*3.2. Biomedical Applications of Sputtered Electrospun Polymer-Based Nanofibers*

Plasma technology can be used to improve the surface properties of polymers without changing their bulk characters. Plasma-treated polymers have found wide application in diverse fields, such as the automobile, microelectronics, chemical and biomedical industries [121]. Polymer surface properties such as hydrophobicity, roughness, chemical structure, conductivity, etc. can be modified for various applications. Plasma treatment can affect the polymer surfaces through micro-etching, organic contamination, cross-linking, surface chemistry modification, and surface coating with a specific target material [122]. The biomaterials should possess good mechanical and surface characteristics that are appropriate for the biological environment. For instance, for cell adhesion, the polymer surface should have low surface free energy, surface roughness, and hydrophilicity. Plasma treatment via magnetron sputtering technology has been implemented to coat the surfaces of polymers to form biomaterials suitable for biomedical applications such as antibacterial, biocompatibility, and tissue engineering.

Plasma sputtering technology includes both thermal and non-thermal deposition processes. However, non-thermal deposition processes are highly recommended for polymers, because they do not damage the bulk properties of the polymer. Magnetron sputtering is the technique used for coating the polymer surface. Magnetron sputtering is a technology that was developed during the 1970s, and it is a high-speed and low-temperature technique for preparing a strong and uniform adhesion film on the surface of polymers, ceramics and composite materials [123]. However, argon gas is commonly used, because it does not damage the target due to its nobility. The full process is quick and requires only a low temperature, while offering a high film forming rate and strong film adhesion [124]. For instance, composite microfibers of Poly(methyl methacrylate)/organically modified montmorillonite (O-MMT) were manufactured by electrospinning with the incorporation of emulsion polymerization [125]. Here, the prepared composite microfibers of PMMA-O-MMT were magnetron sputter-coated with Titanium dioxide (TiO2). The results showed that the deposited anatase-TiO2 and rutile-TiO2 exhibited better surface wettability without damaging the PMMA-O-MMT compound. These composite fibers have a UV absorption of 254 nm. Therefore, it induces the photocatalytic degradation of the model compound methylene blue. Thus, these materials provide a promising application in dye wastewater treatment.

Polymer microspheres [126], thin films [127], and fibers [128] have been coated with Ag [107,108,129], Cu [130], Ti [131], TiO2 [132], gold (Au) [133], hydroxyapatite (HAP), tricalcium phosphate (TCP) [134], amorphous calcium pyrophosphate (CPP) [134], and dicalcium phosphate dihydrate (DCPD) [134] for different biomedical applications.

#### 3.2.1. Antibacterial Coatings

The attachment of bacteria to the surface of a polymer can lead to the formation of biofilm. Therefore, biofilm-resistant polymers are an essential factor for the medical field. Biofilm resistance could be imbued in the polymer through the addition of antibacterial agents on the surface of the polymer to prevent bacterial adhesion. Materials such as medical textiles, wound dressings, prostheses and implant materials should display antibacterial activity for efficient biological activity. Antibacterial properties are an essential parameter to take into account for wound dressing. Antibacterial activities are promoted through the addition of some antibacterial components to the fabrics. There are many components, including both inorganic and organic (drugs), as well as metals. Inorganic agents include TiO2, carbon nanotubes, and Ag, Zn, ZnO2, Cu, Ga, and Au NPs [135]. Organic agents such as Triclosan inhibit the development of micro-organisms using electrochemical activity to disrupt their cell walls [136].

Among the inorganic antibacterial components, Ag NPs have been well studied [137]. Ag NPs were added to electrospun fibers via Ag ions through the wetting process [138,139], silver sulfaazide [93], etc. The wetting process for the addition of Ag to the matrix has many disadvantages, such as uneven distribution of NPs, use of reducing agents that are toxic, and the difficulty of controlling the size of NPs—depending on the strong and weak reducing agents used [140]. However, the most efficient way of introducing NPs to the surface of polymers or fabrics is by using plasma technology. Plasma technology provides more uniform deposition, less use of resources, and a simpler process for the coating of antibacterial material such as Ag, Si, Cu, etc., onto the surface of the polymer than the wetting process. Sputtering, known as physical vapor deposition, has been used effectively in the coating of a number of thin films for electronics applications. Therefore, sputter-coating of metals to enhance antibacterial properties can be performed with the addition of many target materials, including Ag, Ag/Si, Cu, Ti, etc. Therefore, more studies are required to compare the antibacterial properties of various materials incorporated in bioresorbable polymers.

### Silver (Ag)

Silver is a transition metal in the periodic table. Silver-related compounds or NPs have a biocidal effect on around 16 species of bacteria, because of its toxic effect on microorganisms [119,120,141,142]. Thus, silver is coated on medical devices for antibacterial applications [143]. At low concentrations,

Ag NPs show good antibacterial efficiency [144]. Moreover, the lack of toxic effect of Ag NPs on human monocytes cell lines indicates the possible application of Ag in the fabrication of medical devices.

The mechanism of antibacterial activity of Ag on microorganisms has not yet been well studied. It has been shown that, in *E. coli*, AgNP-treated bacteria exhibit some pits on the cell wall and an accumulation of Ag in the cellular membrane. This type of membrane exhibits an increase in permeability. Bacterial DNA loses its replication ability and cellular proteins and becomes denatured by binding Ag ions or NPs to the functional group of the protein [145]. On the other hand, some authors have reported that Ag NPs would denature the cellular proteins required for cellular nutrient transport and damage the cell membrane or cell wall, enhancing cell permeability and ultimately leading to cell death [142]. It has also been noted that the antibacterial efficiency of Ag depends on its shape. Ag NPs with a {111} lattice basal plane (representing the cubic structure lattice pattern) display more robust antibacterial action than spherical and rod-shaped NPs and silver ions [146].

Silver has excellent antibacterial properties. Silver treatment is well known for its application in wound dressing materials. The silver is incorporated as Ag NPs by introduction through AgNO3 using a reducing agent. However, this type of silver incorporation leads to burst release of silver from the material, resulting in a very high concentration of Ag in the wound. This is followed by the sudden reduction in silver because of both bacterial consumption and reaction with other compounds present in the wound beds, such as phosphates, chlorine, and proteins. Therefore, silver release in the wound should take place in a controlled manner. Also, the silver nitrate present is a hypotonic; hence, it can cause a strong electrolyte imbalance, which could damage the wound site and produce gross systemic inequality, which could kill patients with extensive burns who require large doses of silver. However, silver sulfaazide was developed in order to minimize the side effects of using silver nitrate. However, the removal of silver sulfaazide cream from the wound surface is performed by scraping, and this could result in a highly painful dressing procedure for the patients. Moreover, sulfaazide does not show any hypotonic effect. Therefore, it is necessary to develop a better process for delivering silver that is efficient, involves introduction over a prolonged period, acts against many ranges of bacteria, requires only a few changes of the wound dressing, and never interferes with the wound healing process. With this in mind, sputtering is a new field of surface coating of wound dressing materials for extended release of silver with potent antibacterial properties. The optimization of the sputtering process is an essential criterion for better antibacterial properties.

It is also noted that silver is the best candidate for wound curing applications, because it reduces inflammation [147], impedes contraction, and improves cell epithelialization [148]. Ag NPs exhibit cellular toxicity, and this leads to a decrease the biocompatibility of the scaffolds [149]. However, the amount of Ag in the scaffolds can be used to optimize the antibacterial effect and cellular toxicity of the Ag.

Antibacterial coatings on medical textiles are an important tool for avoiding infections during the surgical process [150]. Silver is coated onto textiles via different techniques. Silver-coated textiles are limited in application because of their reduced durability. Therefore, strong adhesion of silver on fabrics can be obtained by using the sputter-coating technique [150]. Cotton fabric with antibacterial properties could have a variety of applications. Silver is the most commonly used material for enhancing the antibacterial properties of cellulosic fibers [150]. Wet and dry methods can be used to incorporate silver particles. The wet method changes the bulk properties of textiles and also has a negative impact on the environment. However, dry processes such as sputter-coating are eco-friendly processes than only change the surface of the matrix. Therefore, Ag was incorporated into cotton matrixes of various thicknesses in order to study the antibacterial properties, the release of the Ag in water, etc. The results suggested that Ag shows antibacterial activity against *Staphylococcus aureus*, *Escherichia coli* and *Candida albicans* [150]. In addition, sputter-coating also improved the water contact angle of the cotton fabrics. Thus, antibacterial properties could be added to the nanofibers using the sputtering technique. Simultaneously, Chen et al. sputtered PET fabrics using high-power impulse magnetron sputtering, which provides a highly concentrated plasma, so that these fabrics will support adhered films [151]. Examination of antimicrobial activity revealed that a silver film that is deposited

for more than 1 min displays excellent bactericidal (>0) and bacteriostatic (>2.0) effects, based on JIS standards. Furthermore, the coated fabrics showed the capacity to retain antibacterial properties over 20 cycles of washing, indicating the long-term durability for the materials.

The wound dressing mats of polymer sheet and electrospun fiber scaffolds were sputter-coated with Ag and their antibacterial properties studied. Liu et al. examined the influence of magnetron sputter-coating of nanosilver on polyetheretherketone (PEEK) and investigated the resulting cytotoxicity and antibacterial properties [152]. PEEKs were sputter-coated with Ag 3 nm, 6 nm, 9 nm and 12 nm NPs (Figure 7). The antibacterial properties and bacterial adhesion to the surface were studied. Homogeneous nanosilver was coated on the surface; an increase in the water contact angle was observed, and there was no cytotoxicity for the CCK-8. In addition, the coating also provided excellent adhesion of bacteria to the PEEK and improved antibacterial activity towards *Streptococcus mutans* and *Staphylococcus aureus*.

**Figure 7.** (**a**) Schematic representation of PEEK film coated with nanosilver via sputter-coating; (**b**) SEM images of PEEK at different thicknesses of Ag (3, 6, 9, 12 nm); (**c**) Water contact angle of the coated thin film; (**d**) Antibacterial activity of the PEEK/Ag composite material. Reproduced with permission from [152]. Elsevier, 2017.

The combination of electrospinning and sputtering technology can result in many novel composite fibers with diverse applications in the biomedical field, such as for wound dressing mats with excellent biocompatibility and antibacterial properties. The electrospun microfibers were coated with Ag by DC magnetron sputtering [129]. The electrospun scaffolds of poly(glycerol sebacate)/poly(3-caprolactone) (PGS/PCL) were coated with Ag, and their antibacterial properties and silver release behavior were studied. PGS/PCL showed good mechanical and thermal behavior due to the increase in fiber diameter and the decrease in fiber pore size when sputter-coated with Ag. The fiber scaffolds demonstrated a gradual release of Ag, contributing to antibacterial activity. Therefore, this material could find appropriate application in wound dressing and bandages. Moreover, prosthetic implants also require antibacterial properties in order to avoid infection after surgery. With the objective of avoiding abdominal infections after implanting prostheses for hernia repair, Muzio et al. [153] prepared polypropylene prostheses coated with a silver-silica composite (Ag/SiO2) layer. The prepared mesh hernia prostheses (CMC) consisted of two layers of microporous light mesh and a thin transparent film of polypropylene. The Ag/SiO2 composite was sputter-coated onto the CMC meshes and the microporous mesh layer alone. The sputtering process was optimized via addition in order to test biocompatibility and antibacterial properties. In addition, it is noted that sputter-coating with CMC improved the antibacterial properties, but reduced biocompatibility. However, the sputter-coated meshes alone showed good antibacterial properties and biocompatibility. In addition, fiber meshes coated with Ag/SiO2 enhanced the growth of seeded fibroblast without causing apoptosis or necrosis of the fibroblast; in addition, the meshes also exhibited good antibacterial properties.
