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Muzafar Ahmad Kanjwal
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Sirius Huang
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Kanjwal, M.A.;  Ghaferi, A.A. Biomedical Applications of Electrospun Graphene Oxide. Encyclopedia. Available online: https://encyclopedia.pub/entry/35496 (accessed on 06 July 2024).
Kanjwal MA,  Ghaferi AA. Biomedical Applications of Electrospun Graphene Oxide. Encyclopedia. Available at: https://encyclopedia.pub/entry/35496. Accessed July 06, 2024.
Kanjwal, Muzafar A., Amal Al Ghaferi. "Biomedical Applications of Electrospun Graphene Oxide" Encyclopedia, https://encyclopedia.pub/entry/35496 (accessed July 06, 2024).
Kanjwal, M.A., & Ghaferi, A.A. (2022, November 21). Biomedical Applications of Electrospun Graphene Oxide. In Encyclopedia. https://encyclopedia.pub/entry/35496
Kanjwal, Muzafar A. and Amal Al Ghaferi. "Biomedical Applications of Electrospun Graphene Oxide." Encyclopedia. Web. 21 November, 2022.
Biomedical Applications of Electrospun Graphene Oxide
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This entry is adapted from the peer-reviewed paper 10.3390/s22228661

Graphene is an allotrope of carbon and is made up of sp2-bonded carbon atoms placed in a two-dimensional honeycomb lattice. Graphite consists of stacked layers of graphene. Due to the distinctive structural features as well as excellent physico-chemical and electrical conductivity, graphene allows remarkable improvement in the performance of electrospun nanofibers (NFs), which results in the enhancement of promising applications in NF-based sensor and biomedical technologies. 

electrospinning electrospun nanofibers graphene graphene oxide electrochemical biosensors

1. Introduction

Graphene is undoubtedly one of the most outstanding carbon-based nanomaterials [1], and displays an atomic layered sheet composed of sp2-bonded carbon atoms, which can be produced by a top-down approach (e.g., mechanical, electrochemical, or chemical exfoliation of graphite) or by a bottom-up approach (e.g., chemical vapor deposition and chemical synthesis) [2][3][4]. In relation with other carbon allotropes, graphite, fullerenes, and carbon nanotubes, graphene presents numerous unique chemical and physical features. Due to its honeycomb lattice structure having two carbon atoms per unit cell, a linear dispersion of the energy spectrum exists, because of the close association of the valence and conduction bands and the Brillouin zone corners [5]. Consequently, charge carriers in graphene act as no-mass relativistic particles or Dirac fermions. Additionally, a powerful ambipolar electric field effect together with quick movement of charge carriers was noticed [6]. Due to the delocalization of the out-of-plane π bonds originating from the sp2 hybridization carbon atoms, a remarkable carrier mobility of ~200,000 cm2 V−1 s−1 has been realized for suspended graphene [7][8] and ~500,000 cm2 V−1 s−1 for a graphene established field effect transistor (FET) [9][10][11][12]. One more significant electronic feature of graphene is the exceptional fractional quantum Hall effect for charge carriers at room temperature [5][13]. Furthermore, monolayer graphene is extremely transparent when the visible light is incident on it (~2.3% absorption) [14]. Graphene has an excellent mechanical property, having a Young’s modulus of ~1.1 TPa [15]. Additionally, graphene is highly thermally conductive, revealing a thermal conductivity of ~5000 Wm K−1 and great surface area (2630 m2 g−1) [11][12]. Due to these distinctive chemical and physical characteristics and the distinctive biocompatibility, graphene has gained substantial attention in industry as well as scientific circles for several promising applications such as biosensors, biotechnology [16][17], clinical diagnosis [18], antibiotics and antivirals [19][20][21][22][23][24], targeted and photothermal therapy [25][26][27][28], drug distribution [29][30][31], and electric stimulants [32].
The group members of graphene-based nanomaterials (GNMs) consist of single and multilayer graphene, graphene oxide (GO), reduced graphene oxide (RGO), graphene oxide quantum dots (GOQDs), and graphene quantum dots (GQDs) [33][34][35]. Every group member of GNMs possesses distinct physico-chemical characteristics, that include surface chemistry, structure, composition, electrical conductivity, and mechanical strength, that are essential for a large number of operations [36][37][38][39]. Hence, GNM-based materials have a promising prospect and offer great new possibilities, not only in the energy sector [40][41][42][43], electronics [44], and environmental applications [45][46][47][48], but also in various biomedical operations, which include biosensors, noninvasive processes such as bioimaging, gene transfer therapy, drug delivery, regenerative medicine, and stem cells [49][50].
In the recent past, nanocomposites consisting of nanomaterials and polymer matrices have captured substantial interest in the area of contemporary materials science because of their outstanding thermal and chemical properties, electrical conductivity, and mechanical characteristics that can be realized at comparably less filler loading [51]. The increased performance is mostly assigned to extraordinary aspect ratio (100–1000 nm) fillers, which result in low-mass nanocomposites with tunable and diversified features which render them promising applicants for various new and exciting applications such as disease diagnosis and tissue regeneration [52][53], promoting cell proliferation [52], and identification of microorganisms and present unprecedented methods for biosensing applications. Specifically, nanocomposites consisting of GNM-based materials with polymeric materials or nanoparticles, such as metals, nanoscale hollow tubes composed of carbon atoms (CNTs), and graphene quantum dots, can perform a significant part in producing novel biosensors and promoting biomedical applications with improved efficiency [51][54][55].

2. Biomedical Prospects of GO

GO is a monolayer material and chemically composed of carbon, oxygen, and hydrogen [56]. GO is an oxidized type of graphene and is composed of several carbonyl (RCOR), carboxyl (RCOOH), hydroxyl (ROH), and epoxy functional groups [57][58]. GO is a hydrophilic material in essence and can easily form stable aqueous colloidal suspensions, that enable the development of macroscopic structures with economical operability [57][59]. GO possesses several surface defects and the core material exhibits substantial similarities to pure graphene [60]. GO is a very promising material in the biomedical field due to its favorable chemical structure. GO has important applications in smart drug/gene delivery because of its exceptional surface area [61]. The nanosheet structure of GO can safeguard biomaterials from deterioration, increase the chemical bonding between biomolecules and the core parent chain, and also enhance their distribution time [61][62]. The oxygen-rich nature, hydrophilicity, and superflexibility of GO permit excellent cell growth and expansion in biomedical engineering [63][64]. Moreover, due to striking features such as antibacterial and antimicrobial properties and drug delivery ability, GO is a very promising applicant for wound healing applications [65]. The development of new blood vessels by GO is found to be dose-dependent and is well documented [66]. GO and reduced graphene oxide (rGO) can enhance the number of reactive oxygen species (ROS) (ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen) in organisms, thus promoting formation of new blood vessels [66]. GO, due to its innocuous nature and biocompatibility, has great potential in medical instruments [67][68][69]. However, it is also well documented that concentrations of GO above a certain optimum level may result in a reduction of biocompatibility [70][71]. The ROS generated from GO induce oxidative stress when antioxidant levels are low, such as caspase 3-mediated apoptosis (caspases are crucial mediators of programmed cell death) under the influence of adrenal pheochromocytoma PC12 cells [72][73][74]. Therefore, it is essential to combine GO with other suitable and established biomaterials to ensure increased biocompatibility. One method to achieve this is by employing electrospinning technology. It is possible to electrospin GO and different biopolymers to form GO-loaded electrospun nanofibrous composites [74]. The selected polymer should be biocompatible, biodegradable, and harmless in nature.

3. Electrospinning in Tissue Engineering

Electrospinning technology plays an important role and is a fascinating approach for tissue engineering. Electrospinning technology contributes significantly to forming nanoscale or microscale fibrous structures possessing interjoined pores, which mimic the extracellular matrix (ECM) in living tissue [75]. This phenomenon is supported by observing the distinguished characteristics of skin as well as bones. Skin and bones are composed of extremely interconnected porous structures that are exploited in cell migration, a fundamental process in the development and continuation of multicellular organisms, and nutrient transport, important in transporting nutrients and chemical signals to the tissues and eliminating waste materials and heat [75][76][77]. The compact nanofibrous structures of electrospun scaffolds have significant and tuned porosity. The porosity decreases as the electrospun fiber diameter decreases from the micrometer to nanometer level, due to more close and compact packing. This phenomenon causes inferior cellular movement and generates a two-dimensional surface instead of the regular three-dimensional structure surrounding the ECM [78]. To date, electrospun nanofibrous matrices have been extensively explored in tissue engineering areas such as osseous tissue, muscle cells, chondrocytes, skin cells, neurons, and angiogenesis [75][79][80][81][82][83][84][85][86][87][88][89]. The addition of GO into the polymer matrix can change the physico-chemical properties of an electrospun nanofibrous scaffold utilized in tissue engineering. Oxygen-rich GO has hydrophilic features and, due to the relationship between GO and the electrospun nanofibrous matrices, the modified platform may exhibit increased hydrophilicity, cell growth, mesenchymal stem cell (MSC) osteogenic differentiation, mechanical strength, and biological activity, all essential parameters in tissue engineering [90]. GO has important applications in osteoregeneration with excellent outcomes [91], in which GO increases the stem cells located in the bone that play an important role in bone repair and growth [92]. This process is accomplished by Coulomb interactions and hydrophobic interactions with the proteins of the immediate small-scale environment of a plant cell or tissue [92].
Bone regeneration is one of the most common applications for electrospun GO nanofibrous matrices in tissue engineering based on the latest literature survey. The incorporation of GO enhanced the hydrophilicity of the electrospun nanofibrous matrices [93][94][95]. Biocompatibility of the electrospun nanofibrous matrices was shown to be unchanged in comparison with MG63 cells [96] but it was enhanced in different investigations utilizing human osteosarcoma cells (HOS), [97] MG-63 cells [98], bone marrow multipotent stem cells, medicinal signaling cells, or mesenchymal stem cells (BMSCs) [94], and C2C12 myoblast cells [99]. Cellular adhesion and proliferation were increased with the incorporation of GO in electrospun nanofibrous matrices [90][94][95][96][98][100][101][102][103][104]. Osteogenic expression and differentiation were significantly enhanced [94][97][98][105][106] in addition to mineral accumulation [100][102][103]. The enzymatic response time was increased, with respect to basic phosphatase [103][107]. The incorporation of GO in electrospun nanofibrous matrices enhanced mechanical properties significantly [96][97][98][100][102][103]. In one report, the elongation at break was enhanced by 462% and tensile strength increased by around 230%. The incorporation of GO in calcium phosphate and polyvinylpyrrolidone has found good application in biomedical implants [108]. These electrospun composite matrices exhibited excellent biocompatibility characteristics as was evident when MG-63 human osteoblast-like cells were added to calcium phosphate-polyvinylpyrrolidone/GO 5 wt % composites. Cell attachment and live/dead investigation exhibited no detrimental effects of the composite matrices [108].
This indicates that the above-mentioned material could be a potential applicant as scaffolding in osteoregeneration for biomedical engineering operations. In one report, poly (3-hydroxybutyrate-co-4-hydroxybutyrate/graphene oxide) (P34HB/GO) was used for osteoregeneration in laboratory rats with critical size congenital calvarial bone defects [109]. After testing, P34HB and P34HB with 1 mg/mL GO were analyzed for osteoregeneration. With two months of exposure, 47.2% and 60.77% fresh bone regeneration was seen in the P34HB and P34HB/GO groups, approximately [109]. These outcomes indicate the existence of GO in electrospun nanofibrous matrices and its positive impact on osteoregeneration and stimulation of bone formation by GO [109]. These electrospun nanofibrous matrices loaded with GO could be regarded as a medicinal alternative in tissue engineering, because of their porosity, biomechanics, osteoregeneration ability, and low-cost production process [109]. Another research team reported the utilization of electrospun silk fibroin scaffolds through the modification of GO with bone morphogenetic protein-2 (BMP-2) polypeptide for an enhanced osteoregeneration study [94]. NFs loaded with GO have been used in tissue engineering of muscle with diverse outcomes. PCL-GO nanofibrous composites have exhibited excellent biocompatibility for myoblast (C212) differentiation and have promising prospects in future-generation muscle tissue regeneration [99]. Nevertheless, these nanofibrous composites are also known for decreasing cell elongation by differentiation for randomly oriented and smooth fibers in CS12 cells [70] and therefore should be precisely evaluated when employing these scaffolds for tissue engineering of muscles [70]. Polyurethane (PU)/poly(ethylene oxide) (PEO)/GO electrospun nanofibrous matrices have exhibited degeneration of the scaffold, the absence of inflammation, and penetration of cells in vivo within the confines of the scaffold. PU/PEO/GO composite biomaterial has excellent biodegradability and biocompatibility and tuned porosity to perform as an appropriate material for regeneration of soft tissue in human beings [110]. Similarly, PU/PCL/GO electrospun nanofibrous composites exhibited reasonable compatibility with dermal fibroblasts, and the inclusion of GO enhanced the hydrophilicity of the polymeric matrices [111]. Electrospun poly(vinyl alcohol)/reduced graphene (PG) has been investigated for its promising prospects in engineering dermal tissue. Moreover, glucose-reduced graphene oxide (GRGO) was produced by using glucose as a reducing agent [112]. NFs were crosslinked by using acidic glutaraldehyde in a dimethyl ketone. PG nanofibrous matrices exhibited outstanding compatibility in the presence of CCD-986Sk (human fibroblast cell line), and significantly increased the metabolism after cell culture for three weeks compared to control groups, in the absence of GRGO [112]. The incorporation of GO into a PVA matrix resulted in a minor shifting from hydrophilicity to hydrophobicity. However, in general, the PG nanofibrous matrices enhanced fibroblast cell growth and feasibility, exhibiting promising prospects of PG for dermal tissue engineering operations. Electrospun PCL/gelatin/GO nanofibrous composites exhibited great antibacterial qualities towards Gram-positive and Gram-negative bacterial strains. The nanofibrous composites may be employed as a scaffold of reasonable electrical conductivity in nerve regeneration, with drug release characteristics [64]. Drug release characteristics demonstrated pi stacking among TCH drug and GO and, therefore, enhanced the controlled delivery of TCH in relation to comparison groups in the absence of GO. Electrospun polycarbonate urethane (PCU)/GO nanofibrous matrices have been investigated in nerve regeneration applications [113]. Neural outgrowth of pheochromocytoma (PC 12) as a model cell line showed better results in the presence of the PCU/GO nanofibrous matrices compared to poly-L-lysine (PLL) material. Even though the mean diameter of neurites was identical in both GO- and PLL-coated surfaces, the neurites were elongated in the case of GO-coated matrices [113]. This work displays a unique surface engineering technology for GO coating on nanofibrous polymeric matrices. This unique platform could be employed as a 3D neuronic scaffold that can encourage neuroregeneration by providing better extracellular matrix surroundings [113]. Silk has been blended with GO to achieve an electrospinning technique and fabricate nanofibrous matrices for designing excitable nervous tissue, due to their ability to be electrically excited, which, subsequently, results in the production of action potentials [114]. Electrical conductivities were enhanced from approximately 4 × 10−5 S cm−1 in the dry state to 3 × 10−4 S cm−1 following the hydration process. Cellular adhesion and viabilities were found to be fine when these polymeric matrices were analyzed in the presence of neurinoma NG108-15 neuroblastoma cells. Progress in cell proliferation and metabolism was noticed for the GO-containing nanofibrous matrices, and subsequently increased more in the electroactive polymer composite of silk/rGO (demonstrating a modification in configurations when stimulated by an external electric field) [114]. Moreover, these electroactive polymeric matrices are promising candidates to enhance the nerve cellular response and can work as supporting material for nerve tissue regeneration applications.

4. Drug and Gene Delivery

Due to the excellent surface to volume ratio and stability, GO is extensively utilized in drug delivery systems and has promising prospects as a nanocarrier  [115][116][117][118]. GO has demonstrated excellent biocompatibility and ion exchange characteristics, due to which GO is an exceptional applicant for drug delivery applications [116][119]. GO is known to load aromatic drugs with great productiveness by basic noncovalent interactions. The quinone part of aromatic drugs experiences pi stacking interactions due to the π conjugated system of GO, yielding hydrophobic characteristics [120]. The carboxyl and hydroxyl functional groups of GO permit powerful hydrogen bonding to occur, connecting the nanocomposites and aromatic drugs under study [120][121][122]. Oxygen-rich GO can be efficiently modified for addition of biomolecules, e.g., vitamin B9, which encourages and enhances drug loading capacity [123][124]. Integrating GO with polymers through electrospinning can have a positive impact and advantages in drug delivery operations. The solubility issues of hydrophobic drugs can be addressed by the use of appropriate polymers [125]. Defense against detrimental factors, such as environmental deterioration and disintegration, is provided by the use of suitable polymers [125]. A broad spectrum of polymers are used in NFs incorporating GO for drug delivery systems [113][116][120][125][126]. These drug-oriented polymers assist in developing the drug loading ability and increasing the delivery performance of the system. For example, poly (acrylic acid) (PAA) polymer has been reported to successfully transport and release ampicillin and cefepime drugs [127]. Similarly, poly(ε-caprolactone) (PCL) has been described as a transporting agent for dexamethasone and simvastatin drug delivery [116].
The mixture of polyvinylpyrrolidone (PVP) and PCL has been successfully involved in controlled delivery of vancomycin hydrochloride drug [113]. Zein, a versatile protein biopolymer, has been reported in precise delivery of tetracycline hydrochloride (TCH) and ketoprofen (KET) to treat infections caused by bacteria, such as pneumonia, other respiratory tract infections, and chronic wound [112][115]. Similarly, polymers such as poly(lactic) acid (PLA) have been investigated for their drug release properties, and biopolymers that include PEI and PLGA have been efficiently utilized for stable and transient transfection and immobilizing somatomedin C hormone [119][120].
Quick/slow biphasic drug delivery systems have been investigated for quick release of a specific amount of drug for instant improvement of a patient’s condition, followed by sustained release, to escape periodic administration [128][129][130]. It has been reported that web thickness of the nanofibrous matrices has regulated drug delivery [129], alternatively, GO concentration controlled the drug release profile [130]. In general, GO incorporation has a positive impact on cumulative drug release and drug delivery rate was enhanced [131]. GO has also been consistently employed in electrospun nanofibrous matrices for antibacterial applications. rGO embedded polymeric nanofiber mats have been used for “on-demand” photothermally triggered antibiotic release of the antibacterial agents ampicillin and cefepime, which exhibited enhanced drug release, in relation to drug delivery at ambient temperature [125]. Both Gram-positive and Gram-negative bacterial strains were effectively suppressed by antibiotic drug delivery. An antibacterial wound dressing incorporating GO has exhibited extended drug release of tetracycline hydrochloride (TCH) [132]. Outstanding antibacterial characteristics were observed, and subsequently resulted in rapid wound healing [132]. It is well documented that GO concentrations up to 1% enhanced fibroblast cell growth and cell attachment [132]. Anti-inflammatory drugs, such as corticosteroids, and cholesterol have been included in the GO drug delivery process. Dexamethasone and Zocor medications have been utilized to enhance the number of osteoblasts, which arise from the osteogenic differentiation of MSCs [133]. Electrospun nanofibrous composites loaded with GO are promising candidates in neural cell treatment. The stimulation of autophagy in intracellular signal transduction pathways by methylene blue caused neural progenitor cell (NPC) proliferation on the electrospun nanofibrous composite to remain in the G0 phase [134]. NPCs were protected from programmed cell death, and tau phosphorylation proteins were reduced due to the influence of electrospun nanofibrous composites [134]. An innovative drug delivery method composed of polyvinyl alcohol and gum tragacanth blended with tetracycline accommodating GO and TCH has been reported for administration of active ingredients in transdermal operations [135]. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay exhibited that the synthesized polyvinyl alcohol/gum tragacanth/graphene oxide or PVA/GT/GO/TCH composite NFs possess excellent cell growth when investigated in a usual endothelial cell line (HUVECs) [135]. This composite exhibited excellent antibacterial properties compared to control groups lacking GO or TCH. These excellent features are due to the existence of GO in electrospun nanofibrous composites and facilitated the controlled drug delivery and enhanced antibacterial characteristics [135]. Therefore, it is suggested that this composite material can be a potential applicant in precise and controlled drug delivery systems. Like drug delivery systems, gene delivery has been encouraged by the use of GO in electrospun nanofibrous composites. Genetic material (DNA) has been administered in stem cells to enhance transfection effectiveness and function as a medium for stem cell development and cell differentiation in biomedical engineering applications [136]. Similarly, somatomedin C has been delivered in electrospun GO/PGLA composites to increase neural stem cell (neurons, astrocytes, and oligodendrocytes) growth, differentiation, and continuation [137]. This electrospun composite approach exhibited exciting features for the development of the neuroprotective consequences of introduced nerves [137].

5. Cancer Therapy

NFs containing GO and loaded with drugs have been investigated for their potential uses in cancer treatment. A polyethylene oxide/chitosan/graphene oxide (PEO/CS/GO) electrospun nanofibrous composite has been investigated for the controlled release of the chemotherapy drug doxorubicin (DOX) or adriamycin [138]. Drug loading of around 98% was achieved and the better prolonged controlled release was because of pi stacking relationships between GO and DOX in the loaded PEO/CS/GO electrospun nanofibrous composite [138]. Further investigations revealed the drug delivery dependence on different pH values. For instance, the fast drug release at pH 5.3 can be assigned to the chemical bonding between GO and the DOX drug, leading to an uncertainty in the presence of acidic surroundings. Cell viability investigations revealed that using human lung epithelial carcinoma (A549) has encouraging results when electrospun nanofibrous composites are utilized rather than free DOX in drug delivery studies. This would avert the damaging negative impact and effects of free DOX [138]. Moreover, more research was carried out on DOX drug delivery utilizing chitosan/poly(lactic acid)/graphene oxide/TiO2 (CS/PLA/GO/TiO2) electrospun nanofibrous composites to study the effect on human lung epithelial carcinoma (A549) [139]. First, sustained delivery of the DOX drug was observed and, subsequently, some uncontrolled release was observed when utilizing electrospun composites with 30–50 μm nanofiber diameters after 14 days of incubation time [139]. At pH 5.3, faster drug release of DOX was observed compared to pH 7.4, indicating a pH dependency as a result of a slight association between chemotherapy DOX drug and electrospun nanofibrous composites [138]. The existence of a magnetic field enhanced the prohibition of cell proliferation of the electrospun nanofibrous composites on human lung epithelial carcinoma cells [139].
It is well documented that adhesion features of biopolymers corresponding to cancer cells are associated with the control of the spreading of stage IV (4) cancer [140]. An association remains between biomaterials and the restriction of disease development [140]. In this regard, poly(caprolactone) (a biodegradable, biocompatible material)-based electrospun nanofibrous composite combined with GO results in the formation of PCLMF-GO nanofibrous composites and was reported for disease development restriction [141]. The covalent functionalization of GO and nitrogen plasma functionalization were employed for surface modification and to regulate physical and chemical characteristics of the electrospun nanofibrous composite to simultaneously encapsulate and eliminate the primary human dermal fibroblast adult cell line (HDFa) and human adenocarcinoma cells (MCF-7) [141]. Incorporation of GO has a positive impact and increased cell growth and attachment and directed cancer-associated fibroblast (CAF) encapsulation. Distinct photothermal therapy of the encapsulated cancer cells was significant and was feasible by high near-infrared absorbance (NIR) of GO [141]. This electrospun nanofibrous composite has a positive impact on the therapeutic effect of metastatic cancer cells and consequently decreased tumor distress and metastasis eruption in vivo. This electrospun nanofibrous composite also helps in prompt diagnosis of cancer cells in advance by employing an in vivo noninvasive fluorescent imaging technique [141]. An in vitro tumor prototype has been designed and developed based on graphene nanocomposites. In one study, GO was added to acetylated cellulose to compose nanocomposites for in vitro cell cancer examinations [142]. A human breast cancer cell line (MCF-7) was incorporated in the nanocomposite, and exhibited that cell development on these composites had a positive influence on cell viability, cell attachment, and proliferation in relation with those developed on basic CA [142]. Incorporation of GO also increased the mechanical strength of the nanocomposites. These outcomes suggest that GO performed an integral part in the human breast cancer cell study [142].

6. Wound Healing

Advancement and progress in nanotechnology and biomedical engineering introduce unique polymeric materials for wound healing and wound dressings. NFs have gained great interest for wound dressing and wound healing operations, due to their easier processing techniques. In general, electrospun fibers are on micrometer to nanometer scale and have a large surface to volume ratio, tunable porousness, and controlled morphology, that are all important parameters for drug loading and release [143][144][145][146]. Epithelialization (an essential component of wound healing) can be achieved, due to the close resemblance of the nanofibrous structure to extracellular matrix, and this encourages quick wound healing [147]. The proper selection of materials for the electrospinning technique is essential, and natural or synthetic polymers or their combination must be compatible with characteristics of the scaffold. Biopolymers are obtained from natural sources and are biocompatible, biodegradable, and harmless. Glycans, such as chitosan (a linear polysaccharide) and cellulose (structural polysaccharide), and proteins that include collagen (structural protein) and silk have been extensively used in electrospinning technology for drug release and wound dressing operations [148][149]. Most of these biopolymers have striking characteristics that facilitate wound healing. For instance, chitosan is an impressive antimicrobial agent because of its cationic properties [148].
There are multiple synthetic polymers being employed in wound dressing and healing, such as PVA, PLA, PEO, PVP, and PCL [150][151][152][153]. Generally, the mechanical strength of synthetic polymers is much better than natural polymers or biopolymers. These human-made polymers are efficiently dissolved in a broad spectrum of solvents, that facilitates the smooth functioning of the electrospinning technique [150]. In addition to excellent mechanical strength and hydrophilicity of GO, they also exhibit better antibacterial characteristics, due to the infiltration of the plasma membrane and the generation of very reactive oxygen radicals and the fact that GO is highly electrically conducting [154]. The blending of GO with suitable polymers employing the electrospinning technique can increase cell growth [155][156]. The electrospun nanofibrous matrices containing GO hold the moist air encircling the wound and speed up the healing process [53]. It is well documented that when GO is used, greater than optimum concentrations may have toxic effects and could have negative impacts and results in electrospun nanofibrous scaffolds used in wound dressing and healing applications [157]. Therefore, it is imperative to blend GO with suitable polymers having antimicrobial activity and biocompatibility to generate potent wound dressing and healing materials. The electrospun nanofibrous matrices containing GO have significant antibacterial and antimicrobial properties. These nanofibrous matrices have been generated with a range of polymers [158][159][160][161][162][163][164][165][166][167]. When GO is included in these electrospun nanofibrous matrices, Gram-positive and Gram-negative bacteria are killed [168].
The antimicrobial and antibacterial properties of electrospun nanofibrous matrices could be enhanced by the incorporation of antibiotic and antimicrobial drugs. Ciprofloxacin (Cip) and ciprofloxacin hydrochloride (CipHcl) are antibiotics that have been successfully integrated into electrospun GO nanofibrous matrices [164]. The nanofibrous architecture, the presence of GO within the NFs, and the nanofiber separation are essential for the drug incorporation and drug delivery. These electrospun nanofibrous matrices were highly effective at targeting and eliminating Gram-negative E. coli, Staphylococcus aureus, and Gram-positive B. subtilis [164]. The delivery profile of these electrospun nanofibrous matrices escaped the much anticipated “burst release”, and the extended delivery of two drugs takes place [164]. Cerium dioxide (CeO2) and peppermint oil (PM) incorporated electrospun GO nanofibrous matrices have also been investigated for their antibacterial characteristics [53]. It was reported that these composites showed much better antibacterial properties, because of the presence of the surface charge of cerium dioxide. The CeO2-PM oil-PEO/GO incorporated electrospun nanofibrous matrices were found to be less damaging to connective mouse tissue (L929) cells in relation to electrospun nanofibrous matrices composed of only cerium oxide and peppermint oil [53] and enhanced re-epithelization in wound healing [53][169]. Similarly, a wide range of drugs that include ibuprofen, ketoprofen, and vancomycin have been investigated and incorporated in a PCL/GO electrospun nanofibrous matrix for antimicrobial characteristics [169]. These electrospun nanofibrous composites used near-infrared light (NIR) for drug delivery for more than 72 h [169]. Similarly, allicin (the natural component of garlic) has been successfully incorporated into NFs composed of chitosan, PVA, and GO [170]. Furthermore, it was reported that the amount of GO in the electrospun nanofibrous matrices played an important role in controlled drug release of allicin. GO containing electrospun nanofibrous matrices acted as an excellent prolonged bacteriostatic agent, in which the dimension of the bacteriostatic circle referring to the GO electrospun nanofibrous matrices does not shrink considerably in comparison to S. aureus [170]. Cytotoxicity investigation revealed that the collected electrospun nanofibrous matrices enhanced viability in relation to the L929 fibroblast cell line in the absence of GO. The inclusion of allicin did not suppress the cellular proliferation.
The electrospun nanofibrous matrices’ viability was reduced to marginally lower than 80% once GO was included, which implies that electrospun nanofibrous matrices carrying allicin as well as GO do not have any cytotoxic effect and can encourage cellular viability, because cellular viability above 70% is usually regarded as harmless in comparison to the biological materials under investigation [170]. The addition of allicin and GO as low as 0.1% into the electrospun nanofibrous matrices enhanced the cell–matrix adhesions or FAs and increased cellular growth [170]. Further studies showed that this material is a promising candidate and has good hydrophilic nature and reasonable water-holding capacity (WHC). The moist surface is helpful and facilitates wound healing [170]. The blending of GO and silver nanoparticles (AgNPs) was investigated for their antimicrobial properties [171]. A co-reduction method was employed to adhere AgNPs on the surface of the rGO.
Fabricated rGO-Ag was then uniformly distributed in PCL matrix and then subjected to an electrospinning technique to form smooth electrospun nanofibrous matrices. The incorporation of rGO-Ag increased the specific conductance, decreased the fiber diameter, and increased the mechanical properties [171].
Antibacterial properties of these electrospun nanofibrous matrices were around 99.55% and 99.46%, when tested on Staphylococcus aureus and Escherichia coli O157:H7, therefore rendering these nanofibrous matrices as appropriate material in wound healing applications [171]. Biocompatibility effects on human skin fibroblast cells [169][172], L929 cells (can be used in the development of novel anti-cancer treatments) [53][65], and MC3T3-E1 osteoprogenitor cells are well documented [161]. The fibroblast cells are of main interest due to their importance in wound healing applications [173]. It has been reported that electrospun nanofibrous matrices containing GO were innocuous to NIH/3 T3 fibroblast cells [173], enhanced cell growth of normal human dermal fibroblasts (NHDFs) [160], and encouraged cell attachment and activity of human dermal fibroblast cells (HDFs) [169]. A cytotoxic effect was observed when concentrations of GO of more than 1% were used [173], and this finding reveals that the fabricated nanomaterial should be blended with quercetin to enhance the electrospun nanofibrous matrices’ antibacterial properties [173]. The compatibility of a material with blood has also been reported when using GO-containing electrospun nanofibrous matrices, composed of PVA/GO [166] and collagen/carboxylated graphene [167]. The degradation investigations revealed that the gelatin/ZnO/GO electrospun nanofibrous matrices entirely degraded in a week, exhibiting well-controlled degradation properties [174]. At the same time, a separate study revealed that the impact of GO extended the degradation in simulated biological fluid (SBF), that indicates that electrospun nanofibrous matrices may be stable for extended duration in vivo tests [175]. The utilization of GO in electrospun nanofibrous matrices can be precisely controlled to expedite or decelerate the degradation rate and this is determined by the required applications [174][175]. Electrospun nanofibrous matrices containing GO are promising candidates for in vivo wound healing applications. Research on rat models has exhibited that electrospun nanofibrous matrices containing GO assisted in the regeneration of a substantial dermal injury, performing as a short-term dermal graft, two weeks after a post-operative procedure. The 1.5% GO concentration lead to compact and healthy skin regeneration, with wound healing of more than 99% recovery three weeks after a post-operative procedure [163]. One research team reported the re-epithelialization of wounds after two weeks in a rat model, in the presence of 1% GO in PVA/collagen/GO [165], and GO/Ag/arginine nanofibrous matrices [65]. Another study showed that electrospun nanofibrous matrices composed of PVA/GO had a significantly positive impact on wound healing and more than 90% efficiency was achieved at a 0.25% concentration of GO in rat models [166]. The incorporation of GO into electrospun nanofibrous matrices has increased mechanical properties significantly [65][160][166][167], and improved many physical and chemical properties [65][160][172] as reported by many research teams. Decisively, electrospun nanofibrous matrices containing GO have a broad range of applications. Characteristics that include antimicrobial properties, drug loading and drug delivery, tissue compatibility, hemocompatibility, re-epithelization, and outstanding mechanical features render these exciting materials very promising candidates for wound healing functions [168][169][172].

7. Biomaterials/Medical Equipment

Polymeric biomaterials have found tremendous importance in medical devices [176]. Surface modification of these medical devices is highly desirable to enrich biocompatibility and tissue–implant relationships [177]. Electrospun nanofibrous matrices are promising candidates and can be employed as biomaterials and medical equipment. Electrospinning technology can be used to produce sub-micron diameter fiber scaffolding and utilized as artificial blood vessels/channels and coronary artery stents [178]. It has also tremendous importance in engineering electrically conductive cardiac patches [179][180]. These electrospun nanofibrous matrices can be designed in a way to utilize the exciting biological and mechanical features of the medical equipment [181]. Electrospun nanofibrous matrices encourage cellular intrusion and consequently lead to the deposition of ECM. This is because electrospun nanofibrous matrices perform as an ECM counterpart for distinct body cells, stem cells, and cancer cells to promote biomedical engineering, and aid in cellular proliferation, cellular specialization, and assembly modeling of cancer cells [182]. The incorporation of GO into nanofibrous matrices for use in medical equipment and specific biological materials can increase its hydrophilic nature, because of the presence of oxygen-rich functional groups on the material under study [183][184]. It is also well documented that incorporation of GO into electrospun polymeric material improves mechanical properties, including tensile strength, malleability, and specific conductance [166][179][185]. The addition of GO in small optimum concentrations in fields that include biomedical engineering, drug release, and wound dressing and healing is innocuous and may encourage cellular adhesion and cellular growth [90][102][110][129][130][132][161][163][165][175][178][186]. It is also well documented that incorporation of GO over particular optimum concentrations can lead to toxic effects, decreased cell activity, and production of free radicals [173]. Therefore, it is imperative to investigate the proper biomaterials and optimum GO concentration for a wide range of materials and their use in medical equipment. Electrospun nanofibrous matrices containing GO have been engineered and applied in electroactive cardiac patches. These engineered materials are appropriate as their electrical conductivity can be regulated to an extent that matches the natural cardiac electrical activity [179]. These features of this exciting material containing GO help in unfolding of fabric configurations in cardiomyocytes and human umbilical vein endothelial cells where the GO is close to the surface of the nanofibrous matrices [179]. Moreover, it has been found that electroactive cardiac patches containing GO play an essential secondary role as delivery vehicles for pharmaceuticals and biological molecules, and it was observed that heparin (an anticoagulant and used in preventing or in treatment of certain blood vessel, heart, and lung conditions) was effectively assimilated for the adsorption of bovine serum albumin [180]. This finding is outstanding because the functionalization of the nanofibrous matrices with heparin advances the biocompatibility of the medical equipment. Electrospun nanofibrous tubular grafts containing GO (0.5%) exhibited biological compatibility to cells derived from the endothelium of veins from the umbilical cord and mouse embryonic fibroblasts (3T3). These electrospun nanofibrous tubular grafts exhibited biocompatibility with artificial blood vessels concerning burst pressure and suture retention strength (the suture retention strength of synthetic vascular grafts is an important mechanical characteristic that affects the functioning of the vascular grafts). Moreover, it was shown that platelet attachment and human endothelial cell adhesion on the interior surface of the electrospun nanofibrous tubular graft were lower, thus exhibiting promising prospects in vascular tissue engineering [178]. In addition, electrospun nanofibrous matrices containing GO have been examined as a vascular stent coating [187]. The surface functionalization of the electrospun nanofibrous matrix with nitrogen-doped reduced graphene oxide (NrGO) generated an anion, which resulted in repelling of low-density lipoproteins (LDLs), also known as “bad” cholesterol, regarded as the fundamental reason for arteriosclerosis or atherosclerotic cardiovascular disease [187]. Similarly, the fabrication of GO/polycarbonate urethane (PU) films for implantable medical equipment was investigated [177]. The GO/PU films exhibited antibacterial properties for both Gram-positive and Gram-negative bacterial strains and continued low platelet adhesion (essential function in response to vascular injury) and biocompatibility in relation to mouse fibroblast L929 cells, thus rendering GO/PU films as promising material for the coating of cardiac implantable electronic devices [177]. The inclusion of GO increased the mechanical properties of the polyethylene terephthalate/GO electroconductive cardiac patch significantly. This material possesses the systematic and mechanical stability to establish electromagnetic coupling (EM) at myocardial infarction sites to maintain normal heart functioning [180] and enable diagnostics [188].
Recent investigations have revealed that NFs containing GO can be used for applications in the electric power industry and sensing platforms. It has been shown that NFs containing GO can be used to fabricate a triboelectric nanogenerator (TENG) (new energy technology for converting human kinetic and ambient mechanical energy into electrical energy and works on the principle of Maxwell displacement current) [189]. The NFs containing GO were highly effective in the generation of electrical energy after submersion in phosphate buffer solution for four weeks. This device, called a nanogenerator, was employed to use electric energy to stimulate pheochromocytoma (PC12) cell lines, resulting in increased cellular adhesion and cellular growth [189]. More studies in future are required to evolve this platform as an environmentally friendly and economical technology for biomedical operations [189]. Influenced by this, an environmentally friendly, electrospun nanofibrous triboelectric nanogenerator composed of GO/PCL NFs and cellulose paper was investigated and turned out to be promising in biomedical engineering [189]. This material containing 4 wt% GO content showed good electrochemical properties. The nanofibrous structure had a positive impact on charge density accumulation [189]. The electrospun nanofibrous triboelectric nanogenerator composed of PCL loaded with 4 wt% GO with a dimension of 4 × 4 cm2 showed an increase up to 98% in relation to electromotive force (emf) or open-circuit voltage [189]. More than twenty LEDs were regularly operated by the triboelectric nanogenerator (TENG) configuration, by simple personal touch. The anionic charge from oxygen-rich GO and the nanopores from the electrospun nanofibrous matrices are the principal reason for this excellent performance [189]. Moreover, reports propose that, because of its harmless constituents, this GO-containing material could be regarded as a green energy producer, and address concerns of electric scraps in relation to self-driven medical instruments [189]. Electrospun nanofibrous matrices containing GO can generate a connection and improved 3D conductive network due to the better interaction of NFs with one another and have significant importance in motion sensing applications [190]. Extraordinary electronic properties, ductility, stability, and sensitiveness render this GO-loaded material composition a promising applicant in human motion sensing. The wide extent of motion sensing that includes normal human activities such as walking, hopping, finger and muscle movements, speaking, sneezing, etc. indicates that GO-loaded NFs are promising candidates as an advanced wearable gadget and may have substantial importance in health/fitness tracking applications [190]. State-of-the-art research has investigated the use of NFs containing GO in biosensing platforms. For this purpose, GO/PVA electrospun nanofiber scaffolds have been reported. The copper (Cu) nanoflower has been developed and fabricated and has important application as a glucose biosensor based on electrochemical measurements [188]. The modified gold chip displayed a lower limit of quantification of 0.018 μM for glucose. These findings suggest that this material system can be a promising candidate in electroanalysis of glucose in biological fluid for mobile testing and rapid diagnostics.
Quantum chemical modeling established on the density functional theory (DFT) can be applied to investigate the interface characteristics of graphene surfaces. The utilization of DFT-established quantum chemical models to characterize the graphene surface provides numerous benefits, such as the capability to investigate the surface at the atomic level. Contemporary analytical techniques, which include high-resolution transition electron microscopy and scanning tunneling microscopy, can be utilized to investigate the graphene surface at the molecular level. However, these techniques are expensive and have certain limitations. Consequently, quantum chemical modeling is needed to investigate the surface on an atomic level. In addition to atomic-scale investigation, conceptual DFT-established quantum chemical models (Fukui functions and dual descriptors are extremely useful in realizing electron transfer (ET) reactions and yield important input into surface energy levels. Fukui functions are chemical descriptors that are beneficial to analyze the reactivity of systems toward electron transfer.

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Subjects: Materials Science, Composites
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Muzafar A. Kanjwal
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Amal Al Ghaferi
View Times: 447
Revisions: 2 times (View History)
Update Date: 22 Nov 2022
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