Electrospun Nanofibers for Wound Management

Abstract

Electrospun nanofibers show great potential in biomedical applications. This mini review article traces the recent advances in electrospun nanofibers for wound management via various approaches. Initially, we provide a short note on the four phases of wound healing, including hemostasis, inflammation, proliferation, and remodeling. Then, we state how the nanofiber dressings can stop bleeding and reduce the pain. Following that, we discuss the delivery of therapeutics and cells using different types of nanofibers for enhancing cell migration, angiogenesis, and re-epithelialization, resulting in the promotion of wound healing. Finally, we present the conclusions and future perspectives regarding the use of electrospun nanofibers for wound management.

Graphical Abstract

In this mini review, we summarized the recent advances of electrospun nanofiber-based wound dressings to control the pain, hemorrhage, infection, cell migration, remodeling, and angiogenesis.

1. Introduction

Effective wound healing is one of the most desirable and impactful medical outcomes in the world. Generally, the wound healing process goes through several complex stages: hemostasis, inflammation, proliferation, and remodeling (Figure 1).^[1–3] Depending on healing time, wounds can be classified as acute and chronic. Acute wounds heal quickly, with healing times ranging from days to weeks, but chronic wounds can take months to years to heal completely.^[3] One particularly devastating class of non-healing wounds, diabetic ulcers, are severe, and their persistence consistently leads to invasive surgical procedures, amputations, and even death. An estimated 552 million people worldwide have diabetes, of which 25% may develop foot ulcers. Of the 25% of people with diabetes with foot ulcers, 60% may further develop infections, which increases the likelihood of amputation and mortality.^[4–6] Unlike non-healing wounds, acute wounds heal quickly through the rapid remodeling of skin tissues. However, burn and occupational injuries also present unique challenges for clinicians as they are often complex to treat and manage effectively.^[7]

Figure 1.

Stages of wound healing and their major cellular components. (A) Wound healing begins with hemostasis, where a platelet plug prevents blood loss, and a preliminary fibrin matrix is formed. (B) Inflammation then ensures to remove debris and prevent infection and starts with an influx of neutrophils, which is promoted by histamine release from mast cells. Monocytes arrive later and differentiate into tissue macrophages to clear remaining cell debris and neutrophils. (C) During the proliferative phase, keratinocytes migrate to close the wound gap, blood vessels reform through angiogenesis, and fibroblasts replace the initial fibrin clot with granulation tissue. (D) Finally, the deposited matrix is remodeled further by fibroblasts, blood vessels regress, and myofibroblasts cause overall wound contraction.

Local treatment with saline and common wound dressings may be effective treatment modalities for minor chronic wounds. To treat a sizeable chronic wound, developing innovative wound dressing materials with multiple therapeutics is necessary to facilitate wound healing progression while mitigating grafting, scar formation, and secondary surgical interventions.^[8] While considering wound dressing efficacy, we can categorize wound dressings based on their comprising materials.^[9,10] For example, (i) gauze sponges: these types of dressings are common for all wounds and made from 100% cotton.^[9] Gauze is adequate at absorbing exudate and other fluids. Moreover, gauze is readily available, easy to use, and affordable. (ii) Gauze bandage rolls: Similarly, these dressings are made from 100% cotton, which can be used as the first layer dressing or an additional protection layer. This type of dressing is suitable for a wound on the head, limb, and other complex wounds.^[8] (iii) Non-Adherent Pads: This type of dressings is generally used for wounds with moderate drainage. ^[9,10] Non-adherent pads are advantageous in this regard as they avoid sticking to the wound itself. (iv) Foam dressings: This type of dressings is composed of ultra-soft, highly absorbent foams and is widely used for medium to large-sized wounds with moderate to heavy exudate.^[9] Moreover, foam dressings act as force-shielding cushions and maintain healthy levels of moisture. (v) Calcium alginates: This type of dressings includes alginate elements, which are primarily used for moderate to heavily exudative wounds and arterial ulcers.^[8–10] This dressing shows a high absorption rate that can hold as much as 20 times its weight in moisture. (vi) Hydrogel dressings: This type of dressings is used for dry wounds, which can lend moisture to a wound and help to promote cell growth.^[9,10] (vii) Transparent dressings: This type of dressings is composed of transparent materials, which allow the transfer of moisture while allowing visualization of the wound.^[9,10] When selecting a suitable wound dressing, one must address questions like (i) What type of wound is it?, (ii) What does the surrounding tissue look like?, (iii) What do the edges of the wound look like?, and (iv) How much, if any, drainage is there? This kind of assessment helps determine which stage of the healing process the wound is in and which wound dressing is ideal for improving healing outcomes.^[8–10]

Regardless of the wound dressing, wounds progress through the wound healing cascade, which includes four different coordinating phases: hemostasis, inflammation, proliferation, and remodeling (Figure 1).^[1–3] After an injury, hemostasis is initiated by platelets through the formation of a fibrin clot. The inflammatory phase is then activated by an influx of neutrophils and subsequently macrophages and lymphocytes.^[11,12] In the proliferative stage, new blood vessels form, and the synthesis of a new extracellular matrix (ECM) to promote re-epithelialization occurs. Typically, the duration of the healing process lasts several days to more than two years from the time of injury and varies based on the type of wound. Hemostasis begins with the localization of blood components to the endothelial layers of the vessel wall following injury (Figure 1A).^[12] In this process, platelets played a key role from a hemostatic plug, coagulation, and complement cascades; then, in the next phase, the prothrombin is activated to form thrombin, which cleaves fibrinogen to generate fibrin. Along with platelets and the plasma fibronectin, fibrin forms the clot. The clot is served as a matrix to defend to avoid serious blood loss and microbial invasion. The clot releases chemo-attractants for inflammatory cells, activation factors for local fibroblasts and endothelial cells, and vasoconstrictors, such as chemokine (C-C motif) ligand 5 (CCL5), thrombin, transforming growth factor-b (TGF-b), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Moreover, it prevents the premature development of blood vessels. During this stage, the fibrin plays a significant role in the inflammatory process because the fibrin binds to integrin CD11b/CD18 on infiltrating monocytes and neutrophils. It also binds to fibroblast growth factor-2 (FGF-2) and VEGF. Then the macrophages and T Cells at this site trigger the inflammatory phase.^[13–16]

Figure 1B is a schematic representation of the inflammation process during wound healing. This stage involves the recruitment of neutrophils, macrophages, and lymphocytes.^[17,18] Here, neutrophils kill bacteria by secreting antimicrobial peptides and generating reactive oxygen species. In the absence of inflammatory facilitators, neutrophils fail to produce antimicrobial peptides, which may contribute to a slowed healing progression. In the next two to three days, the monocytes become large colonies, and the monocytes release certain chemokines at different stages of healing. Within the wound, monocytes differentiate into macrophages. Macrophages help remove apoptotic neutrophils and other dead cells, function as antigen‑presenting cells, secrete cytokines, and release multiple peptide growth factors. Phagocytosis of apoptotic neutrophils by macrophages leads to the removal of chemokines from the area of inflammation and prevents further leukocyte influx.^[17,18] Several cytokines and growth factors are known to be secreted by macrophages. Such growth factors include TGF‑β, TGF‑α, basic FGF (bFGF), VEGF, and PDGF. These growth factors attract local endothelial cells, fibroblasts, and keratinocytes and facilitate wound healing by enabling cell proliferation, ECM deposition, and angiogenesis. However, inflammation seems not essential for skin wound healing as Martin et al. showed that the PU.1 null mouse, which is devoid of both macrophages and neutrophils, healed both incisional and excisional wounds at similar rates to wild‑type littermates but without scar formation.^[19]

The proliferative phase (Figure 1C) during wound healing typically starts around two days after injury and may last up to three weeks in a cutaneous wound.^[20,21] This phase overlaps with the inflammatory phase and begins with the degradation of the initial fibrin‑platelet matrix and subsequent invasion of fibroblasts and endothelial cells. The major events of this phase include the influx of fibroblasts, ECM deposition, formation of new blood vessels, and re‑epithelialization.^[20] The remodeling stages (Figure 1D) of wound tissue occur over a prolonged period that may last up to one year. Remodeling involves ECM turnover coupled with a significant decrease in cellularity. The decline in cellularity results from apoptosis of residual inflammatory cells and myofibroblasts as well as regression of the neovasculature. In humans, remodeling is characterized by both wound contraction and collagen remodeling.^[20,21]

The existing wound dressings are often limited to the incorporation of either one or two factors to elicit single or two functions (e.g., serving as a physical barrier, exudate absorption, stopping bleeding, pain relief, infection prevention, promotion of angiogenesis, acceleration of granulation tissue formation, and enhancement of reepithelialization). In contrast, electrospun nanofiber dressings can be incorporated with multiple factors to exhibit diverse functions. In addition, the mechanical properties of hydrogel dressings are relatively weaker compared to electrospun nanofiber dressings. ^[17–20] While comparing with other wound dressings, the nanofibrous wound dressings would be an appealing choice due to their biomimicry and the simple fabrication process.^{[22, 23]} The electrospinning process can form a nanofiber network, which mimics the architecture of natural extracellular matrix (ECM) for wound healing. Electrospun nanofiber materials can be processed into a wide range of shapes with different compositions, alignments, and morphologies. Electrospun nanofiber dressings can provide nanotopographic cues to guide cell migration, controlled pore sizes and porosities to enhance cell infiltration, and efficient delivery of therapeutics to prevent/treat infection, promote vascularization, granulation tissue formation and re-epithelialization, which results in the acceleration of wound healing. All these features make electrospun nanofiber-based wound dressings distinguishable as compared with other dressings.^{[22, 23]}

2. Control Hemorrhage

Bleeding is the initial outcome of most wounds, and the rate of bleeding depends on the size and complexity of the wound. Controlling the bleed is the initial step of any wound via suitable dressing. ^[24,25] Hemostasis, then, plays a vital role in controlling the hemorrhaging of a wound. Figure 2 represents the general mechanism of hemostatic plug formation during bleeding. ^[12] The details of plug formation were explained in the earlier section. While considering stopping bleeding, mechanical pressure (to press) is applied to initially treat a bleed. While gauze is commonly used to apply pressure to the wound, it may cause unnecessary blood loss, and in some cases, the gauze may adhere to the wound.^[26–28] Blood absorbed in the gauze forms a solid clot-gauze composite, which, when peeled away, often tears the wound and causes secondary bleeding and pain.^[29] While replacing the old wound dressing without causing secondary bleeds or hemorrhage will be difficult for extreme cases of hemophilic patients, where excessive bleeding occurs before coagulation. To circumvent these drawbacks, active clotting materials like chitosan have been widely used for rapid hemostasis.^[30] Recently, superhydrophobic or superhydrophilic materials have been employed for hemostatic purposes. For example, a superhydrophilic graphene sponge was used to absorb water from the blood, which quickly formed a dense layer of blood cells and platelets, thus promoting coagulation.^[29]

Figure 2.

Hemostatic plug formation in wound healing. Platelet activation cascade leads to hemostatic plug formation, and the coagulation cascade contributes to the stabilization of the thrombus. Adapted with permission from Ref. [12]. Copyright 2015 Elsevier.

Electrospun nanofibers have been widely used to control hemorrhage with and without the incorporation of clotting factors.^[26] For example, traditional electrospun nanofiber mats were regularly used as mechanically compressible wound dressings. For example, Giri Dev et al. reported electrospun PCL/starch blend nanofibers for rapid blood clotting in 156 s.^[31] Through simply blending with polymeric materials, hemostatic agents like tranexamic acid (TXA), estradiol, or thrombin incorporated wound dressings have been widely established in different wound management studies.^[26] Sasmal et al. demonstrated that TXA-incorporated chitosan nanofiber membranes showed both antibacterial and hemostatic properties.^[32] This membrane could be a potential candidate for wound dressings. To support this study, Varshosaz et al. demonstrated the TXA-loaded polyhydroxyethylmethacrylate, polyglycerol sebacic acid nanofibers for rapid hemostasis in rat tail cut wounds.^[33] To increase the efficiency of the wound dressing, dual drugs like TXA and Ceftriaxone (CTX)-loaded polyvinyl alcohol (PVA) nanofibers were developed to investigate both antibacterial and rapid blood clotting capabilities. PVA/CTX nanofiber dressings with MIC: 8 μg/ml reached 100% clotting efficiency. But PVA-TXA (10 mg/ml) and PVA-TXA (20 mg/ml) dressings demonstrated the acceptable ability of blood coagulation.^[34] In another study, Unnithan et al. demonstrated the use of Estradiol-loaded electrospun nanofibers for the post-menopausal wound dressing.^[35] Estradiol-loaded polyurethane (PU)-dextran nanofiber dressings showed enhanced blood clotting ability when compared with the estradiol deficient PU nanofiber dressing. Generally, calcium ions as the divalent metal ions have been widely found in the human body, especially in bone. Interestingly, calcium ions also make significance in blood clotting.^[36] For example, Park et al. reported that electrospun PCL nanofibers with the incorporation of chitosan and CaCO₃ improved blood coagulation. ^[36] Chitosan rendered both the antibacterial property and wettability in the wound for rapid healing, while the CaCO₃ inorganic particles promoted rapid blood clotting in the wound.

Recently, Xie and colleagues introduced a new concept using expandable nanofiber objects that can expand in situ and retain elasticity and super absorptivity. ^[37,38] The thrombin-immobilized nanofiber peanuts showed excellent hemostatic ability in a porcine liver injury model. Similarly, Mo et al. reported ultralight gelatin nanofiber sponges for hemostasis.^[39] The gelatin nanofiber sponge activates platelets in large quantities to promote the formation of the platelet embolism and simultaneously escalated the extrinsic and intrinsic coagulation pathways. In vivo studies using a rabbit ear artery injury model and a rabbit liver demonstrated the superior capability of the gelatin nanofiber sponge in forming stable blood clots in the shortest time with the least blood loss.^[39] Overall, the amphiphilicity of the nanofiber dressings and the incorporated clotting factors play significant roles in hemorrhage control. In addition to that Long’s research group has widely used electrospinning for the rapid hemostasis and antibacterial activity.^[40–44] They reported CuS composite nanofibers based onsite wound dressing using a portable electrospinning device.^[40] The CuS composite nanofibers can be deposited in situ onto the wound to simultaneously achieve rapid hemostasis outdoors and ablate superbacteria without requiring the use of other materials or devices. In another study, they have developed an in-situ electrospinning for minimally invasive surgery, demonstrating the nanofiber fabrication through laproscopic way into the organ.^[41] This laparoscopic electrospinning technique exhibited rapid hemostasis, less postoperative inflammatory responses, and faster recovery than traditional hemostasis method. Although studies have reported the tranexamic acid (TXA), Estradiol, or thrombin-like hemostatic agents incorporated nanofiber wound dressings for management of hemorrhage, there are still some shortcomings of electrospun nanofibers in hemostatic applications. The currently developed electrospun nanofiber dressings are mainly used for compressible hemorrhage rather than junctional and noncompressible hemorrhage. Apart from that, the morphology of the wound dressing also played a key role in the blood clotting. For example, Li et al. demonstrated that a nano-structured surface can achieve fast clotting with unique blood loss-free, unforced detachment from the wound site, and simultaneously reduced bacteria adhesion.²⁹ The nanostructured surface rendered by electrospun nanofibers was demonstrated to promote the activation, adhesion, and orientation of platelets.⁴⁵ Other than the surface topographies, 3D electrospun nanofiber matrices with high capability in absorption can concentrate the blood and promote coagulation, exhibiting a tamponade effect.²⁹ Therefore, clotting-promoting performance can be further enhanced by performing a parametric study of the surface topographical features, 3D structures, and chemical compositions. With these endeavors, the nanofiber material design strategy would lead to a more efficient hemostatic product for clinical use.

3. Prevent and Treat Infection

Generally, wound dressing materials composed with antimicrobial components. The antimicrobial properties can be generated in three ways: (i) in situ generation of antimicrobial peptide inside the wound, (ii) antimicrobial components incorporated dressing (iii) antimicrobial polymer based wound healing patches.^{[22, 23]} Innate immunity serves as the body’s first line of defense against infection during the wound healing.^{[46, 47]} For example, monocytes, macrophages, neutrophils, and epithelial cells can express and produce antimicrobial peptide LL-37 after incubation with 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) an immunomodulating compound or 1,25(OH)₂D₃ eluting biomaterials. ^{[48, 49]} This induction occurs only in humans and nonhuman primates because the vitamin D receptor response element (VDRE) is located on a retro-transposable Alu-element or short-interspersed nuclear element specific to primates.^[47–51] Recently, Xie and colleagues reported a variety of vitamin D₃ incorporated-nanofiber dressings for endogenous secretions of LL-37. ^[52–55] For example, Jiang et al. reported that vitamin D₃-loaded PCL fibers could induce the production of a significantly higher level of hCAP 18/LL-37 than the free drug.^[51] Figure 3A–D represents photographs and SEM images of 1,25(OH)₂D₃-loaded electrospun nanofibers and their LL-37 production in an ex vivo human skin model. This is notable given that LL-37, when produced by monocytes, is bactericidal and could prevent infection (Figure 3E–H). Xie group also developed vitamin D₃-loaded sutures for in situ antimicrobial peptide LL-37 production.^[53] Vitamin D₃ and pam3CSK4 peptides were co-delivered via nanofiber sutures over four weeks, which enhanced the induction of antimicrobial peptide LL-37 in monocytes and keratinocytes. In another study, Chen et al. evaluated endogenous antimicrobial peptide production of subcutaneously implanted 25-hydroxyvitamin D₃ (25(OH)D₃)-eluting radially-aligned PCL nanofiber scaffolds in human immune system-engrafted mice.^[55] In addition to overexpression of LL-37, the attenuation of inflammatory response was also noted.

Figure 3.

Endogenous antimicrobial peptide production using 1,25(OH)₂D₃-loaded PCL nanofiber membranes. (A) Photograph shows a 1,25(OH)₂D₃-loaded PCL fiber membrane with a diameter of 5 mm. (B-D) SEM images of PCL fibers, 1,25(OH)₂D₃-loaded PCL fibers and 1,25(OH)₂D₃-loaded PCL/pluronic F127 fibers. (E) An artificial wound (epidermal and partial dermal layer 1-mm thick) with a diameter of 8 mm was created in each skin explant (Ctr: without any treatment). (F) Dressings containing either 1,25(OH)₂D₃-loaded PCL fibers or vehicle (PCL fibers) were placed in the wound. (G) The appearance of the skin tissue and nanofiber dressing after five days of culture. (H) Quantification of hCAP18/LL-37 production by ELISA after treatment for 1, 3, and 5 days. Adapted with permission from Ref. [52]. Copyright 2015 Future Medicine Group.

To prevent microbial infections in wounds and at surgical sites, antimicrobial agents-eluting dressings may serve as an alternative. Yang et al. created Janus-type fiber materials using PVP and ethylcellulose in combination with ciprofloxacin and silver nanoparticles.^[56] The Janus-type dressing provided a burst release of ciprofloxacin within 30 min and a gradual release of silver nanoparticles over 72 h, which effectively inhibited bacterial growth in wounds. Despite a lack of cytotoxic evaluation, this dressing demonstrated a promising antibacterial effect. Jannesari et al. carried out a similar kind of antibiotic treatment with ciprofloxacin HCl (CipHCl) using poly(vinyl alcohol)/poly(vinyl acetate) (PVA/PVAc) 50:50 blend electrospun nanofiber dressings.^[57] Nanofibers in the PVA/PVAc mats had a nearly 60 nm lesser diameter in the presence of CipHCl compared to PVA/PVAc only. Relatively, a slow CipHCl release over 250 h from the PVA/PVAc 50:50 nanofiber mat was observed in vitro in pH 7.4 PBS. Wound dressing materials based on blend electrospun fibers composed of modified polybutylene adipate-co-terepthalate and gelatin (PBAT/gelatin) and doxycycline (DOX) also demonstrated potent antimicrobial effects against S. aureus and P. aeruginosa, as reported by Varshosaz et al.^[58] The DOX-PBAT/gelatin fibers functionalized with RCD peptide resulted in a decrease in the wound healing period. This study served as an example of blend electrospinning and covalent immobilization can work synergistically to improved wound healing outcomes.

Degradability of electrospun nanofiber dressings remain a concern in several cases, particularly when a degradable fiber mesh is desired for the fast-healing acute wounds. Faccendini et al. prepared lysosome-based degradable pullulan (PUL), chitosan (CH), and citric acid (CA) blended with hyaluronic acid (HA), chondroitin sodium sulfate (CS), and norfloxacin (N). Blend scaffolds showed the sustained release of norfloxacin over 3 days and the presence of CS with norfloxacin gave a synergistic effect in promoting proliferation of fibroblasts and provided an antimicrobial efficacy for 48 h against S. aureus and P. aeruginosa.^[59] Recently, Su et al. reported the topical delivery of antimicrobial peptides from electrospun nanofiber dressings to treat multidrug-resistant bacterial biofilms in diabetic wounds.^[60] Human cathelicidin peptide 17BIPHE2 was encapsulated in the core of Pluronic F-127/17BIPHE2-PCL core-shell nanofibers. The peptide/nanofiber dressings effectively eradicated methicillin-resistant Staphylococcus aureus (MRSA) biofilms when combined with debridement.^[60] In another study, Su et al. prepared a Janus-type antimicrobial dressing for biofilm treatment in a mouse type II diabetic wound model.^[61] The Janus-type dressing consists of electrospun nanofiber membranes and dissolvable microneedle arrays, which synergistically enable peptide delivery to both the inside and outside of biofilms. The Janus dressings eradicated MRSA biofilms in ex vivo human skin wounds and type II diabetic mouse wounds after daily treatment without surgical debridement. Additionally, these types of dressings can remove the Pseudomonas aeruginosa and MRSA dual-species biofilms in ex vivo human skin wounds. Most recently, Su et al. demonstrated the incorporation of multiple therapeutic agents with different antimicrobial actions to Janus-type dressings.^[62] Such dressings showed the capability in eradicating biofilms in wounds created on ex vivo human skin explants. As the therapeutic agents incorporated are currently in clinical use, the dressings showed great promise for translation into clinic.

Natural antimicrobial polymers have been widely used for the fabrication of antimicrobial patches via electrospinning.^{[22, 23]} The increasing resistance against classical antibiotics arises from the possibility of synergistically combining these materials and applying them in different physical forms (e.g., coatings, films, emulsions and fibers).^{[63, 64]} For example, Natural antimicrobial polymers derived nanofibers have been paid much attention due to the simple processing and economic benefit in a wide range of applications including wound dressing, tissue engineering, and drug delivery. Sometimes, natural antimicrobial polymers are difficult to electrospin into nanofibers. These polymers often blended with other synthetic polymers are electrospun into nanofibers. In addition to that chemically modified antimicrobial polymers have also been electrospun into nanofibers. For example, chitosan is a characteristically antimicrobial polymer extremely active against both gram-positive and gram-negative bacteria.^[65] It would be an excellent candidate for the production of antimicrobial nanofiber dressings. Nanofibers made of chitosan blended with synthetic polymers (e.g., polyethylene oxide, polyvinyl alcohol, polycaprolactone) have been demonstrated to exhibit the biocidal properties.^[66]

4. Relieve Pain

Pain caused by wounds is unpleasant for patients, yet a mostly unavoidable occurrence during wound healing.^[62] Effective pain management can positively affect both patients’ lives and wound healing progression.^[65] Today, the knowledge behind the pathophysiology of pain and its clinical management remains somewhat limited.^{[64, 65]} The inability to identify the appropriate factors causing wound pain makes it difficult to develop an effective plan of care. Wound pain typically occurs as either nociceptive pain or neuropathic pain.^[66] Nociceptive pain is the normal physiological response to a painful stimulus and serves as a biological function to warn of injury. Neuropathic pain is caused by dysfunction or damage in the nervous system. This is an immediate response wherein damaged nerves cause signals to travel in abnormal pathways. When patients present pain to their healthcare provider, it is classified into four types: background pain, breakthrough pain, procedural pain, and operative pain.^[62–66] To initially treat pain during wound management, a non-opioid pharmacological intervention is preferred.^[62] If pain is not controlled with conservative treatments, an opioid, such as codeine or tramadol is typically added as an adjuvant. ^{[61, 62]} When a patient does not respond to second-step medications, more potent oral narcotics may be necessary to control pain.[ ^[62–66]] However, analgesia can facilitate ambulation, which encourages wound healing and reduces the risk of complications like deep vein thrombosis, pulmonary complications, and pressure ulcers.^[67]

Analgesia occurs due to different mechanisms determined by the analgesics released from nanofiber dressings. For example, salicylates, capsaicin, menthol and camphor are the counterirritant class of topical analgesics which reduce pain by activating and then desensitizing epidermal nociceptors.^[68] Lidocaine a amide-type anesthetic provides local anesthesia by interruption of transduction and transmission of nerve impulses through blocking voltage-gated sodium channels responsive for propagation of action potentials.^[69] Diclofenac sodium a non-steroidal anti-inflammatory drug exerts its action via inhibition of prostaglandin synthesis by inhibiting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) with relative equipotency. ^[70] In contrast to other non-steroidal anti-inflammatory drugs, meloxicam has greater inhibitory activity against the inducible isoform of COX-2 than against the constitutive isoform (COX-1). ^[71] Fentanyl a potent synthetic opioid similar to morphine exerts its effect by acting as a high-affinity agonist on selective Mu-opioid receptors in the brain. ^[72] Gabapentin an anticonvulsant seems to influence voltage-dependent calcium ion channels at the postsynaptic dorsal horns, which may disturb the series of events that could cause the experience of a neuropathic pain. ^[73] To control pain during wound healing, analgesic-eluting nanofiber dressings are considered excellent candidates due to their high surface area, porosity and, site-specific delivery.^[74] For example, Grewal et al. reported a transmucosal PCL nanofiber patch to deliver diclofenac sodium to treat toothaches.^[75] Similarly, Shen et al. reported a Eudragit L 100–55 nanofiber membrane loaded with diclofenac sodium, which had sustained and pH-responsive drug release profiles.^[76] Analgesics should be released from minutes to hours within the wound for immediate pain relief. To achieve rapid release, Ngawhirunpat et al. reported an electrospun PVA nanofiber mat loaded with meloxicam as a transdermal drug delivery system.^[77] Meloxicam is a drug used for controlling pain and inflammation in rheumatic diseases but is water-insoluble and has low dissolution rates and skin permeability. Their results revealed that the skin permeation flux of meloxicam delivered from the PVA nanofiber mat significantly increased. In the past few decades, analgesic-loaded wound dressing has been getting much attention. Particularly, nanofiber dressings with analgesics have demonstrated substantial improvements in therapeutic efficacy. For example, TuneCoat™ a nanofiber-based dressing is designed to provide controlled localized delivery of analgesics, particularly for burn pain and peripheral neuropathies.^[78] The dressings rely on the unique behavior of nanofibers to provide controllable drug release in an easy-to-use, breathable, flexible dressing. The release kinetics of analgesics from electrospun nanofibers are mainly determined by hydrophilicity of drugs (dissolution), degradation rate of fibers, diffusion rate of drugs in nanofibers, desorption rate of drugs from nanofibers. Different approaches can be applied to prolong the release. For example, a more hydrophobic polymer as raw materials for electrospun nanofibers serving as drug carriers can slow down the penetration of water and release rates. Alternatively, analgesics can be loaded to the core of electrospun nanofibers using co-axial electrospinning. The increased shell thickness can serve as a diffusion barrier to delay the release of analgesics. Similarly, the surface of electrospun nanofibers consisting of analgesics blended with polymers can be coated with another polymer using in situ polymerization to achieve a long-term sustained release.^[79] For instance, the combination of different polymer fiber degradation rates enabled sequential release of opioids from PLGA (50:50) nanofibers initially followed by ibuprofen from PLGA (75:25).^[74–77]

5. Promote Healing

Since skin is present in the outermost layer of the human body, it is prone to injuries. ^{[79, 80]} There have been numerous attempts to medicate or cure these kinds of injuries, including wound dressing protocols, skin grafting, therapeutic drug delivery, and skincare products.^[76] In this section, we highlight efficacious therapies for wound healing. Delivery of therapeutics is supposed to ensure the release of bioactive molecules (e.g., growth factors, genes, and drugs) over a therapeutic time frame for maximum efficacy and bioactivity.^[81]

When designing drug delivery systems, it is vital to consider the release profile needs for a particular application. Drug release profiles from electrospun nanofibers can have both burst and gradual release profiles based on the technique used to load the drugs.^[82] For wound management and regenerative studies, both fast and gradual release of the drugs from the scaffold system may be necessary based on the stage of wound healing.^[83] Figure 4A represents the different fabrication techniques for incorporation of biomolecules or drugs to electrospun nanofibers, which can be classified into several categories: a) physical adsorption, b) blend electrospinning, c) co-axial electrospinning, and d) covalent immobilization. In the case of physical adsorption, biomolecules or drugs are adsorbed onto the electrospun nanofibers either from pure solution or emulsions. Blend electrospinning involves blending a mixture of biomolecules or drugs with the polymer solution prior to electrospinning.^[84] There may be the addition of stabilizing agents during or post-electrospinning to stabilize the structure of the hybrid scaffolds. Co-axial or co-electrospinning is a method where two or more solutions (polymer solution and biological molecule solution) are coaxially or simultaneously electrospun together, which have different fluid-based channels feeding them to the central feeder for electrospinning. These kinds of electrospun materials may have core-shell structures formed from two or more different components.^{[85, 86]} Covalent immobilization deals with biomolecules or drugs being chemically bonded to the electrospun fiber surface by covalent end group linkages.^{[87, 88]}

Figure 4.

Schematic illustrating therapeutics-loaded nanofibers for wound healing. (A) Different approaches used for loading therapeutic molecules to nanofibers. (B) Schematic representation of the incorporated of dimethyloxalylglycine-loaded mesoporous nanoparticles to electrospun nanofibers for wound healing. Adapted with permission from Ref. [93]. Copyright 2018 Elsevier.

5.1. Delivery of small-molecule drugs

Small-molecule drugs have been widely used for wound healing, and many are promising candidates for combinatorial use with wound dressing.^{[81, 82]} These drugs mainly include hormone, antimicrobial agents, anti-inflammatory drugs, analgesics, and their combinations. Mirmajidi et al. reported a CS-PCL/PVA-melatonin (MEL)/CS-PCL three-layer nanofiber wound dressing for the rapid wound healing.^[89] The in vivo results showed that 20% MEL composed nanofibers significantly reduced the wound healing time, which may have potential for treating different wound types like trauma, diabetic ulcer and burn.^[87] In a different study, aligned curcumin-loaded poly(lactide-co-glycolide) (PLGA) nanofiber membranes were prepared followed by high density surface grafting of heparin for wound healing.^[90] The sustained delivery of curcumin controlled the oxidative stress and inflammatory cascade during the wound healing. In addition to that, the heparin grafted nanofibers showed higher cell migration rate in vitro and accelerated reepithelization in vivo. Similarly, Agarwal et al. reported curcumin-loaded silk fibroin nanofibers blended with polymers like PCL and PVA for wound healing.^[91] The in vitro release profile showed a sustained and prolonged drug release from the nanofibers. The study revealed that the curcumin-loaded silk based nanofiber mats exhibited higher wound healing efficacy as compared to toxic/normal/placebo control groups on 14^th day of the treatment. In a separate work, Meng et al. reported the use of a non-steroidal, anti-inflammatory drug, Fenbufen (FBF), with PLGA/gelatin (9:1) for blend electrospinning.^[92] The release of FBF was significantly slow due to glutaraldehyde crosslinking when compared to non-crosslinked PLGA/gelatin fibers. The release profile showed a steady and gradual release of FBF over 25 h. However, this nanofiber dressings were not examined in in vitro and in vivo. In another study, Ren et al. reported an efficient strategy for wound healing which combined porous nanofiber membranes with drug-loaded mesoporous silica nanoparticles.^[93] Figure 4B represents the use of mesoporous silica nanoparticle-loaded aligned nanofibers for wound healing. The in vitro and in vivo results showed that the composite wound dressing with dimethyloxalylglycine could stimulate neo-vascularization, re-epithelialization, and collagen formation in diabetic wound beds, which eventually resulted in improved healing.^[93] In addition, Guo et al. prepared a core-shell nanofiber system composed of CS/PEO/lidocaine in the shell and PCL/curcumin in the core using coaxial electrospinning for sequential delivery system.^[94] Lidocaine chloride and embedded curcumin served as a pain reliever and an anti-inflammatory agent, respectively. By loading CS with sodium bicarbonate, the dressing gained pH-responsive functionality. Under acidic pHs, protonation of CS occurred and helped in the generation of carbon dioxide by sodium bicarbonate, which promoted the loosening of fibers for drug release. The burst release of lidocaine immediately alleviated pain, while curcumin’s gradual release modulated inflammation and also acted as an antibacterial agent. Kharaghani et al. also reported a core-shell nanofiber dressing for the sequential delivery of diclonfenac sodium salt and gentamicin sulfate in the wound healing application although limited biological characterizations were performed.^[95]

5.2. Delivery of growth factors

Growth factors play an important role in wound healing from the initial phase, like platelet aggregation to myofibroblast proliferation, re-epithelization, and extracellular matrix remodeling.^[1–3] For example, common growth factors like epidermal growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF) has been played a pivotal role in the wound healing process at different stages. Among them, EGF and FGF involved in the early stages of wound healing, whereas PDGF and VEGF get involved in the in later stages. ^[2] For the rapid wound healing, the controlled delivery of growth factors is introduced through various delivery systems such as biomaterial scaffolds, and nano/micro delivery carriers. To deliver the growth factors via scaffolds, the growth factors must be preserved during different stages in the application (e.g., from fabrication, storage, to degradation or, partial degradation). Growth factors usually have short half-lives, and the temporospatial growth factor concentrations must be maintained.^[96] Neovascularization or angiogenesis is one of the critical steps in wound healing, the VEGF or VEGF mimic peptides can enable the rapid vascularization during the wound repair. In addition to that, vascular engineering during the wound healing process often involves various cells, including epithelial cells, vascular endothelial cells, platelets, fibroblasts, vascular smooth muscle cells, and macrophages. ^[1–3]

EGF is an excellent wound healing agent but has a very short half-life. To facilitate that, Schneider et al. reported EGF-loaded electrospun silk fibroins (SF)/PEO nanofiber scaffolds for the rapid wound healing.^[84] EGF was added to the SF/PEO solution in methanol and was spun together to form EGF-loaded SF/PEO nanofiber mats. EGF released 25% from nanofiber mats over 170 h. EGF-loaded SF/PEO nanofiber membranes showed remarkable healing in an in vitro wound healing model by co-culturing human dermal fibroblasts (HDF) and normal human keratinocytes (NHK). In another study, to control the sustained delivery, Choi et al. introduced the concept of surface conjugation of EGF onto PCL-PEG block co-polymer electrospun fiber scaffolds for examining the effect of the scaffolds on human keratinocytes.^[97] It was observed that the expression of the keratinocyte-specific genes increased significantly in the case of EGF conjugated fibers. Similarly, Gumusderelioglu et al. also used elctrospun PCL nanofiber scaffolds containing collagen for the conjugation of EGF.^[98] The PCL/collagen scaffolds with conjugated EGF showed a massive increase in the differentiation of keratinocytes. This was confirmed through the changes in the genetic expressions, eventually resulting in an overall faster wound healing process.

FGF growth factor plays a key role towards activating vascular endothelial cells, keratinocytes, and fibroblasts which is essential during rapid wound closure in the proliferation and remodeling phases. Yang et al. loaded polyplexes of basic FGF and poly (ethylene imine) in electrospun poly(_D,L-lactide)-poly(ethylene glycol) (PELA) nanofibers and observed the transfection of mouse embryo fibroblasts (MEFs).^[99] The scaffolds showed rapid re-epithelization on diabetic rat skin wounds and the wounds healed within 4 weeks. In a different study, Mirdailami et al. reported the synergistic effect of FGF and EGF on the proliferation of human skin fibroblasts (HSF). PLGA microspheres containing FGF and EGF were introduced to PLGA/PEO nanofibrous mats.^[100] The release of the dual growth factors on seeded HSFs showed enhanced proliferation when compared to individual FGF in the scaffolds.

Generally, VEGF and VEGF mimicking peptides played a significant role in the neo-vascularization in the wound healing process. It is also known to promote epithelization and enhance collagen deposition. Guex et al. reported that surface-immobilized VEGF on electrospun PCL nanofibers enhanced structural stability and sustained delivery during the wound healing process.^[88] In this study, the electrospun PCL fibers were first treated by plasma to introduce carboxylic acid groups, which were converted to amine-reactive esters by NHS/EDC chemistry. Subsequently, VEGF was covalently bonded to the esters to form stable amide bonds with PCL fibers. These scaffolds enhanced the proliferation of endothelial cells compared to native PCL scaffolds. In a different study, Zhao et al. also showed the importance of a long and steady release profile of VEGF on the enhanced performance of the endothelial cells during wound healing.^[101] In this study, VEGF containing PLGA nanofiber scaffolds produced by negative-voltage emulsion electrospinning showed a more sustained release of VEGF up to 18 days, while more than 90% of VEGF were released from scaffolds fabricated by positive-voltage emulsion electrospinning in the first three days. In addition, scaffolds produced by negative-voltage emulsion electrospinning also demonstrated better efficacy in enhancing the functions of endothelial cells when compared with the ones generated by positive-voltage emulsion electrospinning.

PDGF is another class of growth factors, which controls the involvement of platelets during wound recovery and takes active participation in re-epithelization and angiogenesis. Interestingly, Li et al. demonstrated that vascular smooth muscle cells (VSMC) showed better adhesion to core-shell dextran-PLCL (DEX/PLCL) electrospun fibers loaded with PDGF-bb when compared to DEX/PLCL fibers without incorporation of PDGF-bb^[100] where the PDGF-bb-PLCL core-shell fibers were produced by coaxial electrospinning with a feed ratio of 3:1.^[86] This material was also tested to quantify the proliferation of NIH 3T3 cells, and the proliferation of NIH 3T3 cells increased by >40% in the presence of PGDF-bb-loaded fibers. In addition, Xie et al. achieved dual growth factor delivery from fiber meshes incorporated with VEGF and platelet-derived growth factors (PDGF-bb) fabricated by CS/PEO blend electrospinning for wound healing.^[102] Briefly, PLGA nanoparticles were loaded with VEGF and PDGF-bb in the ratio of 2:1, and were electrospun with CS/PEO (Figure 5A and B). The electrospun nanofiber scaffolds showed significant antimicrobial activities against S. aureus over 10 h and supported 156.8 ± 6.6% human dermal fibroblast (HDF) growth on day 7. Studies performed on a normal rat full-thickness skin wound model demonstrated that nanofiber scaffolds significantly accelerated the wound healing process by promoting angiogenesis, increasing re-epithelialization, and controlling granulation tissue formation (Figure 5C).

Figure 5.

Growth factors induced wound healing. (A) Schematic illustrating the fabrication and use of nanoparticle-embedded electrospun nanofibers loaded with two growth factors. (B) Characterization of nanoparticle-embedded electrospun nanofibers. (a) SEM images of nanofiber scaffolds: 2:1 CS/PEO-NPs, (b) 1:1 CS/PEO-NPs. (c) Fluorescent image merges monochrome image of ICG-loaded NPs in CS/PEO fibers, as indicated by arrows. (C) Histological evaluation of wounds treated by CS/PEO-NP meshes. Adapted with permission from Ref. [102]. Copyright 2013 Elsevier.

The scope of the involvement of multiple growth factors in a single scaffold system overall makes the system complex but this also enhances the possibility of better tissue generation in terms of both time and effectiveness of the overall procedure. Lai et al. used multiple growth factors like FGF, EGF, PDGF, and VEGF in the single nanofiber dressing.^[103] The FGF and VEGF-loaded gelatin nanoparticles were kept in HA solution whereas PDGF and EGF-loaded gelatin nanoparticles were kept in collagen solution, and both were electrospun separately but using a common collector. The scaffold possessed similar mechanical properties as human skin and showed rapid vascularization and deposition of collagen in a diabetic rat wound model.

5.3. Cell therapy

In the past few decades, stem cell therapy has served as a hallmark in tissue repair and regeneration, particularly in wound healing.^{[104, 105]} Stem cells produce pro-regenerative cytokines that contribute to rapid wound healing.^[105] Generally, various stem cells (e.g., mesenchymal stem cells, adipose stem cells, and hematopoietic stem cells) are used for the treatment of pressure ulcers, limb ischemia, chronic wounds, and burn wounds.^[106] Due to the biomimicry to skin ECM in both composition and morphology, electrospun nanofibers have served as scaffolds/carriers that can regulate cell behavior. Aligned nanofibers have been demonstrated to guide and promote cell migration. Figure 6A shows the influence of the different alignments of the nanofiber scaffolds on cell attachment and proliferation.^[107] The more elongated cells were observed on the aligned nanofiber mats rather than the random or crossed nanofiber mats (Figure 6B). But the crossed nanofiber dressings showed the best efficacy in the treatment of diabetic rat wounds (Figure 6C).^[107] In a different study, Chen et al. reported a novel 3D scaffold consisting of radially or vertically aligned nanofibers that, in combination with BMSCs, improved diabetic mouse wound healing (Figure 7).^[108] In addition, these scaffolds can provide a personalized treatment by tailoring the size, depth, and shape of diabetic wounds (Figure 7A, B). In vivo results showed that the BMSC-laden, 3D scaffolds significantly enhanced granulation tissue formation, angiogenesis, and ECM deposition and simultaneously elicited a pro-regenerative response to accelerate wound healing. Given the relatively simple mechanical features, the efficacy of such scaffolds could be further enhanced when combining with various biological therapies.^[108] In another study, Kanji et al. expanded human umbilical cord blood-derived CD34+ cells on aminated polyehersulfone nanofiber scaffold coated coverslips and injected the expanded cells for healing cutaneous wounds developed in streptozotocin-induced diabetic NOD/SCID mice.^[109] The local administration of CD34+ cells to the wound site significantly accelerated wound closure because of improved re-epithelialization, neovascularization, decreased sustained pro-inflammatory activity of NF-κB, and its downstream effector molecules TNF-α, IL-1β, and IL-6 at the wound bed.^[109]

Figure 6.

Orientation of nanofiber in wound healing. (A) (a-c) SEM images of the different orientations of nanofiber. (B) (a-f) Morphology of fibroblasts cultured for 24 h on nanofibrous scaffolds. Fluorescent staining of F-actin (green) with phalloidin-FITC. Cell nuclei are stained blue with DAPI. (C) H & E staining of wound sections at various time points. Wound areas are traced with a dashed white line. Adapted with permission from Ref. [106]. Copyright 2018 Royal Society of Chemistry.

Figure 7.

3D nanofibrous scaffolds for wound healing. A (a-d) Top and side view of 1-mm thick radially aligned scaffold and (e-h) Top and side view of 1-mm thick vertically aligned scaffold. Double-headed arrows indicate the alignment of nanofibers. B (a) Schematic illustrating the application of 3D scaffolds consisting of radially aligned nanofibers in stages 1 & 2 DFU healing, which aim to accelerate the re-epithelialization of superficial wounds, (b) Schematic illustrating the application of 3D scaffolds consisting of vertically aligned nanofibers in stages 3 & 4 DFU healing, which aim to promote the formation of granulation tissues of deep wounds, (c) The potential mechanism of 3D scaffolds consisting of radially aligned nanofibers for diabetic wound healing, including enhancing angiogenesis, granulation tissue formation, ECM deposition, and re-epithelialization, and (d) The potential mechanism of 3D scaffolds consisting of vertically aligned nanofibers for diabetic wound healing, including enhancing angiogenesis, granulation tissue formation, and ECM deposition. Adapted with permission from Ref. [108]. Copyright 2020 Elsevier.

5.4. Skin grafting

Skin grafting is a class of surgical procedures that involve transplanting healthy skin onto an injury site. ^[110,111] Skin grafting (e.g., autologous split thickness skin grafts (STSG) (mesh skin grafts and MEEK skin grafts) and minced skin grafts) is often employed to treat burns and chronic wounds.^[112–114] Unfortunately, these micrografts require a significant workload from harvest to implantation. Moreover, for larger defects, labor and tissue harvesting may not be feasible due to the limited expansion ratio.^[115] Sharma et al. simply placed minced STSG between the two sheets of PLA nanofiber membranes as a dermal substitute.^[116] An outgrowth of skin cells from minced pieces of split thickness skin seeded on the nanofiber membrane and collagen deposition was observed. Inspired by the Meek skin graft and nanofiber scaffolds, Ma et al. developed a unique class of nanofiber skin grafts in a ‘sandwich’ form: radially-aligned nanofiber membranes at the bottom, nanofiber membranes with square-arrayed microwells and aligned topographical cues at the top, and micro skin tissues seeded to microwells in between, for applications in skin injury repair (Figure 8).^{[111, 117]} It was found that the proliferation and migration of fibroblasts seeded to each microwell can cover the entire surface of square-arrayed microwell membranes within 14 days in vitro, when the distance between two adjacent microwells was 3 mm. In contrast, it took more than 21 days for cells to cover the whole surface of random or aligned nanofiber membranes. The in vivo study showed that sandwich-type nanofiber skin grafts presented a uniform distribution of micro skin tissues, enhanced the ‘take’ rate of micro skin tissues, and accelerated the re-epithelialization of rat excisional wounds (Figure 9). These results indicated sandwich-type nanofiber skin grafts may be promising in healing large burns and chronic wounds. Later on, Fu et al. attempted to form tissue constructs by seeding cell spheroids to the arrayed holes created on expanded nanofiber scaffolds.^[118] Similarly, minced skin tissues could be seeded to the arrayed holes to form 3D nanofiber skin grafts for repair of burn or chronic wounds.

Figure 8.

Fibroblast culture on nanofiber membranes with different organizations. NIH 3T3 fibroblasts were seeded on aligned (A), random (B), microwell (C), and flat well (D) nanofiber membranes and incubated for 3, 7, 10, 14, and 21 days. Insets illustrated cell suspension droplets on the surface of nanofiber membranes. The distance between the two adjacent microwells was 3 mm. Fluorescence microscopy images showed living cells cultured on nanofiber membranes which were stained with fluorescein diacetate in green. All scale bars are 1 mm. Adapted with permission from Ref. [117]. Copyright 2014 Elsevier.

Figure 9.

Nanofiber skin grafts for wound healing. (A) Transplanted microskins indicated by small black arrows in sandwich-type nanofiber scaffolds were transplanted satisfactorily on wounds with a uniform distribution at day seven post-surgery. (B) Re-epithelialization derived from microskins occurred along the wound bed on day 14 after surgery. (C) The wound was completely closed by re-epithelialization derived from microskins indicated by black arrows on day 21 after surgery. (D) Magnified view of the region d in (A), transplanted microskins contained both epidermal and dermal layers indicated by white dashed lines and white arrowheads, respectively, confined by the nanofiber microwell indicated by black dashed lines. (E) Magnified view of the region e in (D), showing small blood vessels indicated by white arrowheads, large collagen bundles, and a few fibroblasts in the dermal layer of the microskin. (F) Magnified view of the region f in (B), showing stratified epithelial cells derived from microskins crept along the surface of wound bed toward the adjacent microskin indicated by white dash lines. Simultaneously, the dermal layer of microskins began integrating with the wound bed indicated by white arrowheads. (G) Magnified view of the region g in (C), showing epidermal cells migrated from the two adjacent micro skin resurfaced the wound indicated by white dash lines Adapted with permission from Ref. [117]. Copyright 2014 Elsevier.

6. Conclusion and Future Perspectives

This mini review highlights the use of electrospun nanofiber-based materials for wound management in terms of hemorrhage control, prevention and treatment of infection, pain relief, and promotion of healing. Due to the ultra-absorption property, 3D expanded nanofiber scaffolds and nanofiber sponges exhibit excellent hemostatic efficacy. Electrospun nanofibers functionalized with immunomodulating compounds and antimicrobial agents are effective in management of wound infection. Nanofibers can release analgesics to relieve pain. In addition, electrospun nanofibers can serve as scaffolds/carriers for effective delivery of therapeutics, cells, and skin tissues for promotion of wound healing.

In recent years, dressings based on electrospun nanofiber mats have been translated into FDA-approved devices for wound management. Looking ahead, direct in situ application of short nanofibers via injection and in situ crosslinking may offer an advantage over nanofiber mats in that they can fill the irregularly shaped wounds and thus alleviate the need for wound packing.^[119] Similarly, porous nanofiber microspheres could be used as a filler for wounds.^[120] Such microspheres could also be applied using injectable shear-thinning media or as cell carriers and sprinkled onto wound surfaces prior to dressing applications.

Combinatorial therapies utilizing or repurposing nanofibers may offer a variety of increased functionality for wound healing. For example, it is possible to create nanofiber objects with functional drug gradients, allowing regional drug delivery.^[121] Further, repurposing of nanofibers into solid and mechanically robust microneedles may introduce a new class of hybrid nanofiber microneedles capable of burst and sustained drug release.^[61] Such a device could allow for pain relief, hemostasis, and antimicrobial activity simultaneously and within designated anatomical regions. Combinatorial use of 3D bioprinting and nanofiber materials may allow for preparation of an all-in-one wound dressing in a patient-specific manner for repair of different kinds of wounds.

Biographies

Johnson V. John was born in Kerala state in India. He received his B.Sc. degree in Chemistry from Kannur University, and M. Sc. in Biochemistry from Bharathidasan University, India. In 2016, he completed Ph.D. degree under the supervision of Prof. Il Kim in the Department of Polymer Science and Engineering, Pusan National University, Republic of Korea. Then, he joined Prof. Carlo. D. Montemagno’s Lab as a postdoctoral Research Associate, at the University of Alberta, Canada (2016–2018). Then, he joined Xie’s lab in February 2018 as a postdoctoral research fellow. His research interests include the fabrication of different biomaterials for nanomedicine, tissue engineering, therapeutic delivery and 3D cell culture.

Alec McCarthy received his B.S. in Biological Systems and Biomedical Engineering from the University of Nebraska-Lincoln in 2018. During his undergraduate, he was an NIH INBRE Fellow and conducted research relating to small molecule synthesis, non-viral gene delivery, and engineering biomedical devices. He joined the Xie Lab in 2019 as the first Ph.D. student in the Regenerative Medicine and Biomaterial Design Program at the University of Nebraska Medical Center. His research interests include biomedical device design, tissue engineering, biomaterials, and process engineering.

Anik Karan completed his B.E. from West Bengal University of Technology in Kolkata, West Bengal, India with a major in electronics and instrumentation engineering. He completed M.S. and Ph.D. in biomedical engineering from Cellular Neuroscience Laboratory, Louisiana Tech University under the supervision of Dr. Mark DeCoster. He joined Nano-Assembly Laboratory in Louisiana Tech University as a research associate working for L’Oreal under Dr. Yuri Lvov. He currently works as a postdoctoral research associate in Xie Lab in the Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program at UNMC. His research interests are nano/micromaterials fabrication and characterization, biomaterials, drug delivery, and nanotechnology.

Jingwei Xie received his B.S. and M.S. from Nanjing University of Technology, China, and his Ph.D. from the National University of Singapore (2007). He worked as a postdoctoral fellow in the Xia group at Washington University in St. Louis. He is currently a professor in the Department of Surgery-Transplant and Holland Regenerative Medicine Program at UNMC. He is also an adjunct faculty in the Department of Mechanical & Materials Engineering at the University of Nebraska-Lincoln. His research interests include biomaterials, drug delivery, nanomedicine, tissue engineering, regenerative medicine, wound infection and healing, and hemostasis.