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Nanofibers for skin regeneration.

Introduction

Scientific evaluations of major complications and potentially serious damage in the skin are wound infections. Wound surfaces are sterile immediately following thermal injury. However, colonization with autogenous germs or through contact with the infected, generally take place in 48 hours [1, 2]. Estimates show that about 70% of patients with severe burns, death due to infection, despite the considerable efforts of the medical staff and advanced medical care [3].

Moreover, in certain diseases such as diabetes with chronic non-healing wounds or venous ulcers, stimulated the regeneration of tissue may cause important implications for patients. Therefore, efforts to invention of new treatments and more efficient so far have been less satisfactory and desirable [4].

Under the extraordinary effects of electrospun nanofibers in skin care and wound healing, and a few studies in this unique area, this review article focuses on the capabilities of polymer nanofibers in the regeneration of the skin. This article is divided into several sections; and discusses the suggestions and data from recent research and studies. So, our goal is to evaluate the most recent studies, over the past ten years, towards skin regeneration by nanofibrous scaffolds.

Electrospinning

Electrospinning (Fig. 1) is a common procedure for preparing thin (micro or nano meters) of fibers from a liquid. At first, Formhals registered the new process for creating polymer nanofibers in his laboratory using electrostatic power. In subsequent years, the scientists followed Formhals research [5-9]. In electrospinning simplest situation consists of a syringe containing the polymer solution, two electrodes with a DC voltage that its high negative charge attached to the syringe tip and the positive charge connected to the collector. By applying a high voltage area, conductive polymer solution is drawn to the collector and the fibers are formed. Of course, various external and internal factors affect the formation and size of the fibers. The external factors include the type of polymer and solvent, flow rate, electric field, the distance between the tip of the syringe and the collector plate, etc. While internal factors influence the morphology of the fibers, but the solution intrinsic factors, particularly surface tension of the solution, have a boarder role. Relevant surface tension and viscosity of the polymers solution is the essential reason for the unique formation of nanofibers [8]. The conductivity of the solution and the polymer molecular weight are factors that affect on jet uniform elongation and fiber generation [10].

[FIGURE 1 OMITTED]

Nanofibers

Generally nanofibers are called the fibers with a size less than 1000 nm [11, 12]. Perfect features, such as high ratio of surface volume, high porosity and permeability are due attention. Nanofibers are made of different materials such as polymers, composites and ceramics with various applications in the biomedical field [13-15] (Fig.2), space science, textiles, drug delivery [16], the industry filtration [17], environment [18], energy [19] and sensors [20]. But many patents on the topic, the medical field is a key component of studies at the request nanofibers. Nanofibers are still expected to be used in various fields of medical, for example, to make scaffolds for the growth and proliferation of stem cells, tissues regeneration, filtering and advanced wound dressing, and so on.

Another important consideration in relation to the nanofibers is the methods of fabrication. There are several ways to make nanofibers, such as drawing, template synthesis, phase separation, self-assembly and electrospinning, etc. The advantages of the phase separation process and self-assembly technique are simple tools to formation of nanofibers with unique ultra-fine diameter, respectively [21]. But perhaps the most common way to produce nanofibers is the electrospinning technique (also known as electrostatic spinning) [22-24].

[FIGURE 2 OMITTED]

Skin

The skin or integument (cutis) is the largest organ essential to life with a weight of about six pounds, 8% of body mass, and the body area of about 1.2 to 2.2 [m.sup.2] and the barrier between inside and outside of the body with total thickness of about 1.5 to 4.0 mm [25]. The skin showed a promising opportunity to renew and repair. Anatomic (Fig. 3), the skin consist of three layers: epidermis, dermis and hypodermis. The skin is constantly exposed to harsh environmental conditions such as chemical, thermal damage, osmotic or mechanical, and is the first barrier against microbial invasion. Relevant friction properties assist locomotion and manipulation, are some of the common tasks of the skin. The skin is capable of absorption and excretion, even selectivity permeable to certain chemicals. It is a soft tissue and resistance to external shear stresses. Damage the skin categorizes different levels. The slight damage occur when the surface layer of the skin, the epidermal layer, destroys, and reepithelialization and skin graft does not. [26]

Skin graft was done in India about 2,000 years ago. But in fact, did not develop until the 19 century. But during the past 200 years by increasing the possibilities, skin graft surgery has become one of the major surgeries for the purposes of health and beauty. But before explaining new researches in skin graft is needed to understand the anatomy of the skin, which is described in next section.

[FIGURE 3 OMITTED]

Skin layers

Epidermis

Epidermis, keratinized epithelium surface, is the outermost layer of skin composed of leaves, such as keratinocytes epithelial cells. Its thickness changes in the eyelids almost 0.1 mm to about one mm in the palm of the hands and feet [27]. Epidermis is renewed approximately every 3 to 4 weeks. The outer skin cells form keratin after the death, an insoluble fiber protein that protects the body against pathogens and keeps the body fluids.

Dermis

Dermis gives strength to the skin. change the thickness of about 0.3 mm in the eyelids to nearly 3 mm in the palm and soles [28]. Dermis has two layers, the papillary and reticular. Papillary located directly below the epidermis and contains fibroblast cells, produce collagen types as the main component of connective tissue. Reticular layer found between the papillary layer and produce collagen and flexible fibers. Dermis also contains hair roots, blood and lymph vessels, nerves, sweat and sebaceous glands. Dermis is often known as real skin.

Hypodermis

Hypodermis or subcutaneous fat layer, the innermost layer of the skin is mainly fat, which lies between the muscles, bones and the top layer of skin. This layer addresses the unique shape of the body and the insulation. Hypodermis and its fat content have a major role in maintaining body temperature.

Regeneration of the skin

The skin regeneration process form the outer layer of skin, which consists of 15-20 layers of keratinocytes (mostly keratin), embedded in a matrix of the skin lipids. With human aging, the regeneration process becomes less efficient and wrinkles and other signs of aging appear.

With a deep wound in the skin, the epidermis to the dermis expands wounded, bleeding occurs and the inflammatory reaction begins. The mechanisms of blood clotting are activated shortly, and a clot of crust is formed in a few hours. The crust temporarily restores the integrity of the epidermis and reduces the ingress of microorganisms. After the crust is formed, the basal cells begin dividing by mitosis and migrate to the edges of the scab. After a week the edges of the wound is pulled together by contraction. With the continued migration of epithelial cells around the scab, the skin is restored by the activated stem cells. These activated cells produce collagen fibers and ground substance. The blood vessels will grow rapidly in the dermis, to restore the circulation.

But in a serious injury, when the migration of epithelial cells and the contraction of the tissue may not cover the wound, the seams along the edges of the damaged skin or even the replacement of lost skin graft may be necessary to restore the skin.

Skin graft is a surgical procedure that damaged skin or non-healing wounds are replaced by new skin or skin substitutes.

In serious injury, repair mechanisms are unable to restore skin to its original state. The repaired area consists of abnormally numerous collagen fibers and relatively few blood vessels. Damaged the sweat and sebaceous glands, hair follicles, muscle cells and nerves are rarely repaired. Usually they are replaced by fibrous tissue and the result is the formation of a rigid, fibrous scar tissue. In such cases, the skin tissue engineering using nanofibers would work fine. Regarding to the high costs and pain in autologous skin graft, the use of nanofibers as artificial skin will be very efficient.

There are some techniques that can be used in the skin grafts process. One of the most common techniques is autograft that the skin grafts from one area of the body and transplant to another. Allografts involving the skin grafts from a donor to a patient. xenograft is the procedure that the tissue is derived from another species and transplanted to a patient for skin grafting. As previously mentioned using nanofibers as artificial skin take place in the xenograft category.

Nanofibers for skin care

Considerable efforts have been met for that imitated human skin substitutes generated in the last 25 years [29]. Nanofibers, as a candidate for the effective restoration of the skin are potentially promising. Application of nanofibers as scaffolds for the regeneration of the skin, is schematically illustrated (Fig.4). Typically in research, are first, keratinocytes and fibroblasts isolated from human donor tissue, and then expanded in vitro before seeding on the right fibrous scaffold. For a full-thickness skin is the same, the fibroblasts and the mat, first used to determine portion of the skin and then the keratinocytes are seeded on top of the dermis to form the last part epidermal of the epidermal skin. Based on the results of research projects, the future of the nanofiber mats used in the biomedical field is optimistic. over the past decade, many types of polymers, synthetic or natural, were used as recovery or skin wound healing agent in biomedical researches [30, 31].

[FIGURE 4 OMITTED]

In addition to the nature of polymers, natural or synthetic, some of the most important properties of nanofiber scaffolds are biocompatibility, biodegradability and the diameter of nanofibers [32].

Although the use of synthetic polymers in the fabrication of nanofibers is much easier than natural polymers, but despite the abundance of biopolymers, high cost of purification, can be a big problem. So, with regard to the remarkable properties of natural polymers, such as biocompatibility and biodegradability, mixing synthetic and natural polymers are versatile procedure [33].

Skin injuries and solutions

The skin, the main barrier of defense against foreign intrusion caused, exposed to severe destructive agents such as wounds, lesions, physical and chemical causes. Almost every day it hurts caused negligible mechanical injury. They can easily be attended by plaster when they are not too large. Mechanically induced ulcers have different essence and can be defined as: cuts, puncture wounds, bruises, lacerations, abrasions, bites and burns.

Damaged skin, large or small, is more sensitive to harsh cases such as bacterial or microbial agents, and dehydration, so faster regeneration of skin is essential. In fact, the recovery is not simply the renewal of skin cells and is the complex process of assembly and adhesion, as many cells and tissues form the skin regenerated. Meanwhile, the infection prevention and reduction of inflammation both are points noteworthy for the renewal of the skin.

Wound healing has three undercurrents during inflammation, tissue formation, and the phases of tissue remodeling. This is a complex process involves series of events with clotting, inflammation, granulation tissue formation, epithelialization, neovascularization, collagen synthesis and wound contraction [34]. These events overlap in time, and represent a diverse set of cytokines secreted by platelets, macrophages, fibroblasts and epidermal cells [35, 36].

In short, today, treatment protocols are often complicated skin surgeries. These methods replace the damaged skin, instead of healing the skin, are also expensive and inconvenient. Therefore, the use of alternative procedures to skin graft from both natural and synthetic biomaterials has been considered. Although alternative methods such as artificial skin, unable to create a perfect model as the normal skin [37], but research studies are being conducted around the world to find better results.

Nanofibers as Cellular Scaffold

One of the main applications of nanofibers mat in the biomedical field is the scaffolding [38]. In fact, cellular scaffolds are an alternative way instead of conventional transplants. Living tissue cells are arranged in the extracellular matrix (ECM) with close links. The ECM is a network of organic molecules adheres to each of the curious animal cells and tissues and made of fibrous proteins such as collagen and proteoglycans. Meanwhile, the transduction of chemical signals in the ECM is its vital role in living tissues.

Indeed, the main purpose of the use of nanofibers in the skin management is imitation of the extracellular matrix. Several parameters affect the nanofibers functions, such as the type of fiber diameter and porosity, biodegradability and biocompatibility of the polymer that have large effects on cell adhesion, proliferation and differentiation. Therefore, the identification of these factors is essential to produce the relevant scaffolds.

Polymeric nanofibers for skin regeneration

Nanofibers can be classified into three groups which are: 1.Polymer nanofibers .2.Carbon nanofibers .3.Inorganic nanofibers. Carbon and inorganic nanofibers due to their nature have wide application in various industries but in skin regeneration field, the polymer nanofibers have been investigated in several studies. So, polymeric nanofibers are discussed in this section. Actually over the past decade, scientists have published several articles on innovative wound healing, and some studies have focused on the types of polymer nanofibers and electrospinning, natural, synthetic or blends for skin regeneration. In the next section recent studies on the role of electrospun polymers for skin renovation is assessed.

Cellular scaffolds with natural polymers

Silk fibroin (SF) scaffold

Silk fibroin (SF), a natural protein polymer extracted from animals such as insects and spiders, is widely used as cosmetics, food additives and nanofibers. silk fibroin was also created by silkworms with favorable properties in biomedical applications such as wound healing and tissues repair with controllable degradation rates from hours to years [39]. Biocompatibility, biodegradability, good mechanical properties, resistance to enzymatic activity, the oxygen permeability, are some of the SF properties [40]. In addition, hydrophobicity and hydrophilicity of scaffolds have significant effects on the growth of epidermal cells, the higher the content of the hydrophobicity, the easier for the formation of nanofibers scaffold and improved the mechanical energy [41]. So to change SF nanofibers and little change in surface hydrophobicity, Jeong and others have used [O.sub.2] and C[H.sub.4] [42]. Hydrophilicity of the nanofibers is decreased by Methane, while oxygen increases it. The relationship between surface properties of the scaffold and the normal human epidermal keratinocytes (NHEK) and fibroblasts (NHEF) growth has been demonstrated in this study.

Recent article by Zhong and his colleagues studied in the ability of natural polymers such as SF nanofibers in good adhesion and proliferation of cells such as fibroblasts and NHEK [13]. Similarly, Min and colleagues electrospun SF nanofibers using formic acid as solvent [43]. Methanol solution (50%) used for surface treatment of nanofiber for about 60 minutes. Although the porosity of nanofibers decreased by almost 76% to 68% but the data still showed a good interaction between the nanofibers network and fibroblasts. They suggested that SF nanofibers can be useful for biomedical application such as a wound dressing.

Collagen scaffolds

This Biopolymer, at least in 10 forms, can be extracted from animal's skin, tendons, cartilage and bone. Collagen is one of the first polymers used in tissue engineering because of its safety, prevalence in the ECM, no immunogenicity and accessible process of separation from many sources [44].

Collagen fibrils are often found in fibrous tissue, like skin. Collagen nanofibers, alone or in aggregate form tested as a wound dressing [45-47].

Collagen nanofibers, alone or with ECM proteins were prepared and studied by Rho and others [45]. The results showed that the collagen nanofibers treated with type 1 collagen and laminin improve cell behavior and adhesion. Of course, SEM micrograph showed adhesion of NHOK to scaffold without extension of the surface. But the conjugation of laminin to collagen nanofibers led to a better interaction with keratinocytes. Finally, they concluded that collagen nanofibers are a good candidate for application as scaffolds and wound dressing.

Chitin scaffolds

Today, various polymers used for research on skin cells, scaffolds and repair process. Chitin, a large molecule consisting of sugar molecules strung together and one of the most abundant organic materials on earth [48], is a natural polymer found in the skeleton of shrimps, crabs, lobsters and insects. For the first time, chitin has been studied by the French professor Henri Braconnott in 1811. He found chitin in the cell walls of mushrooms [49]. Chitin is being investigated as a scaffold in the studies [50-52] and has special positive qualities to accelerate the wound. The main biochemical properties of chitin in wound healing are fibroblasts activated, polymorphonuclear cell activation, cytokine production, giant cell migration and stimulation of the synthesis of collagen type IV [53].

Blending natural polymers

Essentially, the combination of polymers, both natural and synthetic does to reduce the undesirable properties and obtain the desired properties for polymer mixture. In the preparation of a cell scaffold, natural or synthetic polymers are used alone or in combination. In this section we will refer to the types and the reason for choice of polymers used to make scaffolds for the regeneration of skin cells.

Chitin/ silk fibroin (SF) scaffolding

Chitin and SF and their blended nanofibers were assessed in several studies [54, 55]. To improve the attachment and spreading of cells on the scaffold, mixed polymers of chitin and SF dissolved in hexafluoro-2-propanol (HFIP)[55]. Diameter of the nanofibers reduced from 920 nm to 340 nm with the higher chitin content. To change mechanical properties and water resistance of the mixture, the water has been used to treat the network of nanofibers. Based on the results cytocompatibility test, chitin/SF nanofibers (ratio 25:75) could be a good candidate for tissue engineering scaffolds. Of course the mechanism of interaction between SF and chitin has not been investigated in Park study and is not well understood. But Falini and colleagues had already shown that the silk fibroin intercalates between the molecular planes of the chitin and the interactions are mainly through the chitin acetyl groups. Finally, they deduced that the chitin and protein are not intimately mixed and there is an interfacial plane between chitin and SF and the interactions are through the amide groups [56]

Chitosan (CS) /SF scaffold

Chitosan is a biopolymer derived by deacetylation of chitin with wide application in biomedical science because of its abundance, safety and antibacterial behavior. The mix of CS and SF nanofibers was built as a antibacterial wound dressing [57]. Concerning the mechanical behavior, the SF rate directly affected the mechanical properties of CS/ SF nanofibers. The antibacterial activity of nanofiber mats against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) were estimated using the turbidity method. The composite nanofibers showed different antibacterial activity. In addition, the in vitro biocompatibility of composite scaffolding examined by culture of mouse fibroblast in hematoxylin and eosin (H & E) staining and MTT assays. The promotion in the cell attachment and proliferation was seen in the nanofiber mats. The promising results suggested suitable coverage of wounds using CS/SF nanofiber membranes.

The chemical interaction between CS and SF of the blend was investigated by Baimark and the others [58]. The result of The FTIR and TG tests showed that the intermolecular interactions had occurred. The conformation of SF changes from random coil to a-sheet forms and the increasing thermal stabilities of the CS were detected by blending of SF and CS. Also results showed that the increasing molecular weights of the CS increased interactions between SF and CS in the blend films and SF/CS blend, in addition to its application as a scaffold, might be of interest in biomedical, pharmaceutical and packaging applications.

Chitosan /gelatin scaffold

Mixing the two types of natural polymers as cell scaffolds may advise us on how to overcome some known problems such as low mechanical strength. For instance, nanofibers were smooth variables from 120 to 200 nm produced by mixing chitosan and gelatin [59]. The mixture strength (37.91 [+ or -] 4.42 MPa) was significantly greater than the gelatin nanofibers alone (7.23 [+ or -] 1.15 MPa) (p < 0.05) and was close to natural human skin. So, chitosan has the ability to improve low tensile strength of gelatin nanofibers.

In addition, the chemical modification of natural polymers such as polysaccharides and proteins is a promising way for the development of scaffolding to make good use of their inherent biodegradability and biocompatibility. Of course the CS/gelatin mixtures can be prepared in cross-liked and non cross-linked manner. Kim and colleagues study showed that cross-linked networks of were stable in water, and had improved mechanical properties and thermal stability compared to non cross-linked CS/gelatin mixture [60]. On the other hand cytocompatibility of gelatin modified chitosan in CS/gelatine mixture has been improved shielding of the positively charged chitosan to a proper charge density. The environment PH is another important factor that influences the interaction chitosan and gelatin. CS is a pH-sensitive polymer which can be protonated amino groups depending on the pH of the environment. When CS is mixed with ampholytic gelatin, when the pH of the medium above the isoelectric point of gelatin, which is a negative charge, the electrostatic interaction occurs between the ammonium ions of CS salts and carboxylic groups of gelatin [61].

Performances of composites as wound dressing have been tested by the others. Scherer and colleagues produced PolyN-Acetyl Glucosamine nanofibers and assessed effects on diabetic ulcers care under in vitro and in vivo [62]. The results are shown stimulation of metabolism and migration of fibroblasts and endothelial cells in culture media. Based on the results re-epithelialization and keratinocytes migration (7.5-fold), the formation of granulation tissue (2.8-fold), cell proliferation (4-fold), and vascularization (2.7-fold) increased in experimental groups compared to control groups. In wounds treated nanofibers expression of angiogenesis markers (VEGF), cell migration (uPAR) and ECM remodeling (MMP3, MMP9) were up-regulated. Finally, they concluded that sNAG nanofibers have a positive effect on defects of complex tissue.

Synthetic polymer scaffolds

Poly ([epsilon]-caprolactone) (PCL) scaffolds

PCL is a biodegradable polymer with hydroxyl end group and derived from the chemical synthesis of crude oil. It is a thermoplastic polymer with a glass transition temperature of about "60[degrees]C and low melting point about 60[degrees]C.

In use of PCL as electrospun scaffold for skin renovation, Reed and colleagues have fabricated PCL nanofibers and seeded human foreskin fibroblasts and murine keratinocytes on it [63]. Cell growth was evaluated by fluorescent staining viability. Even cell cultures were differentiated by the use of antibodies against specific surface markers of fibroblasts and keratinocytes. The data are well-established a strong growth of keratinocytes and fibroblasts on PCL scaffolds. Also co-culture of fibroblasts and keratinocytes enhanced lifetime of keratinocytes.

Concerning use of PCL as a scaffold for wound care, Choi and his colleagues invented PCL nanofibers with an immobilization human epidermal growth factor (EGF), for the treatment of diabetic ulcers [64]. For the assessment of EGF effects on human keratinocytes differentiation, EGF chemically conjugated to the surface of the mixed copolymers of the PCL and polyethylene glycol (PEG) nanofibers. The data have supported higher wound healing in EGF-nanofibers compared to control groups or EGF solutions in vivo. The results showed a significant increase in keratinocyte-specific genes expression. Also, immunohistochemical staining procedure results explained higher expression of EGF-receptor (EGFR) in EGF nanofibers scaffold.

Finally, this study supports the potential ability of EGF-conjugated nanofibers, as wound dressing for greater expansion and phenotypic expression of keratinocytes.

Poly (lactic-co-glycolic acid) (PLGA) scaffolds

In the use of biodegradable polymers in skin regeneration Li and colleagues used PLGA, which has been synthesized in their laboratory [65]. PLGA is a copolymer composed of polylactic acid and polyglycolic acid hydrolysis to monomers in the body than to lactide [66] and glycolide [67]. Systemic toxicity from PLGA in biomedical applications is low. The PLGA copolymer was used as scaffolds and mechanical resistance amplifier in mechanically weak nanofibrous scaffolds such as collagen [68]. Also, Yang and his colleagues in the research show considerable mechanical strength of electrospun collagen nanofibers to increase with the addition of PLGA copolymers [69].

To improve skin vitality and cell migration, Li and colleagues increased porosity of scaffold using a slow-rotate cylinder collector in electrospinning. They cultured human dermal fibroblasts (HDFs) on PLGA scaffold and observed higher collagen deposition, cell migration and viability by increasing the porosity. As mentioned above, PLGA nanofibers have a high mechanical strength to ensure a uniform distribution of dermal fibroblasts, when they were applied as a scaffold for skin renewal. So nanofibers with higher porosity can be a better performance as a dermal scaffold.

With respect to the near relationship between nanofibers diameter and cell proliferation in the skin scaffold, PLGA nanofiber scaffold was prepared for skin tissue engineering [12]. PLGA nanofibers spun from 150 nm to 6000 nm. The relevant diameter of the nanofibers for increasing proliferation was about 350 to 1100 nm. The results showed well-formed cells network in PLGA nanofibers 28 days after cell culture, and efficiency of scaffold for skin repair process.

Scaffolding in 3-dimensions (3D) was made by researchers [70-72]. There are technological limitations in generating three-dimensional scaffolds by common electrospinning method. So Kim and co-workers was fabricated 3D PLGA scaffold by the new hybrid electrospinning and melt electrospinning methods. In some previous studies, other methods have been designed for 3D electrospun scaffolds [73-75]. Kim and colleagues produced nanofibers (mean diameter= 530 nm) and microfibers (mean diameter= 28 [micro]m) randomly oriented. The data showed significantly higher attachment, the proliferation and infiltration of normal human epidermal keratinocytes (NHEK) and normal human epidermal fibroblasts (NHEF) on hybrid micro/nanofibers than microfibers without nanofibers. Thus they concluded that 3D hybrid micro/nanofibers have the ability to use in tissue engineering. With respect to strength PLGA nanofibers as scaffolds [38, 76, 77], shin and colleagues examined the relationship between tensile strength and the ratio of the monomers in PLGA scaffold [78].The modulus of elasticity of the scaffolds were almost like the skin, and was slightly lower than human cartilage on different ratio (lactic/glycolic acid ratio = 75 : 25, 50 : 50).

3D Collagen scaffold

Diameter of the scaffolding nanofibers effect on the responses of cells, collagen 3D scaffold has been designed as the tissue renewal agent [79]. Cryogenic distribution system was used to make collagen scaffolds with high porosity. Laboratory results showed a good dispersion of fibroblasts into the scaffold and the relevant keratinocytes migration through the porous scaffold. Like the normal skin tissue, differentiation of keratinocytes on the collagen scaffold was suitable and made a stratum corneum layer in collagen 3D scaffolds. The data are compatible with collagen 3D scaffold as a skin recovering substance.

PolyL-lactide (PLLA)/ poly (D, L) -lactide-co-glycolide (PLGA) scaffold

The biodegradable nanofibers are extensively used as an artificial dermis [80, 81]. In the production of artificial dermis, Blackwood and collaborators produced six scaffolds include polyl-lactide (PLLA); PLLA+ 0% oligolactide; PLLA+ rhodamine and three poly (D,L)-lactide-co-glycolide (PLGA) multiblock copolymers with random mole ratio of lactide/glycolide fractions (85:15, 75:25 and 50:50). Electrospun nanofibers were assessed at the rate of degradation in vitro and in vivo in adult male Wistar rats. All scaffolds allow good cellular penetration without damaging inflammatory reaction and capsule formation around the edge. The level of decomposition was near the scaffold in vitro unlike in vivo, and an increase in the level of degradation was observed with an increase in the ratio of polylactide to polyglycolide. PLLA scaffolds showed good stability after 12 months in vivo.

The PLGA scaffolds, 85:15 and 75:25 lactide/glycolide molar fractions ratio showed a 50% weight loss after 4 and 3 months. The Scaffolds supported ECM keratinocytes, fibroblasts and endothelial cell growth, confirming the production of new collagen after 7 days. Finally, the results explain the relevance of PLGA nanofibers scaffolds as potential degradable artificial dermis.

A key factor in tissue engineering includes design scaffold and interaction of cells with the scaffold [82]. A change in cellular interactions and scaffolding, are some of the techniques used to improve cells infiltration of three-dimensional scaffolds, such as biochemical and biophysical changes.

PLLA nanofibers with 3D shape significantly increased infiltration of endothelial cell under both in vitro and in vivo [83]. The biochemical modification of PLLA scaffold, heparin coating, significantly increased cell infiltration into nanofibers. Also, adding collagen, increased hydrophilicity of nanofibers, cell attachment and proliferation [84].

Poly (ethylene-co-vinyl alcohol) scaffold

In an effort to produce innovative scaffold for skin wound healing, Xu and his colleagues produced Poly (ethylene-co-vinyl alcohol) nanofibers encapsulated Ag nanoparticles [85]. Poly (ethylene-co-vinyl alcohol) with good mechanical properties, biocompatibility and biodecomposability dissolved in different concentrations of ethylene vinyl alcohol copolymer (EVOH) with AgN[O.sub.3]. The results showed that the fibers have good antibacterial properties and ability to control inflammation. They suggested that Poly (ethylene-co-vinyl alcohol) nanofibers may be a candidate for applications in the treatment of skin wounds.

Blending natural/ synthetic polymers for skin regeneration

Collagen/ PCL scaffold

As engineered polymeric composites for the skin, were mixed collagen and polycaprolactone (PCL) nanofibers used as a dermal scaffold [86]. PCL nanofibers with biodegradability and biocompatibility properties coated with collagen and showed apt fibroblasts growth, expansion and migration in the laboratory, and indicated the desired properties as artificial ECM.

The use of collagen in association with PCL, makes scaffolding more closeness with the fluids of the body, so providing hydrophilic interaction. Collagen scaffolds are poorly permeable to water vapors, thereby, they are considered occlusive. So, Collagen biomaterials with polycaprolactone used in the preparation of the new scaffolds are expected to possess good biocompatibility for wound tissue [87].

PCL has significantly various biomedical applications such as low antigenicity and mechanical flexibility, easy processability, and chronic low-level persistence [88].

As mentioned, one of the synthetic polymer used as skin cells scaffold, is PCL. [86]. PCL, a bioresorbable polymer with notable stability, has been used as wound care dressing in research since 1970. It is a suitable candidate for tissue engineering and dermal care. The mixture of PCL and collagen type 1 (55:25 mg / ml) dissolved in a solvent and willing to electrospinning. The applied voltage was 13 kV with 900/ h rations. Nanofibers diameter was about 170 nm. This network of nanofibers wound healing promoted by adhesion, attachment and proliferation of fibroblasts. The results showed that PCL/ collagen nanofiber, as a dermal substitute, is a good candidate for the treatment of skin lesions and wound care.

Also, Heather and co-workers mixed PCL/collagen nanofibers [46]. Due to poor mechanical strength of collagen nanofibers, PCL added to improve the strength of nanofibers. At concentrations <10% PCL, the PCL distributed on the collagen matrix, but by increasing the proportion of PCL to 30%, separation occurred between collagen and PCL phases. Increased concentration of PCL from 10 % to 100% led to improve in nanofibers tensile strength. At a concentration up to 10% PCL, engineered skin (ES) had no significant effect on cell proliferation and differentiation of epidermal compared to nanofibers with 100% collagen. The results showed that the collagen-PCL blend had promising tensile strength, almost equal to ES made of 100% collagen. The PCL (30%) groups indicated low mechanical properties, the formation of the epidermis, and cell viability. The data showed no significant increase in the strength of scaffold with a higher level of PCL in the ES. Finally study confirms the importance of factors such as strength, cell viability and development of artificial skin epidermis. PCL and PCL/collagen nanofiber matrices immobilized with EGF for the regeneration of damaged skin, have been carried out successfully by electrospinning [89].

As indicated in the results, PCL and PCL/collagen nanofibers had a diameter of about 284 [+ or -] 48 nm and 330 [+ or -] 104 nm respectively. The PCL porosity were approximately 85% and 90% for PCL/collagen matrices and EGF immobilized PCL/collagen matrices indicated early cell proliferation and rapid spread. They concluded that EGF immobilized PCL/collagen nanofibrous mats can be a dermal substitute and alternative for the treatment of skin wounds for applications in tissue engineering.

PCL/gelatin scaffold

Gelatin, a natural polymer, is a mixture of proteins and is obtained from the hydrolysis of collagen in cattle and sheep skin, tendons, and so on. Following previous research, a polymer of PCL/gelatin mixture is a new biomaterial with a good biocompatibility, physical and chemical properties. In justifying the mix to make this scaffold, the quality of cellular scaffolds made of gelatin and PCL alone or in combination was studied. The result of Contact-angle measurement and tensile tests have shown that the membrane gelatin/PCL fibrous complex exhibited improved mechanical properties and wettability is more favorable than that obtained from either gelatin or PCL alone that could be enhanced cell adhesion to the scaffold [90].

Chong and colleagues made PCL/gelatin composite scaffold due to its affordable price [91]. They said the high price prevents widespread use of artificial skin. Polyurethane, a biodegradable polymer that degrades by hydrolysis and enzymatic chain based cleavage [92], was used as a base for PCL/gelatin scaffold as a wound dressing. The electrospinning parameters were 10-ml syringe with a tip diameter of 0.4 mm, 10.5 kV and 15 cm distance between the syringe and collector and 0.7 ml/h feed rate of the polymer solution. Average diameter of nanofibers nearly 470 [+ or -] 120 nm with a porosity 6275% rate of fibroblasts seeded and well populated. The results represented the feasibility of cell culture scaffolds for repair of the skin, and usefulness of scaffolding PCL/ gelatin in the treatment of skin wounds.

Polyurethane (PU)/ gelatin scaffold

PU is classes of synthetic polymers that are produced by react between polyols and isocyanates as part of the original PU. First time PU polymers were discovered by Otto Bayer and his colleagues in the AG FARBEN lab in Leverkusen, Germany in 1937. PU is biocompatible with good mechanical properties and used as a blood storage bags for many years.

Kim and colleagues have prepared nanofiber scaffold with a mixture of natural and synthetic polymers, PU and gelatin by electrospinning method to prepare a scaffold for medication [93]. In fact, the logic of this mixing may be providing mechanical support by the PU polymer while gelatin provides accommodation for implant cells.

From the results, reducing gelatin ratio in the mixture led to increased contact angle and decrease of wettability that can reduce the likelihood of cell adhesion to the surface of the scaffold. While, the mechanical tests showed that scaffolds are elastic and elasticity is increased by higher amount of PU in the mixture. Concentration of gelatin also had a direct effect on the cell proliferation with the same amount of time the cultivation. They concluded that the gelatin/PU nanofiber scaffold has potential application for use as a wound dressing.

Collagen/chitosan and polyethylene oxide (PEO) scaffolding

A mixture of natural and synthetic polymers to improve nanofibers properties have been used in some of the articles. PEO or poly(oxyethylene), a synthetic polymer, is able to improve the applicability of some natural polymers such as collagen/elastin blend [94] and fibroin [95], in electrospinning. PEO is approved by the FDA for use in various pharmaceutical formulations, foods, and cosmetics and is a nontoxic, amphiphilic and soluble in water as well as in many organic solvents.

Mixture of collagen and chitosan, natural polymers, to form nanofibers was evaluated by Chen and colleagues [96]. Mixture of such polymers cannot form nanofibers network because of their large network charges. When the charge density is too high in electrospinning, the jet of polymer becomes highly unstable. On the other hand, when the charge density is too low, the solution drips. Therefore, there is an optimum charge for stable spinning without disruption of the solution [97]. Hence, to reduce the conductivity, PEO was added to the chitosan/ collagen mixture with an effort to decrease the conductivity of the solution.

Glutaraldehyde was also used for the cross-linking of nanofibers. The results indicated that collagen has a major influence on the conductivity compared to the PEO with the least impact. In addition, chitosan has had more influence on the viscosity of the solution. The best condition for electrospinning was voltage = 30 kV, flow rate = 0.5 ml / h, mass ratio of collagen/chitosan = 1 / 3 and collector to needle opening = 25 cm. Average diameter of nanofibers were measured approximately 134 nm and 398 nm for original and cross-linked nanofibers respectively. The results showed a good biocompatibility and the proliferation of fibroblasts in the nanofibers network and, finally, a good effect of collagen / chitosan nanofibers on cell migration and wound protection of commercial collagen sponge.

Gelatin/ poly (L-lactide-co-a-caprolactone) (PLCL) scaffolds

Gelatin, a biopolymer gains from bones and skin, are used alone or as a mixture of scaffolds for tissue engineering.

But it is often used in composite form due to poor mechanical properties [98]. In a study, a mixture of gelatin and electrospun PLCL was to produce a skin graft. Blended ratio was 0, 30, 70 and 100 % by weight of gelatin to PLCL. The average fiber diameters of which were about 50 to 500 nm. The contact angle and tensile strength reduction and initial cell adhesion and proliferation enhancement was observed due to an increase in the ratio of gelatin nanofibers. The results indicated that the gelatin/ PLCL nanofibers can be a useful candidate to restore damaged skin [99]

Collagen/ polyglycolic acid (PGA) scaffold

To get the desired response of cells from a biomaterial, chemistry, mechanics, and structure of the material should be optimized. In most cases, these properties should be designed to create a suitable environment for controlling cell adhesion and attachment. The synthetic biodegradable polymers, such as the PGA and its copolymers have been made in the scaffolds for tissue engineering applications. However, few studies on the use of scaffolding in skin reconstruction have been done.

Tian and co-workers produced composite of PGA and collagen for management of the skin [100]. Although the biocompatibility and biodegradability of the mixture, cell adhesion and cell growth were unknown in these nanofiber scaffold, but by increasing fiber diameter from 500 nm to 3.5 microns and 10, the number of fibroblast cells attached to scaffolds significantly decreased. Moreover, the morphological observation of nanofibers represented only with 40% of the PGA in the mixture the highest cell growth and attachment was occurred. Finally, the results showed that PGA/collagen nanofibers can be used as a scaffold for the management of the skin.

Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), (PHBV)/collagen, (PHBV)/gelatin scaffold

Safety assessment of wound healing by biopolymers was examined by experts. Thus, PHBV

nanofibers in the early stages of wound healing evaluated [101].

PHBV, a copolymer of microbial polyester, is a good choice for use as a scaffold. In this study, nanofiber scaffolds divided PHBV, PHBV / collagen and PHBV / gelatin group, with 7 / 3 weight ratio of PHBV to collagen and gelatin, produced by electrospinning. Follicular epithelial cells, keratinocytes of the root sheath (ORS) and cells of the dermal sheath (DS) were grown on a scaffold and examined under in vitro and in vivo. Han and his colleagues used these cells instead of keratinocytes and fibroblasts because of the critical role of the hair follicle to regenerate the skin. When skin is damaged in mammals, the follicle and epidermis recovers re-epithelialize using self-renewal of the system: the pool of stem cells [102]. In addition, the dermal sheath cells and progenitor cells are able to maintain and regenerate the papillary dermis and fibroblasts [103].

The results shown quick growth of the skin sheath (DS) cells hydrophilic PHBV / collagen and PHBV / gelatin nanofibers compared to hydrophobic PHBV nanofibers at the start of incubation (up to 6 hours). Also, from 6 to 24 hours of incubation, PHBV / collagen matrix showed the best results in cell culture. There was no significant difference between PHBV and PHBV / collagen expressed cytokeratin 8.

Finally, the results suggest that PHBV co-cultured with ORS / DS cells can be used as a biological dressing for wound healing during the early phase.

Chitosan/polyvinyl alcohol (PVA) scaffold

As mentioned above, chitosan, (poly-a(1,4)-D-glucosamine), a cationic polysaccharide derived from chitin, which was produced in 1859, has broad applications in biomaterials and biomedical domain [104-107].

Wound dressing is very promising application of chitin and chitosan [108], with regard to the antimicrobial and antifungal properties of chitosan [109] [110]. Actually, for enhancing cell attachments and infiltration, chitosan was mixed with one or more natural polymers.

Natural polymers such as chitosan, in the preparation of compounds desirable for biomedical application, has been mixed with other polymers such as gelatin [111], and collagen [112] [113]. Collagen, the major polymer exists in a native ECM multifibril 3D mesh, mixed with gelatin/ chitosan and electrospun biomimetic as ECM for endothelial cells [114]. This scaffold has shown good efficacy in skin and tissue engineering. Even mixed chitosan with other polymers such as PVA as wound coverage has been studied [72].

Polyvinyl alcohol, a synthetic resin, is a biocompatible and water-soluble polymer with high elasticity.

PVA has good chemical stability, film-forming ability and high hydrophilicity. Moreover, since PVA is biocompatible polymer and nontoxic, and exhibits minimal cell adhesion and protein absorption, so according to researches results on relevant properties of chitosan and PVA, its blend has shown good mechanical properties [115].

Chemical interaction between PVA and chitosan improves tensile strength (TS) and reduces elongation rate of the mixture that could be because of interaction between--OH and -N[H.sub.2] groups of chitosan and -OH groups originated from PVA. In addition, the wettability of the CS/PVA mixture is increased with increasing PVA content in the blend that can increase the likelihood of cell adhesion to the scaffold [116].

Chitosan / PCL scaffold

Recently cationic nanofiber mats, chitosan (CS) are grafted (g) to PCL [117]. The results are explained promote attachment and cell proliferation, and showed that CS-g-PCL/PCL scaffold can be a relevant candidate for use as an agent of tissue engineering.

From the chemical viewpoint to ensure the maintenance of antimicrobial power of chitosan in the mixture, Studies had already indicated no chemical bond formations in the mixture, also wide-angle X-ray diffraction (WAXD) showed that the crystal structure of individual polymers was unchanged in the mixture [118]. Therefore, CS/PCL mixture not only does not change desired properties of polymers but also improves overall features of polymers as cell scaffolding. As the increased viability and redistribution of actin fibers was observed in the mixtures formed with 50% PCL and 75% PCL relative to individual chitosan and PCL. Moreover, when mixtures 50:50 processed at 55[degrees]C in an oven showed significant improvement in mechanical properties as well as support for cellular activity in relation to chitosan [119].

Nanofibers and drug delivery for Skin care

The wound must also be relatively uncontaminated by bacteria. Bacterial contamination rate of about 100,000 square centimeters linked to high risk of graft failure. In addition to tasks such as debridement, dressing changes, topical antibiotics instead of systemic may be indicated prior to grafting. Therefore, drugs can be used topically in the form of nanofibers. What are the benefits of using nanofibers as drug delivery systems?

The traditional drug delivery systems do not have specific objectives with a lack of release control. This means that over time, significantly, the concentrations of the drugs, the recommended maximum value, [C.sub.max], exceed the risk of biotoxicity, or fall below the minimum effective concentration, [C.sub.min], reduce healing. On the other hand, the distributions of the drug in all organs of the body are passively. So for the delivery of optimum concentration, [C.sub.opt], of drugs in the tissues should be maintained in the total treatment time. In drug delivery verifiable, the bioavailability of the drug is closer to the highest level throughout the target organ compared to traditional drug delivery. Therefore drugs administered will be lower than in an uncontrolled release method and thereby reduce the risk of side effects.

Generally, drug delivery by polymers can be controlled by diffusion or chemical form (by bio-erosion or biodegradation of the links between drug and the matrix or the matrix). The reader is referred to many good comments on the use of polymers for controlled drug delivery [120-122] .

Mainly it is the nature of semi-crystalline polymer and the morphology of the polymer / drug composite control the release kinetics of drugs. First, Kissel and colleagues considered three models of the drug-loaded polymer morphology [123] and a decade later Verreck and collegous confirmed a similar article published in the amorphous drug-loaded nanofibers [124]. These patterns of drug-loaded polymers are:

Dissolution of the drug in the polymer matrix at the molecular level.

Distribution of drug particles in the polymer matrix as crystalline or amorphous.

Closure of drugs in the polymer matrix, allowing the drug core encapsulated by a polymer layer.

As respects the skin regeneration, wound treatment depends on many factors, such as the condition of patients, type and severity of the wound, physical and chemical properties of wound dressings, medications and so on [125]. Nanofiber scaffolds as new drug delivery agents have a number of benefits including reduced potential for systemic toxicity, improve the timeliness and economic efficiency [126]. Alarge surface area, the ability to use various substances, both controlled and sustained release of drugs (by diffusion alone or diffusion and the degradation of scaffolds), are other advantages of nanofibers as novel drug delivery systems.

Some biomedical researchers have reported the use of specific types of bioactive ingredients in the nanofibers to investigate their benefits in the treatment of wounds [124, 127].

There are many studies confirm the advantages of nanofiber-based drug delivery in the last decade [128-130]. More recently, scientists have used electrospun nanofibers specific active compounds as safety bioactive materials. Antimicrobial agents [3], silver nanoparticles [131], zinc oxide (Zno) [132], and shikonin [133] are used in some recent studies, and their positive effects on wound healing has been shown.

Variety of polymers, natural or synthetic, has been used for drug delivery into the wounds. SF with excellent mechanical properties, biocompatibility, biodegradability and workability has been used as drug delivery agent in skin care [134]. From the results, some properties of drugs such as molecular weight, crystallinity, concentration and structure variables are suggestive release kinetic parameter matrices SF as a reservoir of drug.

As mentioned above, the silver nanoparticles, is an antimicrobial agent [135], was used in a variety of nanofibers with potential applications such as scaffolding. A mixture of silver nanoparticles with PVA / chitosan nanofibers explained better than antibacterial activity with PVA/ chitosan nanofibers without silver nanoparticles. The use of silver nanoparticles in PCL / ascorbyl palmitate (AP) nanofibers have shown antibacterial and antioxidant activity [136].

Recently, Ma and co-workers evaluated antimicrobial activities of silver nanoparticles in an innovative inorganic nanofiber mat. They made an inorganic Si[O.sub.2] nanofibers include silver nanoparticles as wound dressing. They expressed the polymer nanofibers made of organic materials usually unable to remove impurities from the burn wounds, and are not subsequently reusable. So they grafted Si[O.sub.2] nanofibers and silver nanoparticles (Ag NPs) on the fiber surface and evaluated antibacterial effects. Their results showed that the Si[O.sub.2] nanofibers are soft and flexible and can easily be model non-woven film. The SiO2 nanofibers grafted Ag NP efficiently inhibits the proliferation of the Escherichia coli (E. coli) with antibacterial effects in the long-term. More importantly, this coverage has been extended inorganic antibacterial wound through calcinations without loss of flexibility and antibacterial effects. So, the results showed that Ag NPs and Si[O.sub.2] nanofibers grafted meet to dress the wound treatment reusable [137].

In contrast to the favorable properties of silver nanoparticles as an antibacterial agent, potential toxicity has been studied [36, 138]. Therefore, heat-treated PVA loaded with silver nanoparticles, was used as a epidermal cells scaffold and showed a deleterious effect on growth, attachment and spreading of NHEK and NHEF cells [139]. In similar study, Poon and Burd suggested that silver has a high toxic effect on fibroblasts and keratinocytes in monolayer culture [140].

So researchers are looking for alternative biocompatible materials with antimicrobial and anti-inflammatory effects, such as plant extracts to be used as agents of wound healing.

Extracts of plants have been used by researchers as the wound healing agents in electrospun nanofibers. Sikareepaisan and colleagues successfully electrospun gelatin nanofibers containing the herbal extract, methanolic crude extract from Centella asiatica (L.) Urban , a planet with the capacity for therapeutic wound healing [141]. Likewise, Vargas and co-workers have built an active agent delivery applications for wound healing by electrospinning hyperbranched polyglycerol (HPGL) [142]. The purpose of this work was to prepare nanofibers HPGL contains Calendula officinalis, a plant of the genus calendula (pot marigold) Astraceae family, as wound healing and anti-inflammatory agent. The results showed the release rate of c.officinalis depends on HPGL proposed content, and in vivo experiments on rats have suggested that HPGL-C officinalis can be a good candidate as wound dressing.

One of the polymers useful in the biopharmaceutical industry is cellulose- based materials such as cellulose acetate [143]. Nanofibrous form of cellulose acetate have been used as a topical and transdermal delivery of bioactive materials, such as curcumin [144], and asiaticoside centella asiatica [145], non-steroidal anti-inflammatory drugs [146], vitamin A and vitamin E [147].

For example, Suwantong and others loaded plant-based extract, curcumin, with good antioxidant and anti-inflammatory properties in CA nanofibers mats and confirmed its nontoxic effects on normal human dermal fibroblasts (NHDF) [144]. Another plant extract, shikonin, an agent of wound care with significant anti-inflammatory, antimicrobial, antioxidant and anti-tumor properties, is used in nanofiber mats [148].

Kontogiannopoulos and co-workers designed a network of electrospun nanofibers containing shikonin and investigated its efficacy in wound healing. Biocompatible scaffolds, CA, PLA and PLGA containing shikonin, have a attraction for promising tissues repair and management of the skin [133].

Han and colleagues have developed PCL / polytrimethylene carbonate (PTMC) nanofibers that has been applied as drug delivery for encapsulation of herbal medicine shikonin with the good stability and high-loaded efficacy. Shikonin did not alter the morphology of the nanofibers in both the shikonin-free and shikonin-loaded nanofibers. The in vitro release behavior can be adjusted shikonin ratio in the PCL/PTMC fibers and drug-loading content. Finally, the result of free radicals scavenging and antibacterial activity of shikonin-loaded fibers suggested that it may be active both as a drug delivery and wound healing agent [149].

And later, fucidic acid (FA), a bacteriostatic antibiotic used to treat wounds. FA is gained with the fungus Fusidium coccineum by Leo Laboratories in Ballerup in Denmark and released for clinical use in 1960s [150]. Said and colleagues loaded FA into the biodegradable PLGA scaffold and see its advantages in the removal of planktonic bacteria [151].

The cross-linking and the polymer scaffolds

The cross- linking process means breaking some covalent or ionic bonds in the polymer chains and establishing new links. Polymer chains can refer to natural polymers (like proteins) or synthetic polymers. Beside mixing two or three natural or synthetic polymers and producing a new biocomposite to improve biochemical properties of nanofibers [152], this is done to improve the physical or chemical properties of polymers such as higher tensile strength and thermal resistance or lower solubility. Indeed, the cross-linking used to adjust the stability of natural or synthetic polymer nanofibers [13]. The cross-linking is one of the most important methods for fixation mechanical stability, degradation and swelling of the aqueous polymer scaffolds. There are several methods for cross-linking of polymers in the nanofibers as chemical cross-linking structure includes use of genipein [153], glutaraldehide [127] and physical cross-linking includes photo cross-linking by UV radiation [154] and hydrothermal treatment [155]. Even low- risk and safe methods such as use of water steam and heating to cross- linking is recommended.

In a study Min and colleagues used SF as a dermal scaffold with differences in the treatment of the SF nanofibers network using water vapor instead of methanol, as cheaper and safer material, the transition from the SF-formation led by the random coil to a sheet, and deep changes were dependent on both the treatment time and temperature. With regard to water safety, the cytocompatibility analysis explained promising composition for fibroblasts and keratinocytes than methanol-treated SF scaffolds. They concluded that such nanofibers can be improved the ulcers as a wound dressing [156].

Stem cells and the future of the skin regeneration

Stem cells have unique capabilities, such as renovating of organs throughout the life span and produce daughter cells differentiate into one or more line [157]. Mesenchymal stem cells (MSC), multipotent stem cells with the ability to differentiate along the epidermal lines on nanofibrous scaffolds, have a great capacity for the treatment of skin wounds.

As already mentioned, a suitable artificial extracellular matrix (ECM) is essential for cell adhesion, proliferation and differentiation to replace and repair damaged skin [158]. As well developed nanofibrous scaffolds closely with stem cells (SC) and the response to many signals from the extracellular microenvironment. For attachment to synthetic nanofibrous mats, SCs has shown promise in regenerative medicine and skin management. The cultivation of SCs through scaffolding supporting the benefits, such as filling the space, support for the treatment of skin ulcers [159].

The experimental evidences support the good interaction between nanofibrous matrices and SCs before or after implantation in vivo [160]. Through the skin to repair by MSCs, recently Jin and colleagues have produced nanofibrous scaffold made of collagen/poly(L-lactic acid) -co-poly (3-caprolactone) (Coll/PLLCL) [161]. The results showed that MSC differentiate at the Coll/PLLCL nanofibrous scaffolds, and concluded that it is promising scaffolds as a substrate in the native skin repairing without regional differentiation trend.

In another study, the PCL fibers scaffolds and chitosan biocomposite were obtained. The biological response of MSCs in the biocomposite was investigated. Observations supported that chitosan / PCL nanofibers can be an excellent scaffold in tissue engineering [162].

Future regeneration of the skin with the potential power of the research depends SCs. Recently some experiments results have supported the effectiveness of stem cells in nanofibrous scaffold in biomedical applications such as bone reconstructive vascular tissue [163], cardiac tissue [164], the treatment of cardiovascular disease [165], neural SCs [166], cartilage engineering [167] and tendon regeneration [168], published and ensure a promising future in the biomedical application of nanofiber scaffold in skin restoration.

And, finally, we will use to develop nanofibrous scaffold as a promising active ingredients in both wound healing and skin regeneration in the near future.

Conclusion

Skin injuries impose a heavy cost to patients and communities each year. Today, deep skin wounds are done with the use of expensive surgery with unbearable and severe pain for patients. Alternative non-invasive and less costly ways to help patients in several researches is being investigated. One of these research areas is the use of nanofibers

Biomedical fields are influenced by new materials and technologies. Nanofibers, A new and exciting class of materials have practical application in the biomedical field. Damage to the skin has serious consequences for human health and need for speedy recovery. On emerging technology trends, polymer nanofibers biomaterial-based for wound dressing with numerous benefits is desirable not only for patients and medical team, but also for national authorities and public health organizations.

This paper describes the common terms such as nanofiber, skin layers and the conventional method to prepare nanofibers, electrospinning, and the types of polymers used in the past decade researches. Research has been used in various types of natural and synthetic polymers and their mixtures for coatings skin injuries. Nanofibers from natural polymers such as gelatin, chitosan and chitin are many benefits to the treatment of skin injuries but their use has restrictions. Expensive purification method of these polymers is one important factor in the application of these fibers. The unique properties of natural polymers such as biocompatibility and biodegradable and their application in medical skin coverings guarantee their safety and applicability. On the other hand, was cheap and good mechanical properties of is the advantages of synthetic polymers. Appropriate mix of natural and synthetic polymers, not only improves biological and mechanical properties but also reduces nanofibers prices, so these products will become cheaper and more economical compared to natural polymer nanofibers.

We introduced our readers with a variety of polymers have been investigated in skin regeneration by a review of articles have been published during the past decade. This review would be very appropriate for researchers that work in the field of nanofibers skin care, also, manufacturers of cosmetics and skin patches to meet a variety of materials used in such products and their benefits.

Finally, after numerous advantages of polymer nanofibers in medicine, author believes that more attention to be focused on the scope of science

Acknowledgment

The author wishes to express his gratitude to Research Centre of Reproductive Science authorities specially Prof. Abbas Aflatoonian to provide appropriate conditions for research. Also the author would also like to convey thanks to the Shahid Sadoughi University of Medical Sciences authorities for all the supports.

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Majid Naghibzadeh *

Departments of Nanotechnology, Research Centre of Reproductive Science, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

* e-mail: mnaghibzadeh@razi.tums.ac.ir

Received 16 February 2012; Accepted 18 March 2012; Available online 27 April 2012
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Title Annotation:Short Communication
Author:Naghibzadeh, Majid
Publication:Trends in Biomaterials and Artificial Organs
Article Type:Report
Geographic Code:7IRAN
Date:Apr 1, 2012
Words:13899
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