Nanomaterial strategies in wound healing: A comprehensive review of nanoparticles, nanofibres and nanosheets

Abstract

Wound healing is a complex process that orchestrates the coordinated action of various cells, cytokines and growth factors. Nanotechnology offers exciting new possibilities for enhancing the healing process by providing novel materials and approaches to deliver bioactive molecules to the wound site. This article elucidates recent advancements in utilizing nanoparticles, nanofibres and nanosheets for wound healing. It comprehensively discusses the advantages and limitations of each of these materials, as well as their potential applications in various types of wounds. Each of these materials, despite sharing common properties, can exhibit distinct practical characteristics that render them particularly valuable for healing various types of wounds. In this review, our primary focus is to provide a comprehensive overview of the current state‐of‐the‐art in applying nanoparticles, nanofibres, nanosheets and their combinations to wound healing, serving as a valuable resource to guide researchers in their appropriate utilization of these nanomaterials in wound‐healing research. Further studies are necessary to gain insight into the application of this type of nanomaterials in clinical settings.

1. INTRODUCTION

Wound healing involves a complex series of biological and molecular processes encompassing cell proliferation, cell migration and extracellular matrix (ECM) deposition. Furthermore, wound healing is a physiological procedure that repairs damaged tissues and restores skin integrity. The process of skin wound healing typically includes haemostasis, inflammation, proliferation and remodelling. ¹ The current wound treatment methods include debridement and dressings like hydrocolloids, foams, hydrogels and negative pressure wound treatment. However, these methods are limited due to issues like poor mechanical properties, pain and infection susceptibility. Nanomedicine, which can reduce inflammation, monitor infections and expedite wound healing, has the potential to replace traditional methods. ²

Nanomaterials can interact with the wound‐healing process through their inherent nanoscale properties, such as the release of ions or the production of reactive oxygen species (ROS). These properties can impact various molecular and cellular pathways, thereby facilitating the transition of chronically inflammatory stalled wounds towards the healing phase’. ³ Nanomaterials are currently employed both as direct antimicrobial agents, harnessing their inherent antimicrobial activity, and as carriers for antibiotics and other antimicrobial agents. ⁴ Nanomaterials are routinely classified into three principal groupings dependent on their morphological and structural features: nanoparticles (NPs), nanofibres and nanosheets. These nanomaterials represent novel classes of materials that exhibit a number of unique characteristics, making them highly promising in many biomedical applications, including wound healing. ⁵

NPs can improve wound healing by delivering medicinal substances like antibiotics, growth factors and anti‐inflammatory agents. ³ Demand for dressing materials with wet adhesive and antibacterial properties is high, especially for infected wounds. ⁶ NPs can be engineered to bind with immune cells or fibroblasts, delivering therapeutic payloads to specific targets. ⁷ Nanofibres for wound dressing offer high surface area to volume ratio, mechanical strength and adjustable porosity, creating an optimal environment for healing and mimicking the ECM, ⁸ providing a scaffold for cell attachment and growth. ⁹ Polymer nanosheets are used as dressing materials due to their thin thickness, large surface area, tunable flexibility, and adhesion, making them ideal for wound healing ¹⁰ and providing mechanical support and protective barrier protection. ¹¹

This article provides an overview of the wound‐healing process, encompassing its distinct phases and the influential factors contributing to it. Additionally, the role of NPs, nanofibres, nanosheets and NP‐embedded polymeric wound dressings in augmenting the wound‐healing procedure is elucidated.

2. WOUND HEALING

A wound is a serious injury resulting from damage or disruption to the skin's normal structure and function. This can impact the epithelium layer of the skin or subcutaneous tissue, which can affect blood vessels, nerves, muscles, tendons and bone. ¹² Wounds are classified into acute and chronic types, with acute wounds healing within 4–12 weeks, restoring functional and anatomical skin integrity. ¹³ Chronic wounds are difficult to heal due to underlying conditions like diabetes, autoimmune diseases and venous stasis and can be worsened by prior infections, inflammation, tumours or exposure to physical agents. The delayed healing process, lasting over 12 weeks, can increase the risk of infections. ¹⁴ Wound healing is a complex process involving four stages: haemostasis, inflammation, proliferation and remodelling, regulated by growth factors, cytokines and ECM proteins. Disruptions in this process can lead to delayed or impaired healing. ¹⁵ , ¹⁶ In the following section, each stage will be explained in detail.

2.1. Haemostasis phase

Haemostasis is the initial stage of wound healing that halts bleeding caused by vascular damage. It encompasses three pivotal stages: vasoconstriction, primary haemostasis and secondary haemostasis. Platelets and fibrinogen are key cells and components, respectively, involved in this process. ¹⁷

2.1.1. Vasoconstriction

After an injury, blood vessels constrict rapidly to reduce bleeding, triggered by vasoconstrictors like endothelin released from the damaged endothelium. Circulating catecholamines and prostaglandins also regulate this constriction in response to injury. ¹⁸ Platelets produce platelet‐derived growth factor (PDGF), which temporarily reduces bleeding in vessel walls. However, hypoxia and acidosis can recur, so coagulation cascade is needed to prevent long‐term bleeding. ¹⁹

2.1.2. Primary haemostasis (platelet plug formation)

During haemostasis, platelets circulate near endothelial cells, which prevent platelet activation and attachment. After injury, the thrombogenic subendothelial matrix is exposed, triggering platelet binding and a signalling pathway that enhances attachment to platelets and the ECM. Integrins play a crucial role, and active platelets release thromboxane A2, forming the platelet plug. ²⁰ Additionally, platelets release growth factors and cytokines such as PDGF, transforming growth factor (TGF), epidermal growth factor (EGF) and insulin‐like growth factor (IGF). These factors are released within the first hour and continue for up to 7 days, affecting other cell types. Platelet‐rich plasma (PRP) is tested for injury treatment in animals. ²¹

2.1.3. Secondary haemostasis (coagulation)

Platelets play a crucial role in coagulation by activating factor X, which converts prothrombin into thrombin and fibrinogen. Factor XIII then crosslinks fibrin, binding with the platelet plug to create a definitive thrombus ²² Alpha granules from platelets release TGF‐β1, a chemoattractant for recruiting phagocytes. Platelet receptors facilitate cell–cell and microbial interactions and release growth factors like PDGF, TGF‐β1, fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). These factors engage various cells, activating neutrophils, detecting pathogens, trapping microbes and modifying immune responses. In summary, platelets facilitate the transition to the next stage by secreting substances that mobilize inflammatory cells. ¹³ , ¹⁷

2.2. Inflammation phase

After haemostasis, the inflammation phase begins with oedema and cellular cytolysis. Damaged cells activate the inflammasome, converting pro‐interleukin (IL) to IL. Keratinocytes release IL‐1a, IL‐33 and high‐mobility group box 1 (HMGB1), affecting inflammation. ²³ During the inflammation phase, phagocytes and immune cells migrate to the wound site to prevent infection. ¹³ , ²⁴

Neutrophils, primary responders to wound healing, utilize increased capillary permeability to migrate as inflammatory cells. They play a crucial antimicrobial role and persist within the wound for up to 24 h. Neutrophils release factors that enhance their infiltration, including toxic granules, oxidative bursts and phagocytosis. ²³ They possess three distinct granules: azurophilic, specific and gelatinase, each with significant roles. ²² Neutrophil activity changes within a few days after wound healing, subsequent to the complete removal of contaminating bacteria, with concurrent neutrophil apoptosis. Macrophages, 48–72 h after injury, form the second wave of cell migration, drawn to the wound site through chemoattractive agents. They engage in phagocytosis (type M1/pro‐inflammatory), targeting both neutrophils and cell remnants. Macrophages have an extended lifespan and maintain functionality under lower pH conditions. Macrophages transition from a pro‐inflammatory M1 state to an anti‐inflammatory M2 state, playing a crucial role in the inflammatory response. They provide potent tissue growth factors, such as TGF‐β, along with other mediators such as TGF‐α and FGF, which activate various cell types, facilitating tissue repair and regeneration. ²⁵ , ²⁶ T lymphocytes appear in the late inflammatory phase of wound repair, influencing wound resolution and remodelling. The inflammation phase lasts 1–4 days and prepares for regeneration. Immune cells produce growth factors and cytokines, recruiting cells for the proliferation phase. ¹³

2.3. Proliferative phase

The proliferative phase begins between days 4 and 7 and continues for up to 21 days after an injury. The wound fulfils with new granulation tissue, which is characterized by the presence of numerous fibroblast cells, high levels of glycosaminoglycans and proteoglycans, immature collagen type III and new blood. ²⁷ This phase replaces the provisional network of fibrin and fibronectin and involves epithelial proliferation and migration of keratinocytes. The various processes that occur during the proliferative phase are briefly discussed below.

3. FIBROBLAST MIGRATION AND COLLAGEN SYNTHESIS

After an injury, fibroblasts proliferate in the first 3 days and migrate to the wound, attracted by factors like TGF‐β, PDGF and FGF‐2. They produce collagen, crucial for skin regeneration. By the first week, an abundant ECM accumulates, supporting cell migration and repair. Collagen type 3, a key component in wound healing, is highly expressed in granulation tissue. Myofibroblasts, a subtype of fibroblasts, play a pivotal role in wound contraction and collagen synthesis. They express smooth muscle actin (SMA), which generates contractile forces. They also contribute to tissue remodelling through the secretion of matrix metalloproteinases (MMPs). ²⁸

4. ANGIOGENSIS AND GRANULATION TISSUE FORMATION

The diminished blood supply and heightened cellular metabolism involved in the process of repairing an injury result in the development of hypoxia within the wound tissues, serving as a pivotal stimulus for angiogenesis. The wound‐healing process relies on the establishment of new blood vessels, which are facilitated by various angiogenic factors, such as FGF, VEGF, PDGF, angiogenin, TGF‐α and TGF‐β. Resident endothelial cells respond to these factors, resulting in the development of small ‘buds’ or ‘sprouts’ that merge with other buds, forming a functional capillary loop. ²⁹ Granulation tissue, composed of type III collagen, fibroblasts and blood vessels, forms during wound healing. It has a pink or red colour and uneven texture, showing resilience to easy bleeding. ²² Darkly pigmented tissue can indicate underlying issues like infection, ischemia or poor tissue perfusion, which is crucial in wound care and management.

5. EPITHELIALIZATION

In the final stages of the proliferation phase, epidermal cells migrate across the wound surface, originating from wound margins or remnants of hair follicles, sebaceous glands and sweat glands. These translucent, whitish‐pink cells spread across the granulation tissue, forming a continuous epithelial layer. ³⁰ TNF‐α promotes keratinocyte proliferation and intracellular adhesion molecule‐1 expression during this phase. ³¹

5.1. Remodelling phase

Wound‐healing transitions into the final remodelling stage, lasting 14 days to 2 years. During this stage, various proteinases play a crucial role in wound healing, regulated by time‐dependent and spatial changes in expression patterns. Most proteinases undergo alterations in activity and conformation in response to the wound environment. Type III collagen bridges wounds and facilitates tissue reformation during wound healing. ³² Myofibroblasts coordinate the breakdown of granulation tissue and replacement with long‐lasting type I collagen. Successful wound healing requires careful coordination of degradation and synthesis. ¹³ Over‐degradation can lead to chronic non‐healing wounds, while over‐synthesis can cause excessive scar tissue. Variables like treatment strategy, burn depth, skin type, patient age and healing speed contribute to scar formation. ³³ Cytokines, ³⁴ including TGF‐β isoforms, play crucial roles in wound healing and scarring. ³⁵ Scar tissue formation is common in adults, while embryonic wound healing occurs without scarring. Embryonic wounds have lower levels of TGF‐β1 and β2 isoforms, while TGF‐β3 isoforms are higher. Adult wounds increase TGF‐β1 and β2 expression due to platelet degranulation, while TGF‐β3 is insignificant. ³⁶ , ³⁷ Understanding the different healing stages and effective factors can aid in wound‐healing management.

6. NANOMATERIALS AND WOUND HEALING

Nanomaterials are often categorized into three main groups based on their dimensional characteristics: NPs, nanofibres and nanosheets. These categorizations are primarily defined by the primary morphology and structure of the materials. Despite the fact that each of these nanomaterials shares common features in the wound‐healing process, they also possess certain exclusive capabilities due to their specific structures. To determine the most suitable wound treatment, it is important to have a good understanding of these unique properties. Here's a breakdown of these groups.

6.1. NPs in wound healing

NPs, ranging from 1 to 100 nanometres in size, play a crucial role in wound healing, controlling drug release, targeting delivery, infection control and bioactivity, with various shapes and forms.

6.1.1. Controlled drug release

Researchers can control the size, composition and surface properties of NPs to release therapeutic agents like growth factors or antimicrobial agents at the wound site.

NPs, as carrier materials, can increase the bioavailability of wound‐healing pharmaceuticals such as antibiotics, growth factors or anti‐inflammatory agents by enhancing their half‐life, improving their stability and solubility, inhibiting their degradation and minimizing their potential toxicity. ³

6.1.2. Targeted drug delivery

Functionalized NPs can be designed to specifically target certain cell types or tissues involved in wound healing. This targeted approach increases the efficiency of treatment and reduces potential side effects. Angiogenesis requires a dynamic and spatiotemporally controlled interaction between endothelial cells, the surrounding ECM microenvironment and angiogenic factors. Several nanomaterials have been described to promote angiogenesis in tissue regeneration scenarios. For example, gold NPs exert angiogenic value in wound repair by increasing the expression of angiogenic factors such as VEGF, angiopoietin 1 and angiopoietin 2. Silicate ions are an important group of inorganic biomaterials used for tissue engineering. They increase the expression of proangiogenic factors, including VEGF and FGF, and stimulate the nitric oxide (NO) production by endothelial cells. ³⁸ Several studies have shown that the size of NPs plays an important role in their antiangiogenic activities. For example, the core size of gold NPs with 20 nm plays an important role in VEGF binding in biological media and inhibited angiogenesis when compared to that of size 100 nm. ³⁹ It also reported that SiO₂NPs in size 25 nm had no outcome on the angiogenic reply of endothelial cells even at 2.5 nM but larger silicate nanoparticles (SiNPs) of size 57 nm successfully reserved VEGF‐induced retinal neovascularization and inhibited ERK 1/2 activation. Interestingly, NPs with antiangiogenic activities enhance collagen deposition and epidermal regeneration in the wound beds and treat hypertrophic scar building that is linked to pathological angiogenesis and increased microvascular content.

6.1.3. Antimicrobial properties

Nanomaterials, due to their antimicrobial properties and potential as carriers of antibiotics, are being used as direct antimicrobial agents. These NPs interact with bacterial cell walls, release toxic ions and induce oxidative/nitrosative stress, leading to bacterial growth inhibition or death through gene expression and protein synthesis regulation. ⁴

NPs release ions with varying antibacterial effects, such as iron nutrient for bacterial growth and survival, and copper and silver hydroxyl radicals damaging proteins, cell membrane integrity and DNA. ⁴⁰

NPs like silver, Au, CuO, TiO₂, ZnO, graphene and graphene oxide have antimicrobial properties. ⁴¹ , ⁴² The combination of NPs with polymer networks can enhance antibacterial performance. ⁴³ Nanocrystal silver is the most commonly used nanomaterial in wound dressing due to its low toxicity compared to silver sulphadiazine or silver nitrate.

6.1.4. Bioactivity

NPs can be coated with bioactive molecules, such as growth factors or peptides, which interact with cellular receptors, triggering specific cellular responses. This mimics the wound microenvironment, accelerating healing and managing inflammation in chronic wounds.

Wound healing requires a balance between oxidative stress and antioxidants. ⁴⁴ Nanomaterials like zinc oxide NPs and CeO₂ can reduce inflammation and oxidative stress, ⁴⁵ while chitosan promotes re‐epithelialization and granulation. Chitosan‐coated CeO₂ nanocubes are a promising nanocomposite for wound healing due to their anti‐inflammatory, antioxidative/nitrosative stress and wound‐regeneration capabilities. ⁴⁶

6.2. Nanofibres in wound healing

The thin nanofibres are made from materials like polymers, carbon nanotubes, metals and ceramics. They can be produced using techniques like electrospinning, template synthesis, self‐assembly and phase separation. ⁴⁷ Nanofibres dressings are used for wound management due to their high surface area to volume ratio, superior mechanical strength and adjustable porosity. They absorb fluids, act as a barrier against bacteria and are lightweight, comfortable and breathable, promoting faster healing. Extensive research has focused on optimizing electrospun fibres for effective wound dressings. ⁸ , ⁴⁸ Here are some key reasons why nanofibres are important in tissue engineering.

7. CELL ATTACHMENT AND MIGRATION

These ultra‐thin fibres provide a three‐dimensional scaffold that not only supports cell attachment but also facilitates cell migration and proliferation, crucial processes for tissue regeneration and wound closure. ⁴⁹

Nanofibres have a high surface area‐to‐volume ratio, resulting in a larger surface area than conventional materials. This increased surface area provides numerous cell attachment sites, promoting strong cell‐substrate interactions and facilitating cell migration and tissue formation, making them a valuable alternative. ⁵⁰

Nanofibres' porous structure enhances cell migration and proliferation. The interconnected pores within the nanofibre scaffold allow for efficient nutrient and oxygen exchange, facilitating cell viability and metabolism. This improves the infiltration of new blood vessels, promoting angiogenesis and tissue integration. ⁵¹ The surface chemistry of nanofibres can be modified to enhance cell attachment, migration and proliferation by functionalizing the surface with bioactive molecules like growth factors or cell adhesion peptides. These surface modifications can guide cell migration, stimulate proliferation and direct differentiation, enabling tissue regeneration. ⁵² , ⁵³

8. MIMICKING ECM

Nanofibres' fibrous arrangement resembles the natural ECM in tissues, creating a biomimetic environment that encourages cells to interact with nanofibres. When cells come into contact with nanofibre scaffolds, they recognize the familiar fibrous environment and respond with enhanced cellular activities, ⁵⁴ triggering essential responses for tissue remodelling and regeneration. These include reorganizing the cell's internal structure, spreading cells and forming focal adhesions. ⁵⁵ Nanofibres, with their nanoscale diameter, resemble natural ECM fibres like collagen or elastin, allowing cells to interact with them like native tissues. This aligns and migrates cells, crucial for tissue regeneration. Nanofibres can be modified with bioactive molecules like growth factors or peptides to mimic ECM biochemical cues. These molecules can be integrated into the nanofibre structure or immobilized on their surface. When cells interact with functionalized nanofibres, they receive specific signals regulating proliferation, differentiation and migration, promoting tissue regeneration. ⁵⁴ , ⁵⁶ , ⁵⁷

8.1. Moisture management and mechanical strength

Nanofibre‐based wound dressings regulate moisture levels at the wound site, promoting faster healing. These dressings absorb excess exudate while maintaining moisture balance, preventing a wet and macerated environment. Their high surface area‐to‐volume ratio allows them to efficiently absorb and retain exudate, preventing excess fluid accumulation, reducing bacterial growth risk and minimizing infection potential. ⁵⁸ Moisture is crucial for wound healing, promoting cell migration, proliferation and tissue synthesis. Nanofibre dressings maintain proper moisture levels, supporting tissue repair cells like fibroblasts and keratinocytes. Moisture also facilitates nutrient and oxygen transportation, cellular metabolism and granulation tissue formation. ⁵⁹ , ⁶⁰ Nanofibre dressings offer moisture‐regulating properties and mechanical strength to protect wounds and prevent physical disruptions. The nanofibres can be engineered to have appropriate tensile strength and flexibility and they form a protective barrier over the wound. This barrier shields the wound from external forces that can delay healing or cause further damage. ⁶¹ Nanofibre dressings are beneficial for wounds prone to movement or external forces, such as pressure ulcers or surgical incisions, due to their inherent strength and flexibility, minimizing the risk of dressing displacement or damage (Figure 1). This stability allows the wound to remain protected and undisturbed, facilitating the healing process. ⁶¹ , ⁶² , ⁶³

FIGURE 1.

Nanofibre dressings effect on wound healing.

8.2. Polymeric nanosheets in wound healing

Polymeric ultrathin films, also known as nanosheets, nanofilms or nanomembranes, are a new class of nanomaterials with a thin thickness and large surface area. They are free‐standing, allowing dynamic polymer properties to be expressed. Their high aspect ratio leads to unique interfacial and mechanical properties, including noncovalent adhesiveness, tunable flexibility and molecular permeability. ⁶⁴ , ⁶⁵

Polymeric nanosheets have shown promise in the field of wound healing. These nanosheets, often referred to as wound dressings or scaffolds, are designed to promote the healing process. Here are some key reasons why nanosheets in wound healing are important:

8.2.1. Conformability

Conformability is a crucial characteristic of polymeric nanosheets as it refers to their ability to adapt and conform to the shape and contours of the surface they come into contact with. Due to their thin and flexible nature, polymeric nanosheets have the remarkable ability to closely conform and adhere to various surfaces, including those that are irregular or curved. This conformability allows for intimate contact between the nanosheet and the substrate, facilitating efficient transfer of functional properties. ¹⁰ , ⁶⁶

Polymeric nanosheets' conformability is crucial in biological and biomedical applications, such as tissue engineering and wound healing. They can adhere to tissue surface irregularities, promoting cellular processes like attachment, migration and proliferation, essential for tissue regeneration. ⁶⁷ , ⁶⁸

8.2.2. Mechanical support

Polymeric nanosheets, despite their thinness, have the ability to provide mechanical support to wounds by forming a protective barrier. This barrier helps prevent physical disruptions and safeguards the wound during the healing process. The high flexibility and adhesiveness of nanosheets make them a suitable choice for biomedical applications, as highlighted in a study done by Takeoka et al. ⁶⁹ In another study conducted by Aoki, ⁷⁰ the efficacy of an ultrathin nanosheet containing poly‐L‐lactic acid with a thickness of 75 nm was assessed as a wound dressing material. The results indicated that wound healing was significantly improved during the early healing period of 4–6 days. By overlapping the poly‐L‐lactic acid nanosheet, a clear layer was formed just above the granulation tissue, which accelerated the wound‐healing process. Another study focused on the development of a collagen nanosheet modified with an antibacterial peptide (KRWWKWWRRC)‐modified collagen nanosheet known as KCN. This nanosheet exhibited mechanical strength and thickness comparable to human skin.

This study highlight the potential of nanosheets in wound management and their ability to enhance the wound‐healing process. The mechanical support, flexibility and adhesive properties of nanosheets make them promising candidates for biomedical applications, particularly as wound dressings.

8.2.3. Barrier function and wet adhesiveness

Nanosheets act as a barrier to protect wounds from contaminants and microorganisms, creating a clean environment conducive to healing. With the growing demand for dressing materials with antibacterial properties and wet adhesive features, nanosheets have emerged as promising to meet these demands, as highlighted in a study by Wu et al. ⁶ These polymer‐based nanosheets can effectively serve as dressing materials, providing a protective barrier and strong adhesion to the wound site. Additionally, nanosheets composed of biomaterials have shown potential in surgical sealing procedures. A study conducted by Zhang et al. ⁷¹ explored the application of such nanosheets in surgical sealing procedures. These biomaterial‐based nanosheets can offer sealing properties and assist in creating a secure closure during surgical interventions.

8.2.4. Bioactive loading platform

Nanosheets with bioactive loading platforms have been explored for wound‐healing applications. These platforms can incorporate growth factors, cytokines and antimicrobial agents, promoting inflammation modulation, angiogenesis and antimicrobial activity. They can also serve as scaffolds for tissue regeneration and functional tissue formation. ¹⁰ , ⁷¹ , ⁷²

Studies have shown the effectiveness of nanosheets loaded with antibacterial drugs, repairing materials and angiogenic hormones in enhancing wound healing. For instance, Saito et al. ⁶⁸ found nanosheets loaded with tetracycline effective in treating gastrointestinal tissue defects. Another study by Askari et al. ¹¹ found that combining honey and chitosan polymer nanosheets (CNSs) improved wound‐healing activities, including increased granulation area, collagen fibre density, new epithelium thickness, fibroblastosis and reduced inflammatory cell infiltration. Additionally, nanosheets have been combined with vasoactive intestinal peptide (VIP) and human recombinant basic fibroblast growth factor (bFGF) for angiogenic effects, promoting angiogenesis for effective wound healing. ⁷³ , ⁷⁴

8.3. NP‐embedded polymeric wound dressing

The ideal wound dressing should provide a moist, oxygen‐permeable environment, protect against infections, facilitate epidermal migration and angiogenesis and prevent traumatic removal post‐healing. ⁷⁵ , ⁷⁶ , ⁷⁷

Inefficient wound dressings can slow healing. Researchers are exploring nanoscale scaffolds due to their properties like bioactive compound distribution, high porosity, mechanical strength and ECM mimicry. NP dressings combine NPs into scaffolds to improve their characteristics such as adding silver nanoparticles to increase antibacterial properties. ⁷⁸ , ⁷⁹ , ⁸⁰ Furthermore, the outstanding characteristics of NPs, including their large surface area, ultrafine sizes, biocompatibility and low cytotoxicity, have provided wide applications for them. ⁸¹ , ⁸² NPs, due to their smaller size and ability to diffuse into bacterial cell walls, ⁸³ , ⁸⁴ , ⁸⁵ can be used as an alternative to antibiotics in wound dressings due to fewer side effects and fewer microbial resistance. ⁸⁶ The design should have essential properties like nontoxicity, biocompatibility, porosity and vapour and air permeability, mimicking the ECM structure. ⁸⁷ Combining antibacterial NPs with polymeric‐based nanofibres can achieve these properties. ⁸⁸ This can be achieved through different methods, including the direct blending method, UV‐irradiation method, silver mirror reaction method and thermal treatment method, as shown in Figure 2. Inorganic NPs can be embedded in polymeric wound dressings for wound healing, ⁸⁹ , ⁹⁰ , ⁹¹ offering superior antibacterial effects. Their activity and toxicity are influenced by factors such as size, surface chemistry, zeta potential, polydispersity index and chemical composition. ⁹²

FIGURE 2.

Schematic illustration of different methods to synthesize AgNPs‐loaded nanofibres. (A) Direct blending method; (B) UV‐irradiation method; (C) silver mirror reaction method and (D) thermal treatment method.

Various types of metallic NPs, including iron NPs, copper NPs, zinc NPs, silver NPs, cerium oxide NPs, and so forth, have been studied. ⁹⁰ , ⁹³ , ⁹⁴ , ⁹⁵ AgNPs have the potential to enhance wound healing due to their anti‐inflammatory and antibacterial properties, which accelerate healing and can be easily modified for drug delivery. ⁹⁶ , ⁹⁷ , ⁹⁸ AgNPs are used in bioactive wound dressings due to their low systemic toxicity and strong antimicrobial effects against various bacteria. ⁷⁸ , ⁹⁹ , ¹⁰⁰ , ¹⁰¹ They disrupt proteins in bacterial cell membranes and interact with DNA molecules to induce cell death. ⁹⁹ However, they can cause significant damage due to their spread throughout the body. To minimize side effects, disposal options are recommended, and AgNP‐loaded nanofibres have shown advantages like high loading capacity and controllable release mechanisms, by which local antibacterial effectiveness can be improved, and the systemic toxicity of Ag ions will be decreased. ⁹⁸ There are some publications reporting the encapsulation of AgNPs in polymeric nanofibres. ⁸⁹

Polyvinyl alcohol–chitosan (PVA‐CHI) nanofibres were co‐encapsulated with AgNPs and sulphanilamide for synergistic wound healing. ¹⁰² AgNPs and sulphanilamide hinder water uptake and the swelling of nanofibres, but enhance the antimicrobial effect against gram‐positive and gram‐negative bacteria. In vivo experiments showed similar activity on wound closure in rats. In vivo experiments of PVA–CHI nanofibres and co‐loaded nanofibres on a rat model showed similar activity on wound closure and reached 90.76 ± 4.3% after 1 week compared to the control by 55.26 ± 3.5% after 3 weeks. In another study, PVA–CHI nanofibres were loaded with Ag and Cu NPs, and the antimicrobial assay revealed improved antibacterial properties of AgNP‐loaded nanofibres compared to CuNPs‐loaded nanofibres. ¹⁰³

Ag NPs are used in PVA–pectin nanofibres for wound healing, influencing wound closure rate and providing high antibacterial effects. ¹⁰⁴ The combination of NPs with nanofibres improves mechanical properties, resulting in stronger tensile stress compared to plain nanofibres. For example, polygalacturonic–hyaluronic acid nanofibres were incorporated with AgNPs, and the tensile stress for AgNPs‐loaded nanofibres was reported to be two times stronger than that of plain nanofibres (Figure 3). The study found that the AgNPs component of the nanofibre demonstrated strong antibacterial properties, while the HA component enhanced hydrophilicity and strain activity. ¹⁰⁵

FIGURE 3.

Schematic illustration of the formation of (Ag‐PGA/HA)‐PVA.

So, NP‐embedded polymeric scaffolds have demonstrated great potential to apply as an alternative for conventional wound‐healing dressing. Combination of NPs and nan‐scaffold can improve the characteristics of each of them and solve their limitations.

9. CONCLUSION

In conclusion, the application of NPs, nanofibres and nanosheets in wound healing is a rapidly evolving field with great potential for improving the healing process. These materials offer unique advantages in terms of their ability to deliver bioactive molecules to the wound site, promote tissue regeneration and prevent infection. While much work remains to be done to fully understand the safety and efficacy of these materials, the latest research suggests that they hold great promise for improving wound‐healing outcomes. As such, they are likely to become increasingly important tools in the clinical management of various types of wounds in the coming years.

Overall, the use of NPs, nanofibres and nanosheets represents an exciting new frontier in wound‐healing research and holds tremendous potential for improving the lives of patients with chronic wounds or other types of injuries. By leveraging the unique properties of these nanomaterials, it may be possible to develop novel wound dressings and other biomedical devices, which can provide more effective and targeted therapies for a range of wound‐healing applications. As this field continues to advance, it will be critical to carefully evaluate the safety and efficacy of these materials through rigorous preclinical and clinical studies. With continued research and development, however, these nanomaterials may ultimately transform the way that wounds are treated, providing patients with faster, more effective, and more personalized care.

FUNDING INFORMATION

This research received no external grants or funding from agencies in the public, commercial or not‐for‐profit sectors.

CONFLICT OF INTEREST STATEMENT

The authors declare that there is no conflict of interests regarding the publication of this paper.

Afshar M, Rezaei A, Eghbali S, et al. Nanomaterial strategies in wound healing: A comprehensive review of nanoparticles, nanofibres and nanosheets. Int Wound J. 2024;21(7):e14953. doi: 10.1111/iwj.14953

DATA AVAILABILITY STATEMENT

Data openly available in a public repository that issues datasets with DOIs.