Nanofibers for Skin Regeneration and Wound Dressing Applications

Abstract

The regeneration of skin because of numerous sorts of injuries such as burns, wounds, tissue damage, and eczema is regarded as vital; nevertheless, the process of healing and remodeling can be impeded by several reasons. The cutting-edge of nanofibrous technology offers the opportunity to repurpose and innovate new therapies and improve the effectiveness of the available medical treatments. There may be less need for skin transplants and skin grafts as regenerative medicine advances using biopolymeric materials. Skin injuries can be difficult to treat, especially when it comes to managing wounds. The fabrication of different dosage forms such as film, foam, sponge, hydrogel, and nanofiber membranes using scaffolding material made from synthetic and natural polymers is considered a treatment method for wounds. Scaffolds have found applicability in tissue engineering, where the materials are fabricated into artificial tissue that stimulates growth factors and enhances tissue regeneration. Among these materials, nanofibers possess a unique structure of small pore size and high porosity, thus protecting wounds from infections and ensuring unrestricted transportation of gas and liquid molecules. We have described several polymers in this study that have been used to create scaffolds made of electrospun nanofibers. These scaffolds are studied and discussed using different polymers to show the effect on skin repair mechanisms and investigate the remodeling abilities aiming to potentially show a foundation for clinical applications and industrial manufacturing. The extracellular matrix (ECM) and the nanofiber structure share many similarities, and the use of different types of polymers, including biopolymers like collagen and chitosan and biodegradable polymers like polycaprolactone, polylactic acid, and polyvinyl alcohol, helps to make the field relevant to skin regeneration and remodeling. Hence, this review summarized and discussed the polymeric nanofibers such as collagen, polycaprolactone, poly vinyl alcohol reporting pre-clinical trials of wound healing and skin regeneration.

1. Introduction

The skin is considered the largest organ in the human body that is functionalized to protect the human systems against mechanical, chemical, and thermal stress, microbial/pathogenic invasion, and prevent dehydration. Accordingly, the large surface area of the skin can be associated with several conditions such as cutaneous wounds of acute or pathological conditions which represent significant challenges clinically and socioeconomically. It has been statistically proven in the year 2003 that globally over 6 million patients suffer from severe skin burns each year and among which more than 300,000 patients lose their fight against burn pain and pass away ultimately [1, 2, 3, 4]. It has globally shown an economic burden of over 9.5 billion US dollars a year [5, 6]. Wound healing delay or impairment is considered a global health issue with affects people suffering from comorbid diseases such as diabetes, cardiovascular diseases, cancer, and obesity. Non-healing wounds have shown negative impacts on patients’ life that includes different aspects from the quality of life, pain, and well-being psychological distress to physical discomfort [5, 7, 8]. As reported in 2014, 6.0% of the United Kingdom and 9.3% of the United States populations were diagnosed with diabetes which will indicate a global rise of diabetic adults to 439 million by 2030 [5, 6, 9]. This is related to the hospitalizations of diabetic foot ulcers, infection complications, amputations, and mortality of patients [6, 9]. Thus as a result of wounds with diabetes and obesity, the incidence of pressure and venous ulcerations is expected to rise in the upcoming years as a consequence of the aging of the population that is estimated to increase up to 60% in Europe population will be aged above 65 by 2050 and obesity that will exceed 20% of obese world’s adults by 2030 [5, 6, 9, 10]. Hemostasis, inflammation, proliferation, and remodeling are the four distinct but overlapping stages of the multistage biological process of wound healing. A proper biomaterial must be created to support the intricate skin architecture. The synthetic biomaterial scaffold must resemble the ECM and be resilient to the biological, topographical, and physicochemical characteristics of natural skin tissue [11]. As a result, traditional therapies for wound management have been urged for the need for advanced and more effective strategies to control the wound status, preventing invasive solutions to save the patients [8]. The era of biomaterial technology that has been rapidly developing recently has shown huge potential for clinical application including skin remodeling, tissue engineering, and wound healing. A large number of excellent biomaterials either naturally or synthetically have shown various advantages over traditional therapies [4, 8, 12, 13]. Mainly biomaterials include PLA, PCL, PVA, PEG, PEO, collagen, hyaluronic acid, sodium alginate, chitosan, gelatin, etc. [1, 2, 3, 4, 7, 8, 10, 13, 14, 15,]. Electrospinning and nanofibers formation have been the subject of intensive studies and research in multiple fields among is tissue-engineering. This is correlated to the large surface area to volume ratio and the high porosity of the nanofibers formed web [4, 8, 14, 15, 16,]. Thus, the biomedical application of nanofibers in wound care contributes not only to the physical protection of wound sites from infection and pathogenic sources due to the properties of high surface area and porosity of nanofibers but also provides an excellent environment for soft tissue regeneration and skin remodeling due to the nature of several biodegradable polymers which modulate the gaseous exchange of the wound location and help in promoting hemostasis while also preventing the scar formation of the skin [ 4, 8, 10, 12, 13, 14, 16].

In this study, we have reported several materials that have been used to produce electrospun nanofibers scaffolds. These scaffolds are studied and discussed using different polymer-nanofibers scaffolds to show the effect on skin repair mechanisms and investigate the remodeling abilities aiming to potentially show a foundation for clinical applications and industrial manufacturing.

2. Tissue scaffold and drug delivery

The unique properties of nanofibers from high surface area and wide porosity helped in the application of nanofibers in mechanical engineering and biological tissue scaffolds. Thus, the selection of the tissue scaffolding material is carefully selected to guarantee the biocompatibility of the human cells with it. The material properties have shown great influence on the biocompatibility of the surface chemistry of the scaffolds [13, 17, 18]. The mechanical support of the skin is regulated by several things rising from biological signals of growth factors, ECM, and the surrounding cells [17, 18, 19]. The responsible cells and growth factors vary from primary and secondary elements of ECM, among which are collagen, and natural polymers of different types: Types I and III which are considered primary structural elements of ECM that functionalized in supporting the tissue reconstruction [19]. The high surface area to volume ratio that nanofibers excel in, helps in the cell attachment which provides a regenerative tissue scaffold [17, 18, 19, 20, 21]. The natural ECM and its dimensional have been adapted to perform the scaffold of bioengineered polymers in the same manner. The variability of biodegradable polymers such as PLGA, PCL, etc.… are commonly used in electrospinning tissue engineering as they tend to produce highly structured tissue scaffolds with high porosity of both pore diameter and pore volume [4, 11, 17, 18, 19, 20, 22].

The electrospun nanofiber scaffolds that tend to have high porosity ease the passage of nutrient intake and metabolic exchange as the space provided for the cell to accommodate these activities is enough. For the use of electrospun nanofibers as tissue scaffolds, mechanical characteristics such as the modulus of elasticity and strain at failure are crucial. By altering the solution concentration and fiber orientation, the material characteristics may be appropriately tailored [4, 11, 13, 20, 21, 23]. In a study carried out by Matthews and his team where they investigated the usage of Collagen Type I from calfskin and Types I and III from the human placenta to produce electrospun nanofibers. Results have shown that the electrospun collagen fibrils were tightly resembling the natural polymer tissue properties of both structural and biological. These electrospun collagen microfibrils allowed the cultivation of aortic muscle cells, which resulted in scaffolds with a high density of smooth muscle cells. The investigation has proven that the electrospun collagen revealed the presence of highly interwoven muscle cells [17, 21]. In another study, Huang and his team constructed an experiment on electrospun nanofibers of collagen and PEO mats to show their potentiality in wound healing and tissue engineering. The result was the production of uniform fibers with diameters between 100 and 150 nm. The significant intermolecular contact between the PEO and collagen component was assumed due to the better mechanical characteristics of the collagen nanofibers [17, 23].

Nanofiber mats are used as drug carriers in drug delivery systems, due to their great functional qualities. With biocompatible delivery matrices made of either biodegradable or nonbiodegradable polymers, controlled drug delivery at a set rate throughout a predetermined treatment time is conceivable [17, 22]. In a study carried out by Kenawy and his team investigating the potential of electrospun polymers PEVA, PLA with ethanol, and tetracycline hydrochloride as a drug delivery system. The results have shown that the release of tetracycline from electrospun fibers was much greater than from the casted films. The observations of electrospun PEVA AND 50/50 PLA/PEVA fibers have shown a very consistent release of tetracycline over the investigated period of 5 days [17, 22]. The previously stated studies have shown the necessity of applying nanofibers mats in controlled DDS and biomedical sectors. When administered to the skin, these medications with nanofiber as demonstrated in Figure 1, the incorporation can promote wound healing or just simple drug release for systemic or local therapeutic activity.

Figure 1.

Schematic illustrating various types of pharmaceutical agents that can be incorporated into nanofibers for wound dressings.

2.1 Nanofibers scaffolding for wound healing

Scaffolds may be easily modified in situ during the electrospinning process or thereafter to be suited for a particular biomedical application with the usage of electrospinning [13, 24]. The choice of polymer, which determines the mat’s rate of degradation, can be used to influence the rate at which a drug or drugs are released from a nanofiber mat or the positioning of the drug within or on the surface of the fibers [4, 13, 22, 24, 25]. Information on choosing a polymer is supplied, along with several strategies for customizing the active agent’s position inside the electrospun mat [11, 13, 24]. Rapid hemostasis and effective antibacterial properties are the two key criteria for acceptable present-day wound dressings. The goal of a wound dressing is to quickly achieve hemostasis, and it should also have powerful antibacterial properties in order to protect against bacterial infections from the surroundings. Due of its flexibility in creating nanofibrous membranes for wound dressing that can provide a moist environment surrounding the wound region that promotes healing, electrospinning has gained an enormous amount of interest [4, 13, 24, 26].

2.1.1 Selection of polymers to enhance wound healing mechanisms

The suitable polymer matrix, whether natural, synthetic, or a combined mix of polymers, should be used when developing nanofiber mats for wound healing applications in order to meet the necessary scaffold qualities. Utilizing nanofiber-based systems, several natural and synthetic chemicals have recently been tested for their ability to improve and enhance the healing of wounds [24, 27]. Among the most investigated electrospun nanofibers is an organic based polymer, PCL because it supports faster healing and decreases inflammatory infiltration, PCL, a biodegradable and biocompatible poly(a-ester), has been extensively studied and used for tissue regeneration and wound healing applications. PCL is a useful matrix for loading natural compounds like curcumin, herbal extracts, and proteins because of its significant physico-chemical features, including hydrophobic qualities, great spinnability, favorable mechanical properties, and delayed degradation [10, 14, 28]. Several studies have investigated PCL nanofibers alone and drug loaded. Thus, in a study conducted in 2015 by Ana Delia Pinzon-Garcia and her team investigating Bixin-loaded PCL nanofibers, as PCL has tendency of incorporating the insoluble medications and may be employed in a variety of formulations for controlled drug administration and tissue engineering. The study noticed that animals treated with Bix-PCL1 nanofiber and Bix-PCL2 nanofiber showed a much higher percentage of wound closure. According to their finding, even while Bixin release from PCL nanofibers promoted wound healing from the first days on and was more effective than PCL alone, increasing Bixin concentration on PCL’s more hydrophobic nanofibers created an unfavorable environment for wound healing. Here, they showed that the most effective concentration of Bixin in the nanofibers to induce an efficient rapid wound closure was 2.5% [24, 28]. In another study, Sang-Myung Jung and his team investigated the natural extract of Spirulina loaded with electrospun PCL nanofibers on animal model. The in vivo testing showed how the nanofiber affected skin, which reacted intricately with different substances. The team applied the Spirulina extract PCL nanofibers directly to the full thickness wound and assessed its effects, which showed a fast reduction in the size of the lesion. In particular, the average size of the groups varied starting on day 5 and persisted until day 10. These outcomes proved that spirulina extract-PCL nanofibers had the same effects in vivo as it did in vitro [29]. In a further studied PCL-loaded nanofiber Robin and his Indian team, investigated the capacity of ZnO nanoparticles to produce ROS, which may have a function in biological systems, is well established. Through growth factor-mediated pathways, ROS can promote cell adhesion and migration to speed up wound healing. Hence, the study has discussed the creation of ZnO nanoparticle-infused electrospun PCL scaffolds and their potential to serve as materials that can replace skin and speed up the healing process. In guinea pigs, subcutaneously implanted PCL membranes with or without ZnO nanoparticles were tested. Studies in immunology, macroscopy, and histology have demonstrated that using membranes containing ZnO nanoparticles improves cell adhesion and migration. The membranes with implanted ZnO nanoparticles do not exhibit any adverse reactions of irritation. The implant also improved wound healing without the development of scars [30].

Other highly studies polymer is PLA, that is selected in various studies as the supporting material because it is biodegradable, biocompatible, and can support the proliferation and attachment of various cells promoting the healing process of the skin. It is possible to employ the patterned PLA surfaces as a platform for the targeted transport and engraftment of different type of cells such as stem cells [31, 32, 33, 34]. In a study investigated the usage of PLA with other nanofibrous scaffolds by Marziyeh Ranjbar-Mohammadi’s team, the design of electrospun composite nanofibers using natural nano-fibrillated chitosan /ZnO nanoparticles combination as the nanofiller ingredient has been examined during this study. The key components are PLA and K/PVA. K/PVA/Chitosan ZnO (2:1)-PLA/Chitosan ZnO (2:1) nanofiber, with a diameter of 352.50 ± 31 nm, a contact angle of 48 ± 3°, and a tensile strength of 0.96, 0.18 MPa, is proposed as a suitable wound healing scaffold with the greatest antibacterial and ability to enhance cell proliferation [31]. Additionally, as PLA nanofibers are biocompatible and have a large specific surface area and high porosity, they were employed in the study carried out by Thuy Thi Thu Nguyen’s team to study the PLA as a carrier for Cur to improve its functional characteristics. Cur/PLA blended nanofibers with various concentrations of Cur were studied for their chemical and biological properties. Cell adhesion and proliferation are promoted by the inclusion of Cur in the blended nanofibers, even at concentrations as low as 0.125 weight percent. A mouse model was used to test the in vivo wound healing capabilities of Cur-loaded PLA nanofibers. When compared to PLA nanofibers (58%), treatment with Cur-loaded PLA nanofibers dramatically enhanced the rate of wound closure (87%) on day 7. The findings of this study indicate that Cur-loaded nanofibers have shown no adverse actions and increased the potential of using PLA loaded curcumin in wound healing patches [32]. In another study conducted in Italy by Giulia Milanesi, electrospun PLA and essential oil nanofibers were then covered with medium-molecular-weight chitosan to enhance the antibacterial effect of EO. Before electrospinning, BP-EO or L, both of which are known for having antibacterial properties, were added to the PLA/acetone solution. The results showed that the CS coating improved the fibrous mats’ hydrophilicity, increased EO’s antibacterial potential, and encouraged cell adhesion and proliferation [35]. Also, in a study carried out in 2015 in Prague, Czech Republic on AA-collagen poly lactic acid nanofiber scaffold investigating how human dermal fibroblast adhesion and proliferation were affected by fibrin placed on a nanofibrous membrane and AA added to the cell culture medium. The study findings demonstrated that compared to the membrane lacking fibrin, fibrin deposition led to noticeably better cell adherence and spreading. While the cells on the membranes with fibrin were polygonal in form and widely dispersed with well-developed characteristic FA carrying 1-integrins, the cells on the membranes without fibrin were spherical until the third day of cell culture. The adherence of fibroblasts to fibrin molecules is mediated by 1-integrins, namely 51 integrins (together with v3 and v3 integrins), in which these adhesion receptors recognize the RGD motifs. The collagen receptors 11, 21, and 31 integrins are also members of the group of integrins to fibrin-coated membranes, particularly in the medium with AA, collagen expression and synthesis increased, which may have contributed to the enhanced cell adhesion to the modified PLA membranes. Additionally, the fibrin pulls molecules of ECM from the cell culture media through its C domain, including fibronectin and vitronectin, which help to enhance cell attachment even more. Cell adhesion on unaltered membranes is essentially solely mediated by spontaneously adsorbed ECM molecules from the cell culture medium or by cell deposition on the membrane surface. Additionally, these compounds could be adsorbed insufficiently and with the incorrect spatial configuration for cell adhesion receptor recognition. The research demonstrated that AA boosted collagen I expression and induced cells to deposit collagen fibers on material surfaces. The cells grown in a typical cell culture media (without AA) did not significantly develop collagen ECM on the surface of the material. Collagen I was expressed more strongly by the cells grown in the regular culturing medium on membranes coated with fibrin than by the cells grown in the medium with AA on membranes without coating. On the material surface, however, these cells did not significantly deposit a fibrous collagen matrix. The study had proven that human dermal fibroblasts were significantly impacted by the fibrin nanocoating on PLA nanofibrous membranes. Fibrin boosted the expression of 1-integrins, cell proliferation, and collagen production while promoting cell adhesion and spreading. Fibrin likely had a positive impact on cell adhesion and proliferation because of its simplicity in binding to cells via integrin adhesion receptors, which attracted sticky molecules from the cell culture media. It was possibly also because of the cells’ mitogenic properties. Collagen I’s mRNA expression, the total amount of collagen produced, and its deposition as ECM on the membrane surface were all boosted by fibrin [11, 36].

Further, the well-known PVA is a synthetic polymer that is water soluble, non-toxic, biocompatible, and biodegradable. PVA has so received much research in the domains of biomedicine, polymers, and textiles. PVA resins offer a wide range of practical uses due to their outstanding chemical resistance, physical characteristics, and biocompatibility, including fibers for clothing and industry, adhesives and binders, films, membranes, materials for drug delivery systems, and embolic materials that destroy cancer cells. Due to the use of water-based solvents, PVA electrospinning has been the subject of much research. PVA was therefore selected as an appropriate foundation polymer to create an electrospun nanofibrous structure [37, 38, 39, 40, 41, 42]. In a study conducted in 2020 in Iran investigating the PVA nanofibers anti-bacterial efficacy when loaded with anti-biotic drug, the study’s primary objective was to create wound dressings utilizing the electrospinning technique and a mixture of TXA and PVA to examine the blood coagulation capabilities. Additionally, CTX and PVA were blended to take into account their antibacterial capabilities. The findings of a study on the antibacterial activities of Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria showed that the antibacterial characteristics grew stronger with rising MIC. 100% was achieved in PVA/CTX dressing with MIC: 8 g/ml. PVA-TXA dressings (10 mg/ml) and (20 mg/ml) both showed adequate blood coagulation abilities. PVA-TXA (20 mg/ml) exhibited a stronger blood coagulation ability with an average absorption of 0.031. The results have proven the ability of PVA nanofibers to enhance the wound healing mechanism specially when loaded with certain concentrations of TXA and CTX [37]. Herein, in another study by Sama Ghalei and her team, a new nanocomposite wound dressing was created implementing electrospun PVA nanofibers and nanoparticles that can release the medication DLF at the wound site. They said that because the structure combines the beneficial qualities of both polymeric nanofibers and NPs, it is extremely promising. Due to the drug-loaded NPs’ insoluble nature in the original PVA solution, the hydrophilic PVA nanofibers may also be used to load and release the hydrophobic DLF. The electrospun composite dressing made of zein nanoparticles and PVA nanofibers has a tremendous potential for use in the treatment of wounds, according to the results [43]. Also, in a study conducted in early 2012, electrospinning was used to create CS aqueous salt combined with PVA nanofiber mats. Without using harmful or toxic solvents, CS was dissolved in distilled water along with HOBt, TPP, and EDTA. In an in vivo wound healing test, the CS-HOBt/PVA and CS-EDTA/PVA nanofiber mats showed satisfactory antibacterial activity against both gram-positive and gram-negative bacteria, and the CS-EDTA/PVA nanofiber mats outperformed gauze in reducing acute wound size in the first week following tissue damage. The study has suggested the significance of the CS-EDTA/PVA nanofiber mats to be used as wound dressing materials since they are biodegradable, biocompatible, and antibacterial [44].

Moving forward to natural based polymers, starting with one of the most prevalent natural polysaccharides is chitosan, a partly N-deacetylated derivative of chitin. Chitosan is the only naturally occurring alkaline polysaccharide with positive charge that has been identified so far. It is made up of random mixes of -(1-4)-linked d-glucosamine and N-acetyl-d-glucosamine in the polymer backbone. Due to its excellent biocompatibility, biodegradability, antibacterial, and anti-inflammatory properties, chitosan-based biomaterials have attracted considerable attention recently. After cellulose, chitosan is the most prevalent biopolymer on earth. Shrimp and other crustacean shells are used to extract chitosan. There have been reports of other extraction techniques, however the deacetylation of chitin is the most often used. As a biopolymer, chitosan has several functions and applications. However, altering its chemical structures can improve its mechanical, chemical, and biological properties [45, 46, 47, 48]. In a study carried out in 2009 on chitosan combined with silver nanoparticles. The study investigated the electrospinning CS/PEO solutions containing Ag/CS colloids with in-situ chemical reduction of Ag ions, fairly homogeneous CS/PEO ultrafine fibers containing silver nanoparticles were effectively created. The research demonstrated the efficacy of CS/PEO and Ag/CS/PEO nanofibers with a 1:1 mass ratio of CS/PEO against E. coli. The antibacterial activity of the nanofibers containing Ag nanoparticles was superior to that of the CS/PEO nanofibers. For Ag/CS/PEO nanofibers containing 1.1 and 2.2 wt% nanoparticles, respectively, all bacteria were inactivated within 10 and 6 hours. Ag/CS/PEO membranes have shown extremely potent antibacterial properties that might be employed in a variety of biomedical applications, including tissue scaffolds, body wall repairs, wound dressings, and antimicrobial filters [49]. Additionally, in an interesting study that as conducted on natural extracts in order to create a biocompatible, antibacterial nanofibrous wound dressing, two natural extracts were loaded onto synthetic honey, PVA, and chitosan nanofibers. The HPCS nanofibers in the HPCS-CE, HPCS-AE, and HPCS-AE/CE nanofiber mats, respectively, were loaded with dried aqueous extract of Cleome droserifolia (CE) and dried aqueous extract of Allium sativum (AE). By demonstrating improved wound closure rates in mice and by histologically examining the wounds, a preliminary in vivo result found that the produced nanofiber mats improved the wound healing process when compared to the untreated control. Additionally, the HPCS and HPCS-AE/CE showed similar effects on the wound healing process when compared to the commercial dressing the study referred to, however the HPCS/AE allowed for a faster rate of wound closure. Results of studies on cell cultures demonstrated that the created nanofiber mats were more biocompatible than the commercial product the study referred to, which displayed pronounced cytotoxicity. The study significantly proven that the natural nanofiber mats that have been produced have an opportunity to be effective, biocompatible, antibacterial wound dressings [50]. Consequently, the other natural polymer that is extensively studied in the wound-care management is collagen, an attractive polymer for the creation of wound dressings since it is a biopolymer and a significant component of ECM. These include minimal immunogenicity, strong biocompatibility, hemostatic qualities, the capacity to stimulate cellular proliferation and adhesion, non-toxicity, and low antigenicity. The ECM of various sensitive tissues is mostly made up of collagen. All dermal dry materials, which are located at the skin’s level in proportions of 70–80 percent, define the presence of collagen. Collagen promotes the maintenance and differentiation of cellular phenotypes, hence interactions between collagen and cells are crucial for the process of wound healing. Collagen-based nanofibers have also showed intriguing features that are useful in the fields of skin regeneration and wound dressings [51, 52, 53]. In a research study conducted by Cheng-Hung Lee ‘s team investigating the capabilities of Collagen nanofibers in diabetic wounds. The team produced nanofibrous collagen/PLGA scaffold membranes, which allowed for the sustained release of Glucophage for diabetic wounds. The development of glucophage-loaded collagen/PLGA nanofibrous membranes that sustainably provided medication to treat diabetic wounds. For more than 3 weeks, the team has proven that the nanofibrous membranes emitted significant amounts of glucophage. In their finding, they have stated that the collagen/PLGA membranes coated with glucophage significantly accelerated the healing of diabetic lesions. Additionally, due to the downregulation of matrix metalloproteinase 9, the collagen content of diabetic rats employing drug-eluting membranes was greater than that of the control rats. According to the experimental findings presented by the team, glucophage-loaded collagen/PLGA membranes with a nanofibrous structure were proved successful in promoting early wound healing in diabetic wounds and increasing collagen content [51, 54].

3. Conclusion

Due to its ease of use and ability to be combined with other techniques, electrospinning, while being a rather old process, has maintained its significance. Electrospinning, which is the most reliable size for native ECM, allows material characteristics to be controlled down to the nanoscale level. The approach to building nanofiber scaffolds from a single polymer, many mixed polymers, or various inputs may be adapted with the help of changes in the electrospinning equipment and process parameters. Due to the development of novel polymers and manufacturing techniques, multifunctional wound dressing scaffold materials with adaptable surface functions and exceptional structural and mechanical characteristics are now feasible. Bio-based polymeric materials have frequently been advocated for skin tissue regeneration in a variety of wound healing settings as useable skin substitutes, useful dressings, and wound healing patches. As many functional biomaterials, superabsorbent dressings, multifunctional wound dressings, and skin tissue scaffold materials are launched in place of traditional gauzes, the need for bioinspired wound care solutions is growing. Potential wound care solutions will need to offer a variety of unique biological capabilities, such as biomimetic, bio-responsive, antibacterial, and hemostatic qualities, to establish a favorable microenvironment. The anticipated efficacy in wound healing scaffolds will be closer to reality as more current biopolymers are studied for their physicochemical, biological, and mechanical characteristics, as well as when new ones are created. Studies employing nanofibers for tissue engineering purposes have multiplied exponentially to date. This paper mainly discussed the most recent advancements employing different skin-remodeling polymers for wound healing and skin regeneration. Numerous research has shown that natural bio-macromolecules are legitimate substitutes for their synthetic equivalents when it comes to wound treatment, as was covered in this review. More intriguingly, the ability to electrospun fibers into nanostructures by applying nano-structuring enables the development of biomimetic dressings with enhanced bioactivity for stimulating tissue regeneration. Different wound models have been used in in vitro and in vivo testing to demonstrate the effectiveness of electrospun dressings made of natural/synthetic polymeric materials in promoting cell migration and proliferation, speeding wound closure, regulating the inflammatory response, and, in certain circumstances, avoiding the formation of biofilms. However, difficulties in electrospinning some materials are related to the following: choosing the proper solvents or polymer additives to facilitate fiber extrusion; the requirement of postprocessing procedures to improve the mechanical resistance and control the scaffolds’ rate of degradation. Importantly, in terms of fiber shape and dimensionality, the scaffold’s design is biomimetic for the natural ECM, and its likely functions as an immediate short-term matrix for hemostatic activities and skin remodeling cells that assist wound healing. Electrospun nanofiber scaffolds have shown to be very adaptable. The interactions that took place at the interface between the materials’ surface and biology may be controlled by adjusting the matrix chemistry, surface functionality, and mat degradation rate in combination. Natural, semi-synthetic, and completely synthetic polymer-based nanofibers and their composites have demonstrated promise as materials for skin regeneration and scaffolding for wound healing. Nanofiber scaffolds have a position in wound care therapy because they resemble natural ECM shape and structure both on their own and when combined with other functional polymers. This provides a good environment (niche) for skin tissue rebuilding. Systematic investigations are also required to standardize fabrication techniques under hygienic electrospun settings to gradually transition nanofibers from the laboratory to the commercial scale. As previously discussed throughout the review, tissue regeneration and skin remodeling are subjective to the degree of stress/wound and the causes of such injuries which result in the selection of a certain polymer whether natural or synthetic source that can itself act as ECM or can be loaded with various substances such as antibiotics, hemostatic agents, growth factors, antioxidants, and anti-inflammatory. As a result, the nanofiber mat may be employed as an effective skin substitute material that will accelerate cell migration and proliferation to heal wounds quickly. The review suggests carrying out more clinical investigations while considering the patient acceptability of the administration form to improve the incorporation of appealing medications into nanofibers and using a combination of various biopolymers. The challenge of scaling up to mass manufactures of polymeric or drug-loaded electrospun mats must also be taken into account.

Acknowledgments

This work is supported by the research and development department of Eva Pharma. The author acknowledges support from the director of the department Laila Gad ElRub and the manager of the transdermal and patches sector Bassem Samy Shenouda. The author is grateful for their guidance, ongoing discussions, critical suggestions, and knowledge in the era of biomaterials. My apologies to all the investigators, researchers, and scientists in the area whose publications were not cited in this overview. This can only be a small sample of the many excellent works that are accessible in the literature.

Conflict of interest

The author declares no potential conflicts of interest with respect to the research and/or publication of this work.

Notes/thanks/other declarations

Thanks to my beloved parents Hatem ElGamal and Lilian Ibrahim for their continual love and support.

Acronyms and abbreviations

ECM	Extracellular matrix
PLA	Polylactic acid
PCL	Poly caprolactone
PVA	Poly vinyl alcohol
PEG	Poly ethylene glycol
PEO	Poly ethylene oxide
PLGA	Poly lactic-glycolic acid
PEVA	Poly ethylene co-vinyl acetate
DDS	Drug Delivery System
Bix-PCL	Bixin-loaded PCL
ZnO	Zinc Oxide
ROS	Reactive oxygen species
K	Keratin
nm	Nanometer
MPa	Mega Pascal
Cur	Curcumin
EO	Essential oil
AA	Ascorbic acid
CS	Chitosan
BP-EO	Black pepper-essential oil
L	Limonene
TXA	Tranexamic acid
CTX	Ceftriaxone
DLF	Diclofenac
NPs	Nanoparticles
HOBt	Hydroxybenzotriazole
TPP	Thiamine pyrophosphate
EDTA	Ethylenediaminetetraacetic acid
Ag	Silver
HPCS	Synthetic-honey chitosan nanofibers
CE	Cleome droserifolia
AE	Allium sativum aqueous extract