.102787*

#### **2.3 Drawing**

Drawing technique is usually used to produce continuous individual nanofibers. It is based on a sharp probe tip or a micropipette, which is soaked into the edge of the droplet deposited on a container. Then the sharp tip is withdrawn from the solution with a constant rate (usually 100 μm/s) to fabricate liquid fibers. The drawn nanofibers will be deposited on the surface by contacting the surface with the edge of the micropipette (**Figure 5a**). To form a 3D structure or a network, this process was repeated several times for every droplet [33], and continuous fibers in many adjustments can be fabricated with drawing method to use in biomedical applications.

In addition, specific control of the drawing process parameters such as drawing speed, viscosity, properties of the used polymer allows repeatability of the process, control of the fiber quality and fiber dimensions. Besides the advantages such as fabricating continuous fibers, simplicity, and the cost-effectiveness of the process, there are also some limitations. Because drawing causes nanofibers to be produced one single fiber at a time, productivity of this process is low. The only material type that can be used in this process is viscoelastic materials. Viscoelastic materials can resist the increased stress produced by drawing, and they can preserve their integration while going through a strong deformation [34].

## **2.4 Template synthesis**

Template synthesis method allows to produce solid or hollow, discontinuous nanofibers with different properties such as polymeric, metallic, ceramic, semiconductor nanofibers. It is possible to convert multiple materials into fibrils or tubules in nanoscale diameter to use them in many applications, which include regenerative medicine, electronics, optoelectronics, gas sensors, etc. [35].

This method relies on the usage of a nanoporous membrane as a template/ mold, containing cylindrical pores. The template/mold often refers to a metal oxide membrane such as aluminum oxide membranes or silica-based membranes, etc. Nanofibers are formed by passing through the polymer solution from the pores of the nanoporous membrane/template (**Figure 5b**). During the extrusion, polymer

#### **Figure 5.**

*(a) Drawing method, (b) template synthesis method, and (c) phase separation method. (Figures were adapted from Ramakrishna et al. [32]).*

solution comes in contact with the solidifying solution and nanofibers are formed. The major disadvantage of this method is the continuity of the fibers. Only a few micrometers long fibers can be obtained with this method, and the diameter of these fibers depends on the pore size of the template [36]. By using template with different pore sizes, a variety of diameters can be achieved with template synthesis.

## **2.5 Phase separation**

Phase separation method was developed by Zhang and Ma to mimic the 3D structure of collagen under the name of thermally induced liquid-liquid phase separation (**Figure 5c**). This method is mainly composed of five stages, which include preparing a homogeneous polymer solution, phase separation process, gelation, extraction of the solvent, freezing, and freeze-drying under the vacuum. Polymer solution is often prepared by dissolving the polymer at room temperature. Then the solution reaches the gelation temperature, which is the most critical step in this method because the duration of gelation depends on the concentration of the polymer and the gelation temperature. If the polymer acquires high gelation temperature, platelet-like structures are formed due to the nucleation of crystals so low gelation temperatures are required for this process. After gelation step was completed, solvent was extracted from the gel with water, and the freeze-drying stage was applied to the final product [37, 38].

For this method, minimum equipment is needed. Nanofiber matrix can be directly fabricated, and by adjusting the polymer concentration, properties of the matrix can be accustomed. Process parameters such as polymer concentration, polymer type, solvent type, etc., were found to influence the nanofiber quality, morphology, and the final nanofibrous matrix. The matrix fabricated by the phase separation method exhibits high porosity of almost 98% within the overall material. The major drawback of this method is that only a few polymers (e.g., polylactide, polyglycolide, etc.) can be used to obtain nanofibers by phase separation due to the fact that not all polymers are compatible with this process since it requires a certain gelation capability [39].

#### **2.6 Self-assembly**

This method relies on the idea of spontaneous organization of amphiphile compounds, which can be considered as active molecules (**Figure 6**). Because self-assembly is a bottom-up fabrication method, it is based on gathering small units

**Figure 6.** *Self-assembly method. (Figure was adapted from Xu et al. [40]).*

#### *Nanofibers: Production, Characterization, and Tissue Engineering Applications DOI: http://dx.doi.org/10.5772/intechopen.102787*

together by the help of intermolecular forces such as hydrogen bonding, hydrophobic interactions, electrostatic reactions, biomolecule-specific interactions, etc. These units will organize and arrange themselves to form macromolecular nanofibers.

The overall shape of the nanofibers is determined by the shape of small units. With this method, it is possible to produce nanofibers smaller than 100 nm with a length of several micrometers, but the process is time-consuming. Also, low productivity, difficult control of the fiber dimensions, and limited active compound choices, which can self-assemble themselves, are the main disadvantages of self-assembly method [41].

## **2.7 Interfacial polymerization**

This method depends on two different monomers, which can dissolve in different phases. Basically, this is a polycondensation reaction between two reactive monomers, which are dissolved in immiscible solvents. After these two different phases are prepared and mixed, polymerization will occur at the interface of the emulsion droplet. Homogeneous nucleated growth is the key factor in interfacial polymerization [42]. By separating the monomer precursors in different phases, localized reaction and nanofiber formation can be achieved (**Figure 7**).

By selecting different kinds of monomers, a variety of polymers can be synthesized. The properties and quality of the nanofibers are highly dependent on the reactivity and concentration of the monomers, reactive groups attached to the monomers, and the stability of the interface [44].

#### **Figure 7.**

*Snapshots showing interfacial polymerization of aniline in a water/chloroform system. From a to e, the reaction times are 0, 1.5, 2.5, 4, and 10 min, respectively. (Figure was reproduced and adapted with the permission from Huang et al. [43]).*
