INTRODUCTION:

Electrospinning is a technique of making fibres that are capable of being used for many biomedical purposes. It’s called electrospinning as the process of making these fibres involves the using of electric force to attract the charged threads of polymer solutions to convert them into fibres of required diameter, mostly ranging to a few hundreds of nanometre. These fibres again could be solid or hollow depending upon the requirement. Nanofibers that are produced via electrospinning can be controlled critically during its composition which provides controlled mechanical properties and structure. Certain aspects of the process such as binding and proliferation of the cells and loading of the drug are positively affected by the large ratio that exists between the surface and the volume the electrospun nanofibers. This method is comparatively cheaper, easier to work with, good reproducibility if the ambient parameters are maintained, and is suitable for various formulations.^1,2

The word “electrospinning” arises from the ancient word “electrostatic spinning”.

A revival of interest in the process was noticed which may be credited to nanotechnology, as extremely fine fibres of several polymers having their diameters in the nanometre range can be rather easily constructed using this particular technique.⁵

In the present article, an attempt was made to summarize the in-depth detailed about the electrospun nanofibers, its process of manufacturing, critical process parameters affecting the process and its advanced applications.

Process of electrospinning:

The process takes place briefly in the following steps

· Accumulation of repulsive charge:

Firstly, there must be an accumulation of enough repulsive charge and this accumulated repulsive charge must be exactly same as the surface tension.

· Taylor cone formation:

The accumulation of repulsive charges leads to drop surface on the conducting tube and the formed drop surface initiates forming a cone which is generally mentioned as “Taylor cone”. This happens only if the field angle acting on the conducting polymer solution or polymer melt is 49.3º leading to the formation of an equilibrium cone.

· Formation of Nanofibers:

To make a liquid jet that arises at Taylor Cone, the repulsive force must overcome the surface tension which happens when the field charge is increased beyond 49.3º. While performing this process there should be an ambient amount of Cohesive attraction between the molecules, otherwise, the jets formed undergo fragmentation, and these formed fragments get sprayed onto a collector plate rather than forming fibres.

Once the fibres start forming at the Taylor Cone, they reach towards the collector plate while travelling through the air which helps in evaporation of the solution leaving with solid fibres that get deposited on the collector plates by keeping the distance between the fibre origination point to the collector plate as long as it assists in solvent evaporation due to the extended time the jet spends in the air.^3,4 The fibres resulting from the above process have diameters that qualify as nanofibers.⁶

PARAMETERS AFFECTING: ELECTROSPINNING:

Identification of critical process parameters (CPP) which have an impact on the reproducibility of nanofibers is a decisive step in understanding and controlling the manufacturing procedure of electrospinning. These critical processing parameters can be broadly classified into three types which further classified into several types.

A. Critical Parameters affecting the Process of Electrospinning:

1. Applied Voltage:

Electric charge is governed by the applied voltage and it affects the formation of fibres and it determine fibre size and bead formation.^3,4 The polymeric solution is exposed to an external electric field and high voltage that is inducing the needed charges initiating the process. This happens as the electrostatic force successfully the surface tension.^7,8 Increasing the applied voltage is advised but only up to a critical value^6,9 which varies from polymer to polymer.¹⁰ It is observed that finer fibres are obtained in the presence of larger voltage as the polymeric solution stretches in association with the charge repulsion in the polymer jet. Inversely when the voltage shoots past the critical value there is a decrease in the Tylor Cone size and at the same time there is an increase in the jet velocity while having a constant flow rate eventually causing the expansion of the fibre diameter along with bead formation⁶

2. Flow rate:

As we use polymer solution to wind fibres, flow rate of the solution plays a strong part and is believed to influence the porosity, size and shape of resulting fibres.^3,4 It has been observed that every polymeric solution has a critical point at which it forms uniform nanofibers. Flow rate behaves in the same manner as the applied voltage as the flow rate above a critical value will produce be fibres having a larger diameter and larger pore size and have greater chances of having a beaded structure which is attributed to the unsatisfactory drying of the jet.^6,11 The reason why nether flow rate is advisable is as it offers sufficient time for the solvent to evaporate which otherwise would encourage the formation of web-like structures as a result of fibres fusing together⁷. To sum up, lower flow rate generates the formation of the desired thinner fibres and high flow rates above the critical value leads to fibres with larger diameters.⁶

3. Capillary–Collector Distance:

Interspace between the capillary is one of the critical parameters where the fibres emerge and the collector where the formed fibres are collected is believed to impact both size and morphology of the fibers formed. The recommended capillary-collector distance would be around 10 to 20cm for most of the conventional electrospinning process.^3,12 Decreasing this distance gives the fibres less time which as we have seen before allows less evaporation of the solvent leaving us with fibres having larger diameters and having beaded structures.⁶ In a few cases changing the capillary-collector distance had no major impact on the diameter of the fibres but they were observed to have beaded structures when the distance was reduced immensely.⁷

B. Solution Related Parameters for Electrospinning:

1. The concentration of Solution:

This influence stretching of the charged polymeric jet. When polymeric solutions were used at relatively lower concentrations, the surface tension, as well as the electric field, used to lead the fragmentation of the fibres before they could be arriving at the collector.¹⁰ These fragmented polymer chains exhibit electrospraying instead of the expected electrospinning the fibres.^6,13 And comparatively higher polymeric concentrations will cause the viscosity to increase, which further entangles the polymer chains.

It’s not recommended to go beyond the critical value of solution concentration as that would interrupt flow through the tip of the needle¹⁰ causing droplet at the tip to dry out and eventually blocking the polymer jet initiation.^6,13

2. Solution Viscosity:

The viscosity of polymer-solvent combination governs the smoothness and continuity of the fibre. As it is evident that low viscosity fails to form the fibres and ends up forming particles, while dense viscosity demands a higher electric field though it makes it hard to operate but still giving us bead free fibres.^3,14,15 However, it has been noted that increasing the polymeric concentration causes a rise in the polymer viscosity and as seen before polymeric solutions with high viscosity interrupt the flow and at tip of the metallic needle the droplet will dry out.¹⁰

3. Molecular weight:

This guides the viscosity of polymeric solution which further impacts the morphology of those fibres.^3,16 Generally, increasing the molecular weight, till it reaches its critical value should lead to a rise in the solution viscosity and the fibres formed should have lesser to no beads. Generally, high molecular weight polymers are advised as they engage in substantial entanglement of the chain, helping the fibre formation during the process of spinning. Whereas, polymer solutions having molecular weight towards the lower side may generate beaded fibres or may form droplets.⁶

4. Surface Tension of The Solution:

It is one of the critical parameters which is basically the extent of cohesive forces that exist among the molecules. It relies on the polymer as well as the solvent used and on the solution composition.³ There is balance between the electric field ( concentration, conductivity, and the viscosity) and the surface tension, which is believed to have an impact on the final morphology.^6,17 The effect of solvent on the nanofiber development with polyvinyl pyrrolidone and inferred that coupling weaker surface tension with stronger viscosity gives smooth nanofibers with ethanol.^3,18

5. Solution Conductivity:

It is vital, especially in formation of the Taylor and in controlling size of the nanofibers. Solutions having good conductivity will provide the necessary charge on the face of the droplet that is required for the formation of Tylor cone. This will also help in attaining fibres with a smaller diameter. It has come under observation that there may occur obstruction in the Taylor cone formation if the conductivity of solution rises above a critical value which is believed to be caused due to the Coulombic forces that exist across the external electric field and charges on the surface of the fluid.^6,9,10,17 Compared to the less conductive solution, a solution with stronger conductivity encounters a stronger tensile force, hence making it preferable for electrospinning.^3,13

6. Solvent Volatility:

The interspace between the collector and the capillary tip is of just a few centimetres and the route taken to arrive at the collector by jet is a few folds more than that. The porosity and the time a fibre would take to dry depending upon the solvent used to solubilize the polymer^3,19 The polymers chosen commonly are entirely soluble in the solution taken and have boiling point that is moderate compared to the temperatures that the process might use which affects the solvent volatility. Solvents that are volatile can be used in the process as they help to increase the evaporation rate and easily evaporate from tip of the needle. Solvents that have high rate of volatility are not used as they do not allow the complete formation of the fibres. Conclusively, the rate of evaporation and their volatility profile are valuable parameters.^6,9,10

C. Environment Related Parameters for Electrospinning:

1. Relative Humidity (RH):

The relative humidity can be said to be a detail for the formation of nanofibers that are ultrafine and have acceptable morphology. RH has an influence on the pore formation on surface of fibres via evaporation of solvent or else by supervising the solidification of the jet. The chemical specification of the polymer in use decides the appropriate amount of the RH required. A high RH represses the rate of evaporation if the surface area of polymeric jet rises and charge per unit area on jet surface goes downwards causing capillary instability and the formation of beaded structures.^6,9,20

2. Temperature:

Temperature affects the formation of nanofibers that are ultrafine in size having qualified morphology. The average diameter size of the nanofibers gets altered according to the temperature used. It does so by encouraging two opposite effects; firstly, by expanding the solvent evaporation rate and secondly, by lowering the viscosity of solution. They act out as opposite mechanisms, but both eventually lead to a decrease in mean fibre diameter. Hence concluding that a rise in the temperature is observed to form finer nanofibers.^6,9,10

APPLICATION OF ELECTROSPUN: NANOFIBRES:

Biomedical Applications Electrospun nanofibers are being used extensively for biomedical application in recent times. This could be dedicated to the size that is in submicron range and the surface area along with the highly porous nature of the composition and closeness to the biostructures that the fibres have to offer that are produced using the mechanism of electrospinning. Furthermore, this technique offers flexibility to engender individualized structures with needed surface and bulk properties.¹³

1. Wound Healing:

Getting hurt and having wounds is an extremely common scenario. Healing of the wound refers to regenerating of the damaged dermal and epidermal tissues²¹ recovering from injuries takes a set of complex biochemical actions including homeostasis, inflammation, proliferation and remodelling.^10,22,23 As it is possible to tailor these properties using electrospinning, electrospun wound dressings are more advantageous over other wound dressings²¹. Electrospinning as a process is capable of fabricating cosmetic masks which has its application in cleansing and healing of the skin. The large surface area of skin mask that has been electrospun allows the flow to and fro from skin. Additionally, these masks can also be easily used without being hurtful.¹⁰ Electrospun polyurethane membrane offers effective fluid exudation from the wound without causing a build-up under the membrane. The water loss that usually occurs due to evaporation occurs in a controlled fashion, has excellent oxygen permeability and inhibits the environmental microorganisms from contaminating the covered area. Biocidal silver iodine complex was added to fibres in order to avoid bacterial invasion.²⁴ Polyvinylpyrrolidone iodine complex released the active iodine slowly and gradually. Owing to iodine’s broad-spectrum microbicidal activity, electrospun PVP-iodine containing nanofibers can have external antibacterial, anti-mycotic and antiviral uses. Silver ion is a strong biocidal agent as it works on sixteen types of bacterial strains²⁵ When silver nitrate is added into the polymer solution being used it gives us nanofiber having long-term biocidal properties and the release of the silver ions happens in a controlled manner. A silver/PVA nanofiber membrane showed tremendous biocidal activity and was stable in an environment having moisture, as well as a stable release profile.^21,26

2. Drug Delivery:

In targeted drug delivery, the drug is given to the specific tissue and the amount of the medication that reaches to the other tissues is decreased to an impressive extent. This results in the drug being localized on targeted site and the drug performs to its maximum efficacy.²⁷ Electrospun nanofibers are capable of achieving targeted drug delivery as dissolution rate tends to go up with the increase in the surface area of the carrier and the drug itself making digestion and absorption of drugs easier.^10,28 the high voltage that is the part of the electrospinning process has no effect on the activity of the drug being used, hence making drug loading an easy and safe process using this method. The nanofibers generally have the high specific surface area and the length of their diffusion passage is short which gives them a higher release rate. Depending upon the needs, the release profile can be closely controlled by supervising the characteristics of the nanofibers. There is a broad range of polymers that can be used such as PLC, PLA, and PLGA which are biodegradable in nature that are used to encapsulate antibiotics and antibacterial agents and PVA and PEG which are of hydrophilic nature that are primarily used to control the release pattern.^3,21,29 Owning to the flexibility of electrospinning technique like its ability to release a drug in a controlled and sustained manner at the target site just by modifying the drug-release kinetics, it is looked as a reassuring method for drug delivery¹⁰. The reason why controlled release is stressed upon is because minimizes the toxicity and side effects and it also improves convenience as they are mostly²¹ administered via oral, tropical and implantable routes making it an efficient way of delivering drugs for medical therapy.³ A study in which tetracycline hydrochloride with poly PEVA, PLA and their 50:50 blend was used for treating periodontal disease and the reports showed a 5 days release profile with PEVA and the blend, indicating that it was capable of being applied to controlled-release technology.³⁰

3. Tissue Engineering:

Tissue engineering is a process where cells, suitable biochemical and physicochemical factors engineering principles all work in synergy to form new tissue that is viable and mimics the natural biological tissue eventually to be used for a medical condition that may require repair, replacement, maintenance or enhancement of the function of that particular tissue or organ. Scaffolds that are fabricated using electrospinning technique are biocompatible and biodegradable. They have the ability to create the indigene environment of the target cells by mocking their extracellular matrix.¹⁰

3.1 Blood vessels:

Blood vessels play the role of transport conduit system and play a vital role in important processes like organ development, morphogenesis of the tissues, barrier formation and in the wound healing process. They are a fundamental part of the skeletal system and participate in maintaining bone homeostasis³¹. They are composed of various types of cells. The innermost layer is endothelial cells, followed their outer, abluminal surface by perivascular cells³². There are several kinds of blood vessels and they all differ in size, mechanical property, biochemical nature, cellar content and structural organization. Due to such complexity in structures, developing blood vessel of fine diameter (diameter<6 mm) is difficult. A bilayered electrospun nanofiber made up of an outer layer of a stiff and oriented polylactic acid and an inner layer of pliable and randomly oriented PCL was fabricated to imitate the natural mechanical and morphological features of the blood vessel. On testing, it was seen that this bilayer structured scaffold supported attachment, spreading and the growth of mouse fibroblasts and human myofibroblasts and it matched with the mechanical properties of reference vessels and it eventually empowered the integration and growth of the cells. There was a study conducted in which nanofibers made up of different polymers such as polyglycolic acid, collagen and gelatin were tested in vivo in rat vastus lateralis muscle. The results showed that nanofibers made up of “collagen rapidly and densely got infiltrated by interstitial and endothelial cells. There was the genesis of functional blood vessels within 7 days. On the other hand, nanofibers made up of while gelatine, as well as synthetic nanofiber, were not infiltrated to an impressive extent and induced fibrosis.”^21,33,34

3.2 Bones:

Bone grafting is used in clinical setups to amplify bone repair and regeneration. In an in vivo experiment in which mesenchymal stem cells cultured PCL construct was implanted in the omental of rats, it was observed that after 30 days the constructs were able to maintain the mechanical specifications of the original scaffolds and there was an appearance of a bone-like structure transplantations have a lot of drawbacks ³⁵. Hence, bone tissue engineering using nanofibers made of PCL are being studied extensively. There was another similar experiment in which nanofibers from gelatine/PCL blend and PCL mixture with calcium salt nanoparticles and hydroxyapatite (HAp) nanoparticles was used. The gelatine/PCL blend showed enhanced mechanical strength and surface wettability which aid in better cell clamping and growth on the used scaffold.^10,36

3.3 Muscles:

The first nanofiber to be tested for its ability to culture a muscle was collagen and it was specifically tested for smooth muscles. The results of the test showed that there was some degree of cell proliferation and the cells were merged into the collagen nanofibers after one week of seeding. In addition, there was an enhancement in the elasticity and tensile strength of the fibres leading to improved cell adhesion. Argon, plasma-treated PS nanofibers showed enhanced wettability which resulted in two-fold increase cell adhesion²¹

Electrospun nanofibers constructed from polyester urethane (DegraPol®) (commercial product) was employed on three different skeletal muscle cell lines: murine myoblast cell line, rat myoblast cell line (L6) and primary human satellite cells (HSCs). These showed positive adherence and proliferation.²¹

3.4 Skin:

A it is the outermost part of our bodies and is the largest tissue, it acts as a barrier from external intrusion and regulates heat and water retention. A wide range of polymers (SF, collagen, gelatine, chitosan, hyaluronic acid) and synthetic polymers including PLGA, PCL has been used to construct nanofiber mats and have been tested for their cytocompatibility to keratinocytes and fibroblast.

Nanofibers constructed of polymer blends show acceptable attachment and proliferation of the cells. Increased hydrophilicity was seen when a small amount of polyethylene glycol of low molecular weight was blended with PLLA resulting in the enhanced biological activity of the fibroblasts. It was seen that the presence of two types of a hydrophilic nanofiber like chitosan and PVA fibre wettability of the nanofibers was increased. This, in turn, amplified the nutrient uptake while performing cell culture and encouraged fibroblast migration, its multiplication and penetration into the fibre.

There was a study done on a three-dimensional silk matrix made up of firoin nanofibers that was constructed by depositing the freshly electro spun silk fibroin nanofibers in a solution of methanol. The constructed 3D matrix showed cell multiplication inside of fibre.²¹

3.5 Neural Tissues:

Nanofibers that have been made by electrospinning are potential substances for repairing the neurological tissues which are for obvious reasons a very delicate task to perform. In an In vitro study done on neural stem cells using PLLA nanofiber scaffold showed that it was supportive of neural stem cells differentiation and neurite outgrowth. As well as provided good adhesion of the cells. This study was taken further by aligning the PLLA nanofiber which revealed that the directions in which NSC elongated and the fact that the outgrowth was analogue to the direction of fibre alignment. When these fibres were aligned in this way, they serve by providing topographical guidance.

Incorporating electrical stimulation during cell growth improves cell function. This was proved by a study in which Polypyrrole was grown on PLGA nanofibers, and the resulting nanofibers showed 40-50% longer neuritis and 40-90% more neurite formation in comparison to those devoid of electrical incitement. In another study conducted with 11 rats, 5 of which showed positive nerve regrowth at the end of 30 days of implanting PLGA nanofiber guidance. Nerve stem cell adherence, differentiation, on the PLGA nanofiber mats were seen²¹

4. Enzyme Immobilization:

In order to simplify a reaction process, to maintain good catalysis activity and to enhance the stability as well, a catalyst carrier is a must. As electrospun nanofibers have a larger surface area they can be employed as catalyst carriers to enhance the catalytic ability as they offer many active sites. Nanofibers have high porosity and the pores are impressively interconnected which aids a continuous flow of chemical reactions and biological processes eventually enhancing the interactions between the catalyst and the reactant²¹

To functionally ease the resistance to diffusion of the matrix and to amplify the ability to catalyse, the highly specific surface area and porous character of the electrospun fibres can be used. Largely, surface loading method is the method for enzyme immobilization in electrospun fibres. With diameters of 100 to 150 nm, an experiment where a-amylase was immobilized by surface covalent bonding to electrospun polyvinyl alcohol/ polyacrylic acid nanofibers. The free amylase was less resistant than immobilized a-amylase. The enhancement in the activity and stability even at an elevated temperature and a broader pH range is due to keratinolytic protease immobilized on the PVA nanofibers. The covalent immobilization of amylase and protease onto electrospun poly (styrene-co maleic anhydride) nanofibers with limited retention of their catalytic activity by incubating electrospinning fibre mat in the protein solution.

The catalytic activity of amylase was preserved when co immobilized with protease. The PVA/Zn2+ polymer/ionic metal composite nanofiber was fabricated and it worked as a carrier in lipase immobilization. The nanofibers that are not capable of dissolving in water were dissolved with lipase solution which gave lipase immobilized nanofibers. This nanofiber was seen to have better enzymatic stability. These mobilized nanofibers could keep 90 percent activity at 70 degree Celsius after 40 minutes elapsed, while the other form lipase stopped performing after 40 minutes.³⁷

CONCLUSION:

This review article summarized the in-depth detail about electrospinning nanofibers its manufacturing process and the detail about the critical process parameters (CPP) involve in the electrospinning process. The electrospinning nanofibers and its advanced applications in the field of biomedical sciences and its advances. This article also providing the detail about the use of electrospinning nanofibers in drug delivery with special emphasis on nano-sized drug delivery system specifically for low solubility drug molecules. The article also summarizes the application of nanofibers in tissue engineering. Bone repair and regeneration in muscle culture, in skin structuring, repairing nerve tissue, and enzyme immobilization.

Despite all research being done by a scientist in the field of electrospinning Nanofibers the more evaluation in terms of biomedical sciences and drug delivery to be required which can successfully deliver the more efficient alternative to traditional drug delivery systems.

REFERENCES:

1. Karakas H. Electrospinning of Nanofibers and Their Applications. Istanbul Tech Univ Text Technol Des Fac. 2015;(August):1–35.

2. Huang ZM, Zhang YZ, Kotaki M, Ramakrishna S. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos Sci Technol. 2003;63(15):2223–53.

3. Bhattarai RS, Bachu RD, Boddu SHS, Bhaduri S. Biomedical applications of electrospun nanofibers: Drug and nanoparticle delivery. Pharmaceutics. 2019;11(1).

4. Nayak R, Padhye R, Kyratzis IL, Truong YB, Arnold L. Recent advances in nanofibSre fabrication techniques. Text Res J. 2012;82(2):129–47.

5. Yu D-G, Zhu L-M, White K, Branford-White C. Electrospun nanofiber-based drug delivery systems. Health (Irvine Calif). 2009;01(02):67–75.

6. Vlachou M, Siamidi A KS. Electrospinning and drug delivery. Available from: https://www.intechopen.com/books/advanced-biometric-technologies/liveness-detection-in-biometrics

7. Bera B. Literature Review on Electrospinning Process (A Fascinating Fiber Fabrication Technique). Imp J Interdiscip Res (IJIR. 201;2(8):972–84.

8. Wang X, Kim YG, Drew C, Ku BC, Kumar J, Samuelson LA. Electrostatic Assembly of Conjugated Polymer Thin Layers on Electrospun Nanofibrous Membranes for Biosensors. Nano Lett. 2004;4(2):331–4.

9. Akhgari A, Shakib Z, Sanati S. A review on electrospun nanofibers for oral drug delivery. Nanomedicine J. 2017;4(4):197–207.

10. Haider A, Haider S, Kang IK. A comprehensive review summarizing the effect of electrospinning parameters and potential applications of nanofibers in biomedical and biotechnology. Arab J Chem. 2018;11(8):1165–88.

11. Singh S. World Journal of Pharmaceutical Research. Age (Omaha). 2015;20(8):60yrs.

12. Bhardwaj N, Kundu SC. Electrospinning: A fascinating fiber fabrication technique. Biotechnol Adv. 2010;28(3):325–47.

13. Pillay V, Dott C, Choonara YE, Tyagi C, Tomar L, Kumar P, et al. A review of the effect of processing variables on the fabrication of electrospun nanofibers for drug delivery applications. J Nanomater. 2012;2013(1)-1-22

14. Sukigara S, Gandhi M, Ayutsede J, Micklus M, Ko F. Regeneration of Bombyx mori silk by electrospinning - Part 1: Processing parameters and geometric properties. Polymer (Guildf). 2003;44(19):5721–7.

15. Baumgarten PK. Electrostatic spinning of acrylic microfibers. J Colloid Interface Sci. 1971;36(1):71–9.

16. Koski A, Yim K, Shivkumar S. Effect of molecular weight on fibrous PVA produced by electrospinning. Mater Lett. 2004;58(3–4):493–7.

17. Lin Weng JX. Smart Electrospun Nanofibers for Controlled Drug Release: Recent Advances and New Perspectives. 2017;371(14):1280–3.

18. Yang Q, Zhenyu LI, Hong Y, Zhao Y, Qiu S, Wang CE, et al. Influence of solvents on the formation of ultrathin uniform poly (vinyl pyrrolidone) nanofibers with electrospinning. J Polym Sci Part B Polym Phys. 2004;42(20):3721–6.

19. Megelski S, Stephens JS, Bruce Chase D, Rabolt JF. Micro- and nanostructured surface morphology on electrospun polymer fibers. Macromolecules. 2002;35(22):8456–66.

20. Valencia Jacobs, Rajesh D. Anandjiwala MM. The Influence of Electrospinning Parameters on the Structural Morphology and Diameter of Electrospun Nanofibers. J Appl Polym Sci. 2010;116(5):2658–67.

21. Fang J, Niu HT, Lin T, Wang XG. Applications of electrospun nanofibers. Chinese Sci Bull. 2008;53(15):2265–86.

22. Gao Y, Truong YB, Zhu Y, Louis Kyratzis I. Electrospun antibacterial nanofibers: Production, activity, and in vivo applications. J Appl Polym Sci. 2014;131(18):9041–53.

23. Daniel J Smith, Darrell H Reneker, Albert T McManus, Heidi L Schreuder-GIbson, Charlene Mello MSS. Electrospun Fibers and an apparatus therefor. Vol. US00675345. 2004.

24. Khil MS, Cha D Il, Kim HY, Kim IS, Bhattarai N. Electrospun Nanofibrous Polyurethane Membrane as Wound Dressing. J Biomed Mater Res - Part B Appl Biomater. 2003;67(2):675–9.

25. Spadaro JA, Berger TJ, Barranco SD, Chapin SE, Becker RO. Antibacterial effects of silver electrodes with weak direct current. Antimicrob Agents Chemother. 1974;6(5):637–42.

26. Jeong EH, Yang J, Youk JH. Preparation of polyurethane cationomer nanofiber mats for use in antimicrobial nanofilter applications. Mater Lett. 2007;61(18):3991–4.

27. Rani K, Paliwal S. A Review on Targeted Drug Delivery: its Entire Focus on Advanced Therapeutics and Diagnostics. Sch J Appl Med Sci. 2014;2(1):328–31.

28. Chen Z, Mo X, Qing F. Electrospinning of collagen-chitosan complex. Mater Lett. 2007;61(16):3490–4.

29. Ji Y, Ghosh K, Li B, Sokolov JC, Clark RAF, Rafailovich MH. Dual-syringe reactive electrospinning of cross-linked hyaluronic acid hydrogel nanofibers for tissue engineering applications. Macromol Biosci. 2006;6(10):811–7.

30. Kenawy ER, Bowlin GL, Mansfield K, Layman J, Simpson DG, Sanders EH, et al. Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly (lactic acid), and a blend. J Control Release. 2002;81(1–2):57–64.

31. Ramasamy SK. Structure and Functions of Blood Vessels and Vascular Niches in Bone. Stem Cells Int. 2017;2017(Figure 1).

32. Sivaraj KK, Adams RH. Blood vessel formation and function in bone. Dev. 2016;143(15):2706–15.

33. Vaz CM, van Tuijl S, Bouten CVC, Baaijens FPT. Design of scaffolds for blood vessel tissue engineering using a multi-layering electrospinning technique. Acta Biomater. 2005;1(5):575–82.

34. Telemeco TA, Ayres C, Bowlin GL, Wnek GE, Boland ED, Cohen N, et al. Regulation of cellular infiltration into tissue engineering scaffolds composed of submicron diameter fibrils produced by electrospinning. Acta Biomater. 2005;1(4):377–85.

35. Amini AR, Laurencin CT, Nukavarapu SP. Bone tissue engineering: Recent advances and challenges. Crit Rev Biomed Eng. 2012;40(5):363–408.

36. Wong HM, Chu PK, Leung FKL, Cheung KMC, Luk KDK, Yeung KWK. Engineered polycaprolactone-magnesium hybrid biodegradable porous scaffold for bone tissue engineering. Prog Nat Sci Mater Int. 2014;24(5):561–7.

37. Sun Y, Cheng S, Lu W, Wang Y, Zhang P, Yao Q. Electrospun fibers and their application in drug controlled release, biological dressings, tissue repair, and enzyme immobilization. RSC Adv. 2019;9(44):25712–29.

Received on 14.03.2020 Modified on 11.04.2020

Research J. Pharm. and Tech. 2020; 13(11):5569-5575.

DOI: 10.5958/0974-360X.2020.00972.5