The use of nanofiber materials for tissue engineering and regenerative medicine applications is a growing trend as they provide improved support for cell proliferation and survival due in part to their morphology mimicking that of the extracellular matrix (ECM). Electrospinning is the most common technique nowadays used to produce polymeric nanofiber materials because of easy fabrication and low cost production.

Definition of nanofiber

The history of nanofibers starts with Anton Formhals who is also known as the inventor of electrospinning. Between the years 1933 and 1944 he conducted many experiments that resulted in nanofiber production and at least 22 patents on electrospinning. In 1966 professor Harold Simons published a patent for patterned nonwoven nanofiber fabric production by using electrospinning.

In 1969 Sir Geoffrey Ingram Taylor studied the mechanism that regulates the fluid cone formation and published a few studies about the theoretical model of the electrospinning process. The cone was later called ‘the Taylor cone’ after him. In 1971, electrospinning device capable of fabricating acrylic nanofibers was invented by professor Peter K. Baumgarten. He was the first one to investigate how different parameters such as polymer solutions, viscosity and voltage affect fiber diameter size. 2005 was the year when so called ‘nanospider technology’ was born, a needle-free electrospinning process that allows Taylor cone formation from a thin film of a polymer solution.

Nanofibers are a novel, unique and constantly evolving class of materials that have found a broad range of applications. They possess excellent properties, mostly because of their extremely large surface area to volume ratio, which could lead to new composite material design, manufacturing and applications. High porosity, low density and tight pore size are just some of special properties that nanofibers exhibit. Nanofibers have small diameters and are lightweight compared to microfibers.

Nevertheless, their diameters almost match the scale size and morphology of extracellular 3-D matrix (ECM) perfectly, making them suitable material for tissue scaffold fabrication. Nanofibers are obtained from various polymers in a filament form, thereby exhibiting different mechanical, physical and chemical characteristics with diverse prospective applications. Studies have also revealed that mechanical properties such as Young’s modulus, tensile strength and shear modulus increase with a decrease in nanofiber diameter size .

Nanofibers are fibers with a diameter size up to 100nm and are produced from natural and synthetic polymers. However, the term ‘nanofiber’ in tissue engineering refers to those fibers with diameter size in the range between 1 and 1000nm. The diameter primarily depends on the used polymer solution and the production technique.

With nanofiber diameter size come different and unique physicochemica properties such as previously mentioned high surface area to volume ratio, pore size and interconnected pore structure that enhances protein adsorption, cell adhesion, proliferation and migration as well as the nanofiber ability to be functionalized with some other molecules. Nanofiber mechanical properties like tensile strength and stiffness are the upper-class in comparison with the mechanical properties of other material forms.

One of the biggest challenges in tissue engineering and regenerative medicine is developing a scaffold that will mimic the framework of the extracellular matrix at the nanometer scale. Nanofibers have small diameter that closely matches the one of extracellular matrix fibers as well as porous structure that provides support for cell proliferation and survival due, in part, to their morphology mimicking the architecture of the ECM, ability to be functionalized and higher rates of protein adsorption which is the key mediator in cell attachment to a biomaterial surface.

Polymeric nanofibers can be produced using various mechanical and chemical techniques. Nowadays, nanofibers are mainly produced via electrospinning and collected in nonwoven form. It is a powerful and effective yet simple and time and cost-effective method that provides long continuous nanofibers with a diameter size from 10nm to a few hundred nm. The technique was first introduced in 1934 when Formhals patented the process.

The method is based on a high voltage applied to a polymer solution or a melt extruded through a needle and electrostatic repulsion of the charged polymer solution jet that becomes starched and forms filaments when the repulsion is higher than the surface tension of the solution. Careful and appropriate selection of all parameters including applied voltage, solution feed rate, needle diameter, needle-collector distance, polymer solution chemical characteristics and parameters as well as ambient factors have to be made when fabricating nanofibers as each one of them will have an effect on the structure, morphology, geometry, size and physic-chemical properties of electrospun nanofibers.

Nanofiber technology is one of the fastest growing scientific disciplines that has promising potential for use in various fields, such as biomedical and tissue engineering, regenerative medicine, environmental sciences, drug delivery, cancer diagnosis, filter media, textile, energy sector, information technology and many other. Polymer nanofibers ability to form composites and be reinforced with nanoparticles has resulted in electrospun nanofibers with some unsurpassed features and properties that are not even exhibited in microfibers.

Nanofiber composites and their applications

In recent years, electrospun composite nanofibers have been one of the top-trending research topics that has showed abundant potential for applications in various disciplines. The history of nanocomposite materials starts in the late 1970s and the early 1980s when Toyota developed a nanocomposite material called nanoclay-polyamide (Nylon-6) that was made of nylon mixed with nanoclays and had remarkably increased strength and heat resistance comparing to regular polymer. Nanocomposites consist of at least two distinct phases of which minimum one of them has length scale in the dimension of nanometer range (10-9m).

They are simple and easy to fabricate through electrospinning technique in order to produce electrospun nanofibers of blended multicomponent solution. With the diameter in nanometer range scale, large surface area, controllable porosity and the possibility to tailor-make their chemical, physical, mechanical and electrical properties, nanomaterials in combination with other materials provide unique, specific, improved and superior characteristics. Nanocomposites are classified based on their matrix materials and reinforcement materials.

Nanocomposites classification

The choice of employed matrix and reinforcement material will depend on the applications. The idea of reinforced polymer nanocomposites fabrication is to produce a polymer matrix with fillers that has superior, improved and increased mechanical properties, including stiffness, toughness, Young’s modulus and tensile strength that would not be achieved nor exhibited at the micro/macroscopic scale. The fillers can exist in either nanotube or nanoparticle form. Properties change of materials at the nanoscale is primarily because of the improved phase-interface interactions.

Nowadays, nanoscale fillers such as silver nanoparticles (AgNPs), graphene, zinc oxide (ZnO), titanium dioxide (TiO2), single and multi-walled carbon nanotubes (SWCNT and MWCNTT) are some of the most common fillers being incorporated into the polymer solution to form blended composite solutions that consist of both, organic and inorganic materials with the intention of producing electrospun composite nanofibers with enhanced properties.

Up to date, nanocomposites are used in a broad range of applications, ranging from various biological, dental, medical and biomedical applications to food processing, energy storage, defense system, information industry and many more. The utilization of reinforced nanofibers is significantly noticeable in developing of biomimetic scaffolds (for tissue engineering) that are capable of providing cell support, adhesion, differentiation, proliferation and migration. Scaffolds can be fabricated via different techniques, including:

  • Phase separation (high porosity; simple; can be combined with other techniques);
  • Gas foaming (porosity and pore size controlled; high porosity);
  • Freeze drying (pore size controlled by pH and freezing rate);
  • Self-assembly (closed system; well controlled porosity, pore size and fiber diameter);
  • Electrospinning (can create aligned nanofibrous mats even with biological polymers; simple).

Electrospinning is a simple, cost-effective and one of the most common and traditional methods to produce electrospun scaffolds. At the same time, it is a promising technique for biomimetic fibrous porous tissue-engineered scaffolds production. It allows a wide variety of biocompatible polymers to be processed and electrospun into fibrous scaffolds. Organic-inorganic hybrid electrospun nanofibers, composed of organic polymer and inorganic nanoparticles, have attracted increasing research attention of scientists and engineers essentially because of their unique characteristics such as flexibility and lightweight which come from polymer and ability to be functionalized and tailored to fulfill needs for specific applications, advantages coming from inorganic nanoparticles.

One of the most well-known polymers used for tissue regeneration is polylactic acid (PLA). In a study conducted by Szczypta et al., this biodegradable polymer was reinforced with CNT to provide enhanced biological and mechanical properties of scaffolds. In another study PAN/Fe(III) metal-organic based electrospun fibrous nanocomposite was fabricated. In vitro studies carried out on human umbilical vein endothelial cells (HUVEC) seeded onto scaffolds, demonstrated that the fibrous nanocomposite fibers were non-toxic and are biocompatible with undisturbed cell adhesion and proliferation. In vivo studies showed no inflammatory response.

 

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