A Review on the Electrospinning of Polymer Nanofibers and Its Biomedical Applications

: Polymeric nanofibers have emerged as a captivating medium for crafting structures with biomedical applications. Spinning methods have garnered substantial attention in the context of medical applications and neural tissue engineering, ultimately leading to the production of polymer fibers. In comparison with polymer microfibers, polymer nanofibers boasting nanometer-scale diameters offer significantly larger surface areas, facilitating enhanced surface functionalization. Consequently, polymer nanofiber mats are presently undergoing rigorous evaluation for a myriad of applications, including filters, scaffolds for tissue engineering, protective equipment, reinforcement in composite materials, and sensors. This review offers an exhaustive overview of the latest advancements in polymer nanofiber processing and characterization. Additionally, it engages in a discourse regarding research challenges, forthcoming developments in polymer nanofiber production, and diverse polymer types and its applications. Electrospinning has been used to convert a broad range of polymers into nanoparticle nanofibers, and it may be the only approach with significant potential for industrial manufacturing. The basics of these spinning techniques, highlighting the biomedical uses as well as nanostructured fibers for drug delivery, disease modeling, regenerative medicine, tissue engineering, and bio-sensing have been explored.


Introduction
Nanotechnology has become a ubiquitous force, impacting a diverse array of fields worldwide, including electronics, medical treatments, industry, military systems, construction materials, and environmental remediation, such as water treatment and air purification [1].Central to this domain is the manipulation and utilization of materials and structures at molecular, polymer, and nanostructure levels, harnessing distinct properties and phenomena of matter within the 1 to 100 nm size range.Over the past decade, polymer nanofibers, a pivotal class of nanomaterials, have emerged as a focal point of exploration.These nanofibers are defined as fibers with diameters on the order of 100 nm and find application in nanotechnology and nanostructured materials [2].Notably, sub-micrometer fibers, measuring less than 100 nm in dimension and fabricated with advanced techniques like electrospinning, have also gained prominence. Due to their nanoporosity distribution, high surface area-to-volume ratio, low weight, and customizable surface properties, nanofibers are exceptionally suited for applications such as water and air filtration, membranes, protective clothing, and drug delivery systems [3].Moreover, nanofibers offer avenues for precise surface modification, enhancing characteristics like water solubility, biocompatibility, and bio-recognition.These attributes position polymer nanofibers at the forefront of healthcare and biotechnology applications [4].
From a biological standpoint, a multitude of natural biomaterials exist in fibrous configurations, including silk, collagen, keratin, and various polysaccharides.These biomaterials display fibrous structures organized hierarchically, extending down to the nanoscale, providing valuable information for biomimicry approaches.Consequently, polymer nanofibers offer a means to emulate and replicate these intricate biosystems [5].Notably, the research underscores the profound influence of nanoscale surface characteristics and topography, in conjunction with surface chemistry, on cellular behavior, impacting cell attachment, alignment, activation, orientation, and proliferation [6,7].Cell responses, such as alignment with 66 nm collagen fiber banding, further emphasize the remarkable sensitivity of cells to nanoscale cues, even down to dimensions as small as 5 nm, revealing cellular interactions at scales significantly smaller than the cells themselves [8].
Polymer nanofiber processing variables and material structures play crucial roles in the relationship between the structure and characteristics of polymer nanofibers.Surface area, mechanical strength, and porosity undergo significant influence from the nanofiber's diameter, determined by the electrospinning voltage and solution viscosity.Smaller diameters yield larger surface areas and enhanced mechanical performance.The alignment and positioning of nanofibers are affected by electrospinning conditions like temperature and humidity, contributing to improved mechanical traits in well-aligned nanofibers [9].Material properties such as biocompatibility, chemical reactivity, and thermal stability are determined by the structure of a material, which is governed by the choice of solvent and polymer.The unique features of various polymers make them suitable for a range of applications.In addition, depending on the requirements of the application, post-processing procedures like cross-linking and functionalization can further customize the structure to improve stability and provide certain functions.For polymer nanofibers to reach their full potential in diverse technical sectors, it is essential to comprehend and optimize a few of their properties [8][9][10].
This review aims to comprehensively survey contemporary applications of polymer nanofibers in the biomedical and biotechnological domains.Notable applications encompass tissue engineering, controlled drug delivery, wound-healing dressings, molecular separation, biosensors, medical implants, dental nanocomposites, and the storage of bioactive agents [9][10][11].A spectrum of manufacturing techniques, including self-assembly, template synthesis, electrospinning, melt-blown, and phase separation, contribute to the production of polymer nanofibers suitable for diverse applications [10].Among these, electrospinning stands out as a cost-effective and versatile method, uniquely capable of producing continuous nanofibers on an industrial scale [11].Electrospinning, a well-established electrostatic spinning process, generates ultrafine nanofibers to fibers with diameters ranging from 10 nm to microns, thereby facilitating diverse applications [12].
Two primary approaches, top-down and bottom-up, shape nanofiber synthesis.Topdown methodologies transform bulk materials into nanofibers using physical, biological, or chemical treatments.In contrast, bottom-up strategies rely on molecular assembly, incorporating techniques like phase separation, electrochemical assembly, and interfacing polymerization [13,14].This review not only explores various nanofiber synthesis techniques but also delves into their specific properties, catering to clinical needs like drug delivery, disease modeling, regenerative medicine, tissue engineering, and biosensing [15].Additionally, it examines prevailing constraints and perspectives, anticipating their influence on future biological applications.

Methods for the Fabrication of Polymer Nanofiber Synthesis and Constructing Materials
Studying fabrication methods is an important issue for nanofibers, and it has piqued the interest of academics as well as the industry.Several production procedures have been introduced to manufacture suitable nanofibers for diverse applications, including electrospinning (random, aligned, and core-shell nanofibers), drawing, self-assembly, and template synthesis [13][14][15].Electrospinning is simple, inexpensive, and capable of pro-ducing continuous nanofibers of diverse materials ranging from polymers to ceramics.Furthermore, electrospinning looks to be a one-of-a-kind method [13].Many techniques have been utilized for nanofibers; these techniques may be divided into two groups based on how the nanofibers are produced, namely, electrospinning techniques and chemical synthesis techniques [16].The use of electrostatic force to form fibers and non-electrospinning techniques that utilize mechanical force include drawing, template synthesis, etc.When deciding between these approaches, it is necessary to consider the desired alignment, cost, quantity, and amount of fibrous material required [17].

Template Synthesis
Polymeric, metallic, semiconductor, or ceramic nanofibers can be generated using the template synthesis process, which uses chemical or electrochemical oxidative polymerization over a porous membrane [18].In this technique, nanofibers are created by passing a polymer solution through nanoscale holes while providing one side with water pressure, resulting in polymer fiber creation upon contact with a solidifying solution.The template synthesis technique generates nanofibers and hollow nanofibers.Nanofibers and fibrils can be made in a microporous membrane or any fibrous pores [19].Pre-configuration is used to obtain the desired nanofiber shape.It depicts a process for creating nanofiber self-assembly, phase separation, and electron spinning to make sol-gel nanofibers [20].At the nanoscale, nanofibers are derived using template synthesis.Electrode positions are used to fill cylindrical pores.Below the template, nanofibers are generated.One of the benefits of this technology is the ability to create nanofibers with varying diameters by utilizing multiple templates [21].

Phase Separation
The phase separation technique separates polymers using physical mismatch.The solvent phase is removed from the solution, leaving the other phase behind.
The following are the four basic phases of this method: • At a normal temperature or at a higher temperature, polymer dissolution in a solvent occurs.• The most challenging phase in controlling nanofiber shape is gelation (porosity).The gelation time varies depending on the polymer content and the gelation temperature.

•
Using water to extract the solvent from the gel.• The last step is vacuum freezing and freeze-drying.
The qualities of nanofiber are affected by the concentration; as the polymer concentration rises, the fiber porosity decreases, and the properties of the fibers improve [22].The initial step in this process is to create a homogeneous solution by dissolving the polymer at higher to lower temperatures (25 • C), followed by extracting the gel by maintaining temperature.Then, nanofibrous matrices form due to phase separation, and finally, the matrix is separated, which results in the formation of nanofibers [23].In this process, the requirements for the bare minimum equipment and matrix are directly produced, with the mechanical characteristics of the matrix being adjusted by varying the polymer concentration.The phase separation process has only been used to make nanofibers from a few polymers, such as polylactide (PLA) and polyglycolide [24].This process is not useful for long continuous fibers, and, as above mentioned, this process requires phase separation, so it is not useful for all types of polymers, which restricts the usage of this technology.

Drawing
Drawing is a simple process for producing fibers.The fact that this procedure simply requires a micropipette or sharp tip is considered its greatest benefit.A sharp tip is used in this procedure to pull a droplet of an initially placed polymer as liquid fibers [25].The liquid is then evaporated, owing to the increased surface area, causing the liquid fibers to solidify.To prevent the volume shrinkage problem that restricts the continuous drawing of the fibers and affects their diameter, hollow glass micropipettes can be used instead of the sharp tip with a constant dose of the polymer [26].The micropipette is slowly extracted from the liquid at a low speed (compared with other processes) after being dipped into the droplet using a micromanipulator; as a fine result, nanofibers are pulled and placed on the surface by contacting the end of the micropipette.To make a nanofiber, this technique is performed numerous times on each droplet [27].This approach may be used to create continuous nanofibers in any configuration [16].In addition, accurate control of important drawing parameters such as speed and viscosity may be obtained, allowing for reproducibility and control of the produced fabricated fiber dimensions.This procedure can only be utilized with viscoelastic materials, which is a limitation that leads to the use of other methods [28].

Self-Assembly
In the self-assembly process, molecules and atoms sort out and assemble themselves using weak and non-covalent forces, electrostatic interactions, and hydrogen bonding to form a stable structure [29].The self-assembly approach may be used to create a variety of structures, including unilamellar and multilamellar vesicles, bilayers, nanoparticles, membranes, fibers, films, micelles, tubes, and capsules [30].Self-assembly is also used to create peptide and peptide amphiphile nanofibers.An amphiphilic peptide was devised based on the self-assembly technique to facilitate the synthesis of a thermally stable protein.A fiber obtained using the self-assembly technique can be much thinner than that obtained using electrospinning; however, the procedure's difficulty and low productivity are the main issues with the self-assembly approach [31,32].Self-assembly peptides can provide scaffolds that increase the luminescence efficiency of nanoclusters.Natural structural materials self-assemble as they acquire the desired qualities such as tensile strength, thermal stability, and biocompatibility [32].

Electrospinning
Spinning methods entail mechanical drawing and solidification, resulting in fibers [33].Fiber-based materials with varying morphology structure and qualities may be produced using the spinning method, material selection, and processing factors (Figure 1).The most commonly used spinning technologies are electrospinning, microfluidic spinning, centrifugal spinning, and solution blow spinning.All these spinning techniques are dependent on the polymer concentration, voltage, type of solvent, distance between electrodes, temperature, and other factors [34] (Figure 2).Various spinning processes are used to develop nanofibers from a diverse variety of artificial and natural polymers, and also from mixtures [35].After deep analysis and investigation, the impact of these variables on the quality, shape, and ultimate diameter of nanofibers proved that all these factors are important for biomedical applications (Table 1).Kong and Ziegler [36] created nanofibers for a range of further applications.
In summary, spinning is the initial phase where the polymer solution is extruded and electrostatic forces are used to form the nanofibers, while drawing refers to the subsequent/*manipulation or elongation of these fibers to achieve specific characteristics in the produced nanofibrous materials.Both spinning and drawing methods are crucial in the electrospinning process for creating nanofibers with tailored properties suitable for various applications.
The following are important aspects of electrospinning: • A proper solvent for dissolving the polymer should be provided.
• The vapor pressure of the solvent needs to be high enough for the fiber to maintain its integrity when it reaches the target but not too high that it hardens before it reaches the nanoscale range.• The solvent surface tension and viscosity must be neither too high, to prevent the formation of a jet, nor too low, to enable the solution to drain easily from the pipette.• The power source should be sufficient to overcome the viscosity and surface tension of the polymer solution and sustain the jet from the pipette.

•
Maintaining the distance between the pipette and the surface to avoid sparks between the electrodes allows for the evaporation of the solvent to produce fibers.The most promising for a high production rate, low cost, and high production safety The main issue with centrifugal spinning is material qualities [45][46][47][48] Drum and mandrel spinning

Extracellular matrix formation of the wound in animal models
Well-aligned polymer Poor mechanical motion [49,50] The most popular fiber-forming technology is electrospinning, which uses electrostatic forces to generate polymer nanofibers [46].A high voltage is applied to a polymer solution in a syringe.A counter electrode is a plate coated with a sheet of aluminum positioned at a distance of a few cm [47].Similar charges concentrate in the polymer solution when an electric field is applied, resulting in a strong repulsive force strong enough to overcome the surface tension and viscous drag force of the polymer solution [48] (Figure 1).As a result, a stream of fluid freely emerges from the needle, subdividing into millions of nanoto submicron-sized jets that deposit as nanofibers on the counter electrode or aluminum foil.This sheet is made up of randomly arranged fibers, with the thickness increasing as the electrospinning period proceeds [49].This process has been used to produce metal oxide/ceramic nanofibers in recent years, such as titanium oxide, barium titanate, lead zirconate titanate, silica, zirconia, titania, nickel oxide, barium titanate, lead zirconate titanate, and other oxide-containing materials [50].The majority of fibrous materials derived from natural and synthetic polymers are produced using electrospinning and similar processes (Figure 2) [51].
to overcome the surface tension and viscous drag force of the polymer solution [49] (Figure 1).As a result, a stream of fluid freely emerges from the needle, subdividing into millions of nano-to submicron-sized jets that deposit as nanofibers on the counter electrode or aluminum foil.This sheet is made up of randomly arranged fibers, with the thickness increasing as the electrospinning period proceeds [50].This process has been used to produce metal oxide/ceramic nanofibers in recent years, such as titanium oxide, barium titanate, lead zirconate titanate, silica, zirconia, titania, nickel oxide, barium titanate, lead zirconate titanate, and other oxide-containing materials [51].The majority of fibrous materials derived from natural and synthetic polymers are produced using electrospinning and similar processes (Figure 2) [52].(Figure 1).As a result, a stream of fluid freely emerges from the needle, subdividing into millions of nano-to submicron-sized jets that deposit as nanofibers on the counter electrode or aluminum foil.This sheet is made up of randomly arranged fibers, with the thickness increasing as the electrospinning period proceeds [50].This process has been used to produce metal oxide/ceramic nanofibers in recent years, such as titanium oxide, barium titanate, lead zirconate titanate, silica, zirconia, titania, nickel oxide, barium titanate, lead zirconate titanate, and other oxide-containing materials [51].The majority of fibrous materials derived from natural and synthetic polymers are produced using electrospinning and similar processes (Figure 2) [52].

Melt Electrospinning
Melt electrospinning (ME) is used to produce fibers using polymers that are difficult to dissolve in solvents prior to electrospinning, examples of which include polyethylene (PE), polypropylene (PP), and polyphenylene sulfide (PPS) [52,53].Conventional ME equipment includes a supply zone, electrical heating components, a conductive collector, and a highvoltage power supply.During melt electrospinning, a melted polymer is extruded through the spinneret, and a high voltage potential is applied between the collector and spinneret, ejecting a charged jet [54].The polymer jet is then extended toward the grounded collector, where it swiftly hardens, generating ultrafine solid fibers [55].The ME process is primarily influenced by polymer flow velocity, polymer structural properties, drawing temperature, and voltage [56].Melt spinning reduces production costs and enables fine control of fiber deposition.The number of polymers suitable for ME, on the other hand, is substantially smaller than for solution electrospinning.ME has only been tested on a few commercially available polymers [57].

Near-Field Electrospinning
Near-field electrospinning (NF-ES) is a simple approach for accurately controlling the locations of deposited fibers that need organized or pre-designed nanoscale fibrous structures [58].During the NF-ES technique, the probe tip is used to dip the liquid polymer solution or is typically placed near the collector.Using molten polymer from a distance reduces the required voltage and instability in bending during spinning, enabling the precise deposition of fibers with excellent spatial definition on a 3D motion platform [59].The ability of NF-ES to build (2D) and (3D) structures has been proven, expanding the potential use of fibers in domains such as energy harvesting and tissue engineering [60].Indeed, NF-ES has several benefits over conventional electrospinning, including a lower applied voltage and material usage, as well as position-controlled fiber deposition in the three axes, namely, the X, Y, and Z axes [52].Additionally, the fibers produced with NF-ES are often thicker than those produced with standard electrospinning [61].

Coaxial Electrospinning
For coaxial electrospinning, the setup is mostly the same as for electrospinning with one exception: the use of a coaxial needle, which consists of two concentric aligned hollow needles [62].Using two syringe pumps, two polymeric solutions are injected independently through the outer and inner needles.Nanofibers with regulated core and sheath layer compositions may now be made using coaxial electrospinning [63].Many substances, including proteins, oils, and medications, have been electrospun as the main structure for core-sheath nanofibers (Figure 2) [64].Coaxial electrospinning is another method for producing hollow nanofibers [65].One of the most important techniques for creating core-sheath nanofibers is emulsion electrophoresis [66].This improved electrospinning technology reduces the branching and splitting of spinning jets by injecting a magnetic field that balances out the forces that induce instability, leading to more uniform nanofibers and regulated deposition [67].Furthermore, when the jet reaches the substrate, the magnetic field increases its velocity as well as the internal alignment of the polymer network, resulting in a reduction in fiber diameter.These are suitable for producing nanofibers in parallel along magnetic field lines for biomedical purposes [68].

Solution Blow Spinning
Solution blow spinning (SBS), a method rooted in gas-assisted fiber manufacturing technology, has garnered significant attention in recent years due to its high productivity and adaptability [69].This approach proves particularly advantageous for spinning fibers from materials possessing low electrical conductivity, which poses challenges in the electrospinning process.In the literature, SBS has several names including air spinning, solution blowing, pressure-driven spinning jet spraying, and solution spraying [70].Its fundamental setup comprises concentrated nozzles, a compressed gas supply (such as air, nitrogen, synthetic air, or oxygen), a fiber collection system, and an infusion pump regulating the polymer ejection rate in a whirling configuration (i.e., similar to a thread-milling motion).
The polymer solution is driven through the inner nozzle with SBS, resulting in the production of a droplet at the inner nozzle's tip, which is stretched by the high-pressure compressed gas stream flowing through the outer nozzle [71].The pressurized air exiting the nozzle shapes the drop's surface into a cone, similar to Taylor's cone in electrospinning.When the critical air pressure is attained, surface tension forces are overcome, and a jet blasting from the cone's tip is driven toward the collecting target.As the jets traverse the environment (across the working distance), the polymer liquid undergoes stretching while the solvent rapidly evaporates.This process results in the formation of a web comprising micro-and nanofibers that are collectible on various surfaces, including living tissue, sheets, membranes, liquid surfaces, and rotating drums [72] (Figures 2 and 3).
ning.When the critical air pressure is attained, surface tension forces are overcome, and a jet blasting from the cone's tip is driven toward the collecting target.As the jets traverse the environment (across the working distance), the polymer liquid undergoes stretching while the solvent rapidly evaporates.This process results in the formation of a web comprising micro-and nanofibers that are collectible on various surfaces, including living tissue, sheets, membranes, liquid surfaces, and rotating drums [73] (Figures 2 and 3).

Force Spinning
Force spinning (FS), also known as rotary spinning or rotating jet spinning, has advanced significantly.Centrifugal spinning is a simple and controlled procedure for producing fibers by utilizing centrifugal forces (Figure 2) [74].Centrifugal forces overcome the surface tension and viscosity of a molten polymer or polymer solution injected via the valve in this approach, resulting in the ejection of a jet, which is then expanded and stretched by the air vortices [75].The solvent evaporates and the filament hardens during this phase, resulting in the formation of fibers that are placed on the collector's desk.Fluid viscoelasticity and the size of the nozzle, its rotational speed, its length, its construction, and the distance between it and the collector are all important factors and may all be adjusted to alter the shape and diameter of centrifugally spun fibers [76].Centrifugal spinning, similar to electrospinning, uses a diverse set of polymers and solvents.Also, high voltage is not required, and the method has significant industrial scaling potential.One corporation has produced industrial centrifugal spinning equipment that is speedier than electrospinning-based industrial setups [77].Given the fact that centrifugal spinning and SBS provide greater fiber yields, using these techniques to prepare nanofibers with a range, such as core-sheath or designed nanofibers, offers a challenge [78].

Force Spinning
Force spinning (FS), also known as rotary spinning or rotating jet spinning, has advanced significantly.Centrifugal spinning is a simple and controlled procedure for producing fibers by utilizing centrifugal forces (Figure 2) [73].Centrifugal forces overcome the surface tension and viscosity of a molten polymer or polymer solution injected via the valve in this approach, resulting in the ejection of a jet, which is then expanded and stretched by the air vortices [74].The solvent evaporates and the filament hardens during this phase, resulting in the formation of fibers that are placed on the collector's desk.Fluid viscoelasticity and the size of the nozzle, its rotational speed, its length, its construction, and the distance between it and the collector are all important factors and may all be adjusted to alter the shape and diameter of centrifugally spun fibers [75].Centrifugal spinning, similar to electrospinning, uses a diverse set of polymers and solvents.Also, high voltage is not required, and the method has significant industrial scaling potential.One corporation has produced industrial centrifugal spinning equipment that is speedier than electrospinning-based industrial setups [76].Given the fact that centrifugal spinning and SBS provide greater fiber yields, using these techniques to prepare nanofibers with a range, such as core-sheath or designed nanofibers, offers a challenge [77].

Microfluidic Spinning
Microfluidic spinning is a cost-effective approach for producing fibers with varied shapes and compositions at the micro-and nanoscale, which has been used over the last decade [78].In this technique, two different fluids-the fluid, which helps in fiber extrusion, and the core fluid, a polymer precursor solution-are equally injected into microscale channels through different input ports, resulting in a 3D coaxial flow at the channel crossover.Using photopolymerization, chemical or ionic crosslinking techniques, etc., the core fluid is solidified to create fibers [79].
The microfluidic spinning of nanofibers involves the use of microfluidic devices to precisely control the fabrication of nanofibers with diameters on the nanometer scale.This innovative technique harnesses the principles of microfluidics, a field focusing on manipulating small amounts of fluids within microscale channels, to produce high-quality and tailored nanofibers.The process typically involves the controlled flow of polymer solutions or melts through microchannels, where the fluid encounters shearing forces, electrostatic fields, or other relevant mechanisms.By manipulating the flow rates, compositions, and channel geometries within the microfluidic device, it becomes possible to precisely regulate the size, structure, and composition of the resulting nanofibers.Microfluidic devices enable precise control over the flow of materials, allowing for the creation of nanofibers with specific diameters, morphologies, and functionalities.The technology can be scaled up for mass production while maintaining uniformity and quality in nanofiber products [80]).Various polymers, nanoparticles, and functional materials can be used in microfluidic spinning, providing versatility in producing nanofibers for diverse applications, including biomedical, filtration, tissue engineering, and more.Microfluidic platforms can facilitate the creation of composite or multicomponent nanofibers by mixing different materials within the microchannels, offering enhanced functionalities and tailored properties.Microfluidic techniques allow for precise control over the alignment, patterning, and spatial arrangement of nanofibers, enabling the creation of complex structures and architectures.
The microfluidic spinning of nanofibers holds significant promise in advancing various fields due to its ability to produce nanofibers with controlled characteristics and tailored properties, fostering innovation in numerous applications across industries such as healthcare, textiles, filtration, and beyond.

Modification of Polymer Nanofibers
Although the opacity of polymer nanofibers is beneficial, some pure polymers still have limitations in the adsorption process due to their higher opacity [81].Polyacrylonitrile (PAN) [5] and nylon are examples of materials that have little adsorption capacity for the removal of pollutants; PVA, polyacrylic acid (PAA), and polyvinyl pyrrolidone (PVP) are examples of materials that are unstable in aqueous solutions; and chitosan is an example of a material with subpar mechanical properties [36,53,81].Scientists have put a lot of effort into improving the properties of nanofibers with surface modification to solve these problems.Surface modification aims to improve the mechanical characteristics, hydrophilicity, and wettability of nanofibers in aqueous solutions, as well as their adsorption sites on the surface [82].Nanocomposites and blends, which are one-step treatments applied during electrospinning and post-treatments applied after electrospinning, are two ways to modify the surface of nanofibers.

Scaffolds
A biodegradable scaffold is often used in the engineering of living tissues.Before physiologically active tissue or natural extracellular matrix (ECM) can regenerate, a scaffold is used as a temporary template for cell seeding, proliferation, and differentiation

Scaffolds
A biodegradable scaffold is often used in the engineering of living tissues.Before physiologically active tissue or natural extracellular matrix (ECM) can regenerate, a scaffold is used as a temporary template for cell seeding, proliferation, and differentiation [87].For making tissues including cartilage, heart, neurons, bones, arterial blood arteries, and other structures, polymer nanofibers have been proposed as scaffolds [88].The most common fabrication method for these scaffolds right now is electrospinning.Electrospun natural and synthetic polymer nanofibers were used to produce scaffolds [89].
The following are the benefits of using electrospinning to produce tissue scaffolds: (1) Electrospinning is able to generate ultra-thin fibers with diameters ranging from several micrometers to a few nanometers.( 2) Electrospinning is customizable in a wide range of mono-polymer and polymer compositions with certain other materials.A large number of studies have been published in the last two decades that analyzed fibrous scaffolds in tissue engineering for a variety of applications, including neural, tissue regeneration, bone, and cartilage [90,91], which are discussed in detail below.

Regeneration of Bone
Bone is an interactive tissue composed of organic and inorganic components arranged in a hierarchical structure [92].When bone tissues are affected, the damage depends on the size.Bones can self-heal; however, if the damage is severe, therapeutic procedures to repair the damaged tissue are required.Repairing critical-sized bone lesions remains difficult [93].In bone healing treatments, a variety of biomaterials have been used.Both manufactured and natural nanofibrous composites have been created.Much research has been performed in the field of medicines to control inflammatory responses and speed up bone regeneration.The tiny pore width inherent in spinning two-dimensional (2D) structures is less than that recommended for cell proliferation and bone engraftment, which is true for traditional spinning techniques, especially electrospinning.In recent years, efforts to produce 3D nanofibrous structures have included extending spinning duration, post-processing of as-spun fibers, using 3D collectors or liquid collectors, and merging electrospinning and additive manufacturing principles.The utilization of different synthesis techniques has produced a polymer nanofiber that helps in bone regeneration [94].

Cartilage Regeneration
Cartilage regeneration remains difficult, considering a tissue's limited inherent regenerating ability.Microfracture and tissue transplants are two of the many treatment approaches being researched for cartilage regeneration (decellularized structures, allograft, xenograft, and autograft) [95].However, these therapies have a limited ability to stimulate complete cartilage tissue healing.Spun-fiber scaffolding has emerged as a potential alternative in tissue engineering for healing complicated tissues such as cartilage.Creating stimuli-responsive hierarchical three-dimensional polymeric frameworks for temporally bioactive delivery chemicals targeted at influencing cell activity can lead to significant advances in cartilage regeneration [96].These scaffolds should also have a suitable pore for cell infiltration and migration throughout the tissue repair process.Electrospinning is the most commonly used technology for fabricating [97].

Use in Peripheral Nerve Regeneration
Traumatic or infectious peripheral nerve injuries frequently demand the use of nerve transplants to guide the axon from the basic to the distant nerve endings [98].Autografts are now the most common approach for nerve regeneration; however, they have drawbacks such as scarcity and possibility of neuroma development.Peripheral nerve injuries are extremely prevalent in clinical practice and can result in profound neurological impairments and neuropathic pain.The nervous system's limited regenerating ability makes treating nerve damage difficult.The current clinical protocol for treating nerve damage is the use of a nerve autograft, although this treatment technique has certain limitations, including a lack of donor nerve availability and donor-site morbidities [99].Polymeric nanofibrous nerve conducts coupled with biochemical and physical signals are offered as possible solutions for nerve autografts.Bioactive components such as extracellular matrix (ECM) peptides and cell growth factors components have been introduced into aligned-spun polymeric fiber scaffolds, which have shown tremendous potential for nerve regeneration [100].

Regeneration of Ligaments and Tendons
Repair of ruptured/torn ligaments is one of the most popular surgical operations [101].Furthermore, tendon damage is the most prevalent injury among people.Autografts have been regarded as the gold standard for anterior cruciate ligament (ACL) rupture restoration and tendon repair for several decades; however, allograft tissue is also widely used [102].Tissue grafts have a high success rate; nevertheless, they have drawbacks.As a result, tissue engineering has emerged as an alternative strategy with the use of specially constructed cells, scaffolds, and cells [103].Using a unique therapeutic technique to assist and expedite the repair of a torn rotator cuff, one research group created an electrospun PLGA nanofibrous scaffold in their lab.An innovative animal model test was performed to test the efficiency of the PLGA nanofibrous scaffold in accelerating the healing rate of a tendon lesion [104].

Regeneration of Cardiovascular
Cardiovascular illnesses are the major cause of mortality worldwide, and their prevalence has risen dramatically in recent decades.Myocardial infarction, excessive blood pressure, coronary artery disease, valve problems, and cardiomyopathy are the most common ailments that can lead to heart failure [105].Over the last years, cardiac tissue engineering technologies based on 3D fiber scaffolds have emerged as a viable tool for regenerating injured heart tissue.Numerous spinning techniques, including microfluidic spinning, electrospinning, etc., have been used to build scaffolds for myocardial, valve, and vascular tissue repair [106].

Dressings for Wound Healing
The skin protects the internal organs, regulates body temperature, and performs metabolism, immunologic, sensorial, and thermoregulatory functions [107].When the anatomic structure of the skin is disrupted due to accidents or chronic illnesses, wound dressing is usually used to encourage skin regeneration in the affected area.The market today offers a wide range of wound dressings consisting of foams, sponges, and hydrogels.Nanofibers made with unique technologies have exceptional wound-healing abilities.Their organization is quite similar to the ECM structure of the human body and promotes cell growth, division, and adhesion.Simultaneously, the strong porosity and absorption rate may absorb wound exudate and keep the environment moist for healing [108].Moreover, the large surface area facilitates the loading and transporting of bioactive components such as medicines and growth regulators much easier and helps in the protection of the wound from external infections.In that aspect, electrospun nanofiber materials are regarded as the best option for wound dressings.Improved hemostasis and better dressing flexibility are two major needs for totally covering problematic wounds, both of which are achieved by nanofibrous dressings [109].Additionally, from an aesthetic point of view, nanofibers provide the superior benefit of wrinkle-free regeneration.

Dental Restoration Nanocomposites
Polymer nanofibers are utilized to enhance composite dental materials.A dental restorative composite is typically composed of a dental resin such as 2,2 ′ -bis-[4-(methacryloxypropoxy)-phenyl]-propane (bis-GMA) and tri-ethylene glycol dimethacrylate (TEGDMA) as well as the specified number of fillers [110].In fact, it has been shown that fillers, which were originally utilized to improve mechanical qualities, might eventually have a failure in increasing destruction.The use of nanofibers as reinforcement for com-posites has only offered slight improvements in strength and stiffness so far [111].The advantage of using nanofibers when the fiber diameter is smaller than the wavelength of visible light is that there is no detrimental impact on the transparency of the manufactured composite dental device.Polymer nanofibers are thus extremely intriguing choices for the future creation of lightweight, optimal mechanical qualities, and desirable aesthetic aspects in orthodontic composite devices [112].

Controlled Drug Release
Controlled delivery of therapeutic drugs to particular targets over time has been hailed as a potential technique for addressing the limitations of systemic administration by increasing the therapeutic index while lowering severe side effects [113].The effectiveness of the drug-delivery method is largely determined by the drug carrier used, which should ideally have excellent drug loading efficiency, biocompatibility, efficient cellular absorption, and the ability to keep drug concentrations within a therapeutic window [114].Drug or pharmaceutical agent administration to patients in a biologically appropriate manner has long been a major challenge.New materials and technology have a significant influence on pharmacy [115].Numerous synthetic, natural, and polymer-blend combinations have been thoroughly studied for the creation of nanofiber-based methods.Polymeric microand nanofibers have lately gained considerable interest for enormous material diversity, ease of fabrication, and drug encapsulation [116].

Medical Implants
Nanofibers have been used for vascular and breast prostheses since the early 1980s.US patents on fabrication processes and procedures for these prostheses have been issued, and vascular prosthetics are available [117].Polymer nanofibers have recently been used in several types of medical prostheses, for example, a thin porous covering of electrospun submicron protein fibers was applied to a prosthesis implantable into the central nervous system.It is anticipated that coating film with a gradient fiber structure would efficiently minimize stiffness mismatch at the tissue to avoid device failure.It serves as an interphase between the nervous system and the device [118].Adhesion has become a typical source of complication following abdominal treatment, which includes a small intestinal blockage, chronic severe pain, female infertility, and trouble in future operations.According to past studies, the membrane can reduce adhesion following surgery and can result in a physical barrier and medication delivery mechanism [119].The outcome, the capacity to modify the composition, drug loading capabilities, and the ease of handling make these nanofibrous membranes perfect candidates for future clinical trials.

Cancer Therapy
The administration of anticancer drugs (both oral and intravenous administration) has several disadvantages, including limited effectiveness, low solubility, low stability, side effects on healthy tissues, the necessity for many injections, and a high rate of clearance by the reticuloendothelial system [120].Scientists have been working with a variety of approaches to reduce the number of undesired side effects on healthy tissues, increase efficiency, and provide a longer duration of function, including restricted and continuing postsurgical drug administration.Anticancer drug mixtures with electrospun nanofiber scaffolds can compensate for these disadvantages and can be readily inserted into solid tumor sites [121].This not only provides a high local dose by including small quantities of the medicine, but it also lowers the need for frequent administrations, allowing patients to be more comfortable and have an effective recovery.

Biosensors
Biosensors, which generally include a bi-functional membrane and a transducer, are widely used in environmental, food, and healthcare applications.Sensitivity, selectivity, reaction time, repeatability, and aging are all the parameters that impact sensor performance and are directly reliant on many properties [122].Sensors are particularly significant since there is a high need for low-concentration gas and biological material detection.Increasing sensitivity will need the use of sensor films, opening the door for polymer nanofibers to be used as biosensors [123].Early disease diagnosis and monitoring are crucial components of patient therapy, and this procedure is developing reliable sensors for disease markers.Because of their enormous surface area-to-volume ratio and diversity in structure and composition, nanofibers have piqued the interest of many in the building of sensing platforms in recent years [124].Nanofiber-based wearables have become a popular and potential technique for keeping track of physiological data such as pulse rate, breath humidity, respiration, and muscle movements.The increasing demand for these nanostructured materials is due to their fabrication and low cost, dependability, and biodegradability as well as adequate mechanical qualities and short reaction time.Several research studies have shown that nanofibers offer considerable promise for health.However, commercial adoption has been more difficult due to the lack of techniques that merge production speed and accuracy to make economical, sensitive, and selective sensors.
Electrospun nanofibers have applications in safety gear, improved composites, photovoltaic cells, and medical technologies [125].Some nanofibers, like carbon fibers, polyacrylonitrile, nylon, and polyurethane (PU), have the potential to be used for heat insulation.Because micro-nano pores characterize electrospun ceramic nanofibers, they are best suited for the removal of microparticles.Electrospun nanofiber membrane features make them appropriate for use as filters in conservation biology [126].Other characteristics include a large surface area, high aspect ratio, and permeability.These characteristics are used in the manufacture of a variety of products, including gas storage units, tissue engineering scaffolds, bioreactors, electric as well as optical devices, optical optics, and fluidic elements gadgets.

Advantages and Disadvantages of Polymer Nanofibers
Nanofibers possess an extremely high surface area compared with their volume, which makes them excellent for various applications such as filtration, catalysis, and energy storage [12,[18][19][20][21][22][23][24].The presence of a large surface area allows for enhanced interactions with other substances, leading to improved efficiency.Additionally, they exhibit exceptional mechanical properties such as high strength and flexibility and can be stretched and bent without breaking easily, making them suitable for applications where durability is required, such as reinforcement materials in composites or tissue engineering scaffolds [109][110][111][112][113][114].Their small pore size prevents the passage of unwanted materials while allowing desired molecules to permeate, making them useful in protective clothing, packaging, and biomedical applications.Along with this, nanofibers can be easily modified or functionalized by incorporating additives, nanoparticles, or chemical groups onto their surfaces.This huge versatility allows for the creation of tailored properties and functionalities, enabling applications in areas such as drug delivery.Nanofibers can be fabricated from a wide range of materials, including polymers, ceramics, metals, and carbon-based materials.This versatility allows for the development of nanofibers with diverse properties and opens up possibilities for applications in various fields.Some nanofibers, such as carbon nanotubes and graphene-based nanofibers, exhibit excellent electrical and thermal conductivity.These properties make them suitable for applications such as flexible electronics, energy storage devices, and thermal management systems.Nanofibers can be engineered to release substances in a controlled manner.By incorporating drugs, fertilizers, or other active compounds into nanofiber matrices, controlled release systems can be developed for targeted delivery and prolonged therapeutic effects [103][104][105]127,128]. Regardless of the fact that solution electrospinning has been the focus of several scientific disciplines because of its high adaptability, simplicity, and economical processing equipment, significant hurdles remain for its industrial uses [129].First, using organic solvents in electrospinning poses financial and ecological challenges.Furthermore, a few of the remaining electrospun solvent materials might be hazardous, restricting their usage in biomedical applications [130].The classic solution electrospinning method is also expensive, and the poor productivity rate of produced nanofibers is an additional drawback [131].

Conclusions and Future Perspectives
The electrospinning of polymer nanofibers has emerged as a transformative technique with immense potential in the realm of biomedical applications.This method allows for the fabrication of nanoscale fibers using electrostatic forces, resulting in materials with unique structural, mechanical, and functional properties.The versatility of electrospun polymer nanofibers has led to a significant advancement in various biomedical fields, including tissue engineering, drug delivery, wound healing, and regenerative medicine.Electrospun nanofibers have been explored for regenerating diverse tissues, ranging from skin and bone to cartilage and nerves.Their high porosity and tunable mechanical properties facilitate nutrient diffusion and mechanical support, enabling successful integration with host tissues.The biomedical application of electrospun nanofibers extends to controlled drug delivery.These nanofibers possess a high surface area-to-volume ratio, allowing for efficient encapsulation and sustained release of therapeutic agents.Electrospun nanofibers have shown potential in delivering a wide range of drugs, including antibiotics, antiinflammatory agents, and growth factors, for applications such as wound healing and cancer treatment.
In conclusion, the electrospinning of polymer nanofibers stands as a pioneering technique with substantial implications for the biomedical field.Its contributions to tissue engineering, drug delivery, and regenerative medicine have already showcased its transformative potential.The potential of electrospun nanofibers is incredibly promising, and they are on the brink of transforming various industries.In the medical field, they offer possibilities for personalized regenerative treatments and targeted drug administration.Industries focused on the environment could see improved filtration and pollutant eradication, and there is also excitement about their role in advancing energy storage and wearable tech.As researchers delve deeper into understanding nanofiber behavior and optimizing fabrication techniques, the future promises even more exciting developments, potentially revolutionizing healthcare and improving the quality of life for countless individuals worldwide.

Figure 1 .
Figure 1.Electrospinning instrument parts and its mechanism for synthesizing nanofibers.

Figure 1 .
Figure 1.Electrospinning instrument parts and its mechanism for synthesizing nanofibers.

Figure 1 .
Figure 1.Electrospinning instrument parts and its mechanism for synthesizing nanofibers.

Figure 4 .
Figure 4. Application of nanofibers in the field of medicine, drug discovery, sensors, and tissue engineering.

Figure 4 .
Figure 4. Application of nanofibers in the field of medicine, drug discovery, sensors, and tissue engineering.

Author Contributions:
Conceptualization, S.J. and B.A.V.M.; writing-original draft preparation, B.A.V.M. and S.J.; writing-review and editing, S.J., B.A.V.M. and M.K.; visualization, supervision and project administration, illustrations, and figures, S.J.All authors have read and agreed to the published version of the manuscript.Funding: Nagasaki University, Japan.Data Availability Statement: Not applicable.