Modern Honey-Based Delivery Systems for Wound Healing: A Review of Current Trends and Future Perspectives

Abstract

Honey is a multifunctional therapeutic agent in wound management with antimicrobial, anti-inflammatory, antioxidant and tissue-regenerative properties. Direct application is limited by high viscosity, variability in composition and instability of bioactive compounds. Advances in biomaterials engineering have enabled the development of honey-based delivery platforms such as nanoparticles, electrospun nanofibers and hydrogels, which improve stability, retention at the wound site and provide controlled release. The review offers a comprehensive overview of honey’s wound-healing mechanisms, evaluates diverse delivery strategies and compares their structural and functional characteristics. Nanoparticles enable targeted delivery and synergistic antimicrobial effects, electrospun mats mimic the extracellular matrix with tunable porosity and hydrogels maintain a moist healing environment with high adaptability. Key challenges include achieving standardization, enhancing mechanical properties and optimizing sterilization methods. Future perspectives emphasize integrating honey-based systems with smart sensors, advanced bioprinting and multifunctional composites to achieve personalized and responsive wound care.

1. Introduction

Chronic and hard-to-heal wounds, including diabetic foot ulcers, venous leg ulcers, and pressure injuries, present a significant clinical and economic burden worldwide. In developed countries, chronic wound management consumes up to 5% of total healthcare budgets, with prevalence expected to rise due to aging populations and the increasing incidence of diabetes and vascular disorders [1,2]. A major barrier to effective wound healing is infection with antibiotic-resistant bacteria up to 80–90% of Staphylococcus aureus strains isolated from wound sites exhibit resistance to penicillin [3]. The emergence of multidrug-resistant (MDR) organisms such as MRSA and Pseudomonas aeruginosa further complicates treatment and delays wound closure [4].

Natural bioactive agents like honey have gained attention for their multifactorial therapeutic potential [5,6,7]. Honey exhibits broad-spectrum antimicrobial effects, including activity against drug-resistant pathogens, in addition to anti-inflammatory and pro-regenerative properties [6,8]. Recent evidence suggests that honey shows particular promise in the treatment of burns, especially superficial and partial-thickness wounds. Compared to silver sulfadiazine (SSD), honey has been associated with faster healing reducing healing time. In this randomized trial of 150 patients with superficial and partial-thickness burns, sites treated with honey healed significantly faster than those treated with silver sulfadiazine (13.5 ± 4.1 vs. 15.6 ± 4.4 days; p < 0.0001) [9]. Complete healing occurred in less than 21 days with honey compared to 24 days with silver sulfadiazine, and P. aeruginosa colonization was lower (6 vs. 27 sites). Additionally, there is some indication that honey may help sterilize wounds more quickly. While the evidence for pressure ulcers is weaker, certain clinical guidelines suggest that medical-grade honey may be considered as a treatment option, albeit with lower-grade recommendations [10]. Specific varieties such as Manuka and Tualang honey have demonstrated efficacy in inhibiting biofilms, modulating immune responses, and accelerating epithelialization. However, despite these advantages, the direct application of honey in wound care presents several challenges, including high viscosity, variability in composition, instability of bioactive compounds, and limited retention at the wound site. These limitations have limited the development of advanced honey-based delivery systems designed to enhance its stability, control its release, and improve bioavailability. Among the most promising platforms are nanoparticles, electrospun nanofibers, and hydrogels, which mimic the extracellular matrix (ECM), maintain a moist healing environment, and provide sustained release of therapeutic agents. Incorporating honey into biopolymer-based platforms further improves its applicability by enhancing mechanical stability, prolonging bioactivity, and facilitating controlled delivery.

In view of the growing clinical demand for multifunctional, biocompatible dressings and recent advances in biomaterials engineering, this review aims to summarize the therapeutic role of honey in wound healing and to highlight recent progress in honey-based delivery systems, with particular emphasis on nanoparticles, electrospun nanofibers, and hydrogels. This narrative review was based on a literature search conducted in PubMed and Google Scholar covering the period 2020–2025. The search strategy combined the terms “honey AND nanoparticles AND wound healing”, “honey AND electrospinning AND wound healing”, and “honey AND hydrogel AND wound healing”. Only full-text articles in English were included. Studies were selected if they addressed the incorporation of honey into advanced delivery systems for wound management or reported relevant biological and therapeutic outcomes. The retrieved evidence was synthesized narratively to summarize current trends and highlight emerging perspectives.

2. Therapeutic Properties of Honey in Wound Healing

Honey has long been recognized for its therapeutic benefits, particularly in wound care. Its effectiveness stems from a combination of biological activities, including antimicrobial action, maintenance of a moist wound environment, stimulation of tissue regeneration, and modulation of the inflammatory response.

2.1. Bioactive Compounds Responsible for Honey’s Therapeutic Properties

The main bioactive compounds that are routinely quantified in honey for biomedical applications are hydrogen peroxide (H₂O₂), methylglyoxal (MGO), bee defensin-1, and the pool of phenolic/flavonoid compounds, and in the case of Manuka honey, dihydroxyacetone (DHA) is additionally measured as the precursor of MGO [11,12]. These molecules are directly responsible for the antimicrobial, antibiofilm, antioxidant, and immunomodulatory activities of honey-based biomaterials. H₂O₂, generated by the enzymatic activity of glucose oxidase upon dilution of honey, is considered the principal factor underlying antibacterial effects in most honeys, although its concentration may vary significantly between samples depending on floral source and storage conditions [13]. In contrast, the unique non-peroxide antibacterial activity of Manuka honey is attributed to its high MGO content, which correlates with clinical efficacy and is used for standardized grading (UMF, MGO index). The UMF index is typically reported in grades such as UMF 5+, 10+, 15+, 20+ and higher, where increasing values correspond to higher methylglyoxal concentrations and stronger non-peroxide antibacterial activity [14]. Bee defensin-1, an antimicrobial peptide of bee origin, contributes additional bactericidal activity and has been linked to stimulation of re-epithelialization [15]. Phenolic and flavonoid compounds, derived from the botanical origin of honey, exert antioxidant activity, modulate reactive oxygen species, and influence inflammatory responses [15,16].

Analytical methods for these bioactives are well established. H₂O₂ is typically determined by peroxidase-based assays, most frequently the horseradish peroxidase/o-dianisidine colorimetric test (HRP) or the more sensitive Amplex Red fluorescence assay [17,18,19]. MGO quantification relies on high-performance liquid chromatography (HPLC) following derivatization with o-phenylenediamine, which forms a stable quinoxaline product, although spectrophotometric methods based on the glyoxalase I pathway have also been applied, and more recently mid-infrared spectroscopy combined with multivariate analysis has been proposed as a rapid, non-destructive alternative for predicting MGO levels and antibacterial potency in honey [20,21]. DHA is similarly determined after derivatization and HPLC separation [22]. Bee defensin-1 is detected through activity-guided fractionation combined with antimicrobial overlay assays and, in more advanced studies, immunodetection techniques [23]. The phenolic fraction is usually characterized by total phenolic content using the Folin–Ciocalteu assay and by antioxidant activity assays such as DPPH or FRAP [24,25]. Although H₂O₂, MGO, defensin-1, and phenolic compounds are considered the principal bioactive constituents of honey, their concentrations exhibit high variability and their stability under physiological conditions is limited; therefore, the biological efficacy of honey-based biomaterials depends not only on the presence of these molecules but also on their preservation, controlled release, and synergistic interactions within the wound environment.

2.2. Antibacterial and Antibiofilm Activity

One of the key attributes of honey is its broad-spectrum antibacterial activity, which extends even to antibiotic-resistant strains such as Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Honey demonstrates potent antibacterial activity against common wound-infecting bacteria [26]. Zone of inhibition (ZOI) values for S. aureus, P. aeruginosa, and E. coli ranged from 13 to 21 mm for Nilgiris honey [27], and from 5.3 to 17 mm across Nigerian honey varieties at 80–100% concentration [28]. Manuka and ulmo honeys inhibited clinical MRSA, E. coli, and P. aeruginosa, with ZOI up to ~38 mm [27,29]. Minimum inhibitory concentration (MIC) values support these findings: Ulmo honey inhibited MRSA at 3.1–6.3% v/v, outperforming Manuka honey (12.5% v/v) [30]. Tualang and Manuka honeys inhibited a wide range of wound pathogens, including MRSA, S. pyogenes, A. baumannii, P. aeruginosa, and E. coli, with MICs ranging from 8.75% to 25% [31]. Nilgiri honey required 25–40% concentrations to inhibit S. aureus, P. aeruginosa, and E. coli [27].

Recent studies have clarified several mechanisms underlying the antimicrobial activity of honey [6]. Hydrogen peroxide is now recognized as the primary contributor to the antimicrobial activity of most honeys, with its concentration strongly correlating with observed MIC and MBC values. The enzyme glucose oxidase (GOx), secreted by honeybees from hypopharyngeal glands during nectar processing, catalyzes the formation of H₂O₂; however, the actual concentration of H₂O₂ in honey varies widely between samples up to 200-fold. Recent studies suggest that factors such as honey’s colloidal structure, presence of polyphenols, and potential microbial or plant-derived GOx may modulate H₂O₂ generation and stability beyond the bee-origin enzyme alone [13]. The high sugar concentration in honey creates a strong osmotic gradient that draws water out of bacterial cells, leading to dehydration and growth inhibition. This hyperosmolar environment not only limits microbial proliferation but also promotes autolytic debridement by attracting lymphatic fluid into the wound [32]. Beyond its well-known osmotic effect and hydrogen peroxide production, specific components such as methylglyoxal (MGO) and the antimicrobial peptide bee defensin-1 have shown notable bactericidal effects [15,33]. These compounds act synergistically to inhibit bacterial proliferation and disrupt biofilm formation, a common complication in chronic wound infections [34,35]. For instance, MGO has been shown to suppress biofilms formed by S. aureus and Pseudomonas aeruginosa, both frequently isolated from infected wound beds [36,37].

2.3. Anti-Inflammatory and Regenerative Effects

Beyond its antimicrobial properties, honey contributes significantly to creating a wound microenvironment conducive to healing. The high sugar concentration, primarily composed of glucose and fructose, exerts a strong osmotic effect that draws lymph fluid from surrounding tissues, helping to maintain a moist wound bed. This environment facilitates autolytic debridement by softening necrotic tissue and promoting the removal of devitalized material through endogenous enzymatic processes [38]. Moisture retention also enables keratinocyte and fibroblast migration, key steps in re-epithelialization and matrix remodeling [39]. Several in vitro and in vivo studies have demonstrated that honey promotes fibroblast proliferation and accelerates re-epithelialization [40,41,42]. In addition, honey has been reported to enhance angiogenesis, a critical component of granulation tissue formation, by upregulating vascular endothelial growth factor (VEGF) expression and promoting endothelial cell proliferation [43,44,45,46]. This angiogenic activity ensures improved oxygen and nutrient delivery to the regenerating tissue, thereby supporting collagen synthesis and overall dermal repair. Figure 1 illustrates the proposed mechanisms of honey in tissue regeneration and the modulation of inflammatory processes.

Moreover, honey stimulates collagen deposition by modulating the activity of fibroblasts and matrix metalloproteinases (MMPs), enzymes involved in extracellular matrix remodeling [47,48]. Histological analyses in wound models have confirmed that honey-treated wounds exhibit more organized collagen fibers and better-aligned epidermal layers compared to untreated controls [49]. Honey has been observed to modulate the local immune response by reducing pro-inflammatory cytokine levels and enhancing the activity of fibroblasts and macrophages—key players in wound remodeling. Its anti-inflammatory action further involves suppression of reactive oxygen species (ROS) generation, inhibition of the complement cascade, and downregulation of COX-2, inducible nitric oxide synthase (iNOS), and matrix metalloproteinase-9 (MMP-9), thereby contributing to a favorable environment for tissue repair [50]. In clinical and preclinical models, honey-based formulations have demonstrated accelerated healing, reduced pain, and improved tissue regeneration, reinforcing its value as a natural component of modern wound dressings [51]. Additionally, honey’s high osmolarity contributes to bacterial cell dehydration, while simultaneously maintaining a moist wound environment conducive to tissue repair [52]. Its acidic average pH value, typically between 3.4 and 6.1 further supports healing by reducing protease activity, which can otherwise degrade newly formed extracellular matrix components [53].

2.4. Therapeutic Honey Types Used in Wound Management

2.4.1. Manuka Honey

Importantly, not all types of honey demonstrate the same therapeutic efficacy. Among the most prominent is Manuka honey, derived from Leptospermum scoparium in New Zealand [54]. Its therapeutic efficacy has been attributed to the high content of methylglyoxal (MGO), which plays a critical role in antibacterial activity [55]. Clinical-grade Manuka honey dressings (e.g., Medihoney^®) are already approved and used in hospital settings [56]. Its efficacy has been demonstrated both in vitro and in vivo, showing enhanced epithelial regeneration, reduced inflammation, and strong biofilm inhibition [57]. Randomized controlled trials have further substantiated the clinical relevance of honey-based dressings. In a multicenter study involving 99 critically ill pediatric patients with stage 1–3 pressure injuries, those treated with medicated Manuka honey dressings showed significantly faster wound healing compared to standard care. The median healing time was reduced from 9 to 7 days, and the likelihood of complete wound closure was nearly doubled (HR 1.86; 95% CI: 1.21–2.87; p = 0.002). Importantly, no allergic reactions or secondary infections were observed in the honey-treated group, underscoring both the efficacy and safety of honey in clinical wound management [58]. A randomized clinical study demonstrated that the application of Manuka honey to third molar extraction sites significantly enhanced socket healing [59]. Participants who received Manuka honey treatment exhibited significantly better healing outcomes by day 7 postoperatively, with only 10.3% showing unhealed sockets compared to 26.8% in the control group (p = 0.029). Moreover, the incidence of socket healing complications, including infection and alveolar osteitis, was notably lower in the honey-treated group (χ² = 4.747; p = 0.029). These findings suggest that local application of Manuka honey may accelerate epithelialization and reduce postoperative complications, reinforcing its role in oral surgical wound management.

2.4.2. Tualang Honey

Another well-documented variety is Tualang honey, sourced from Koompassia excelsa trees in Malaysia [60]. A comparative in vitro study demonstrated that Tualang honey incorporated into Aquacel dressings exerted antibacterial effects against both Gram-positive and Gram-negative bacteria isolated from burn wounds. While its activity was comparable to Manuka honey against Gram-negative pathogens (e.g., Pseudomonas spp., Acinetobacter spp.), it was less effective than Aquacel-Ag and Aquacel-Manuka in inhibiting Gram-positive strains such as Staphylococcus aureus. Nonetheless, Tualang honey showed a reduction in total bacterial load by day 6 and was noted for better handling properties in clinical use [61]. A prospective open-label clinical study demonstrated that oral and topical administration of Tualang honey significantly accelerated postoperative wound healing following tonsillectomy in pediatric patients. By day 14, healing was markedly improved in the honey-treated group compared to controls (p < 0.001 bilaterally), supporting its role as a safe, accessible, and cost-effective adjunct for promoting mucosal recovery after surgery [62]. A randomized controlled trial comparing Tualang honey to steroid-impregnated nasal dressings after endoscopic sinus surgery found that while both treatments produced similar short-term outcomes, the steroid group showed significantly better symptom control and mucosal healing at 3 months (p < 0.05). These findings suggest that Tualang honey may not be as effective as corticosteroids in preventing recurrence and promoting long-term postoperative recovery in sinus surgery patients [63].

2.4.3. Local and Regional Honeys

Local honeys of various botanical and geographical origins have been extensively studied for their wound healing potential, reflecting both accessibility and regional ethnomedical practices. For instance, El-Kased et al. [49] developed chitosan-based hydrogels incorporating Egyptian honey and demonstrated superior antimicrobial and burn healing efficacy at higher honey concentrations, particularly against S. aureus and P. aeruginosa. Similarly, Chopra et al. [64] investigated hydrogel films containing local Indian honey and reported notable in vitro antibacterial activity and favorable moisture management parameters. Regional Nigerian honeys have also been compared by Agbagwa and Frank-Peterside, who tested samples from Western, Southern, Eastern, and Northern Nigeria against clinically relevant pathogens including S. aureus, P. aeruginosa, E. coli, and Proteus mirabilis, showing inhibition zones ranging from 1.4 mm to 17 mm [28]. In another study, Hassanein et al. [65] assessed the MIC values of citrus, clover, Nigella, and Eljabaly honeys against multidrug-resistant burn wound isolates such as Acinetobacter baumannii, Micrococcus luteus, and Cellulosimicrobium cellulans, with inhibitory concentrations as low as 25–30%. Importantly, comparative analysis of Maltese honeys revealed substantial variability in antimicrobial activity depending on floral source and region, highlighting that local honeys may differ greatly in therapeutic efficacy. These findings underscore the clinical relevance of indigenous honeys, which often show comparable bioactivity products like Manuka, while offering practical advantages in terms of cost, availability, and cultural acceptance [66]. Despite promising results, one of the main challenges in the clinical adoption of local honeys lies in the lack of standardization regarding their composition, sterility, and potency, which can limit reproducibility and regulatory approval.

Table 1. Summary of properies.

Honey Type	Botanical/Geographical Origin	Distinct Characterization (Key Bioactives/Markers)	Mechanistic Highlights in Wound Care	Practical Notes/Limitations
Manuka	Leptospermum scoparium (New Zealand)	High methylglyoxal (MGO); also H2O2; bee defensin-1; polyphenols	Strong antibacterial incl. MRSA and biofilms; anti-inflammatory; supports re-epithelialization	Widely available as medical-grade dressings; potency closely linked to MGO; as with all honeys, batch standardization remains important
Tualang	Koompassia excelsa (Malaysia)	Phenolics/flavonoids; H2O2-dependent activity	Antibacterial—particularly strong vs. Gram-negative; anti-inflammatory; supports mucosal healing	Lower activity vs. Gram-positive than some comparators; praised for handling when incorporated in dressings; long-term evidence still developing
Local/regional honeys (e.g., Egyptian, Indian, Nigerian, Maltese, multifloral)	Varies with floral and geographic source	Polyphenols, enzymes; typically H2O2-mediated activity; wide variability across samples	Antimicrobial activity present but ranges widely by origin; supports wound healing via antimicrobial, anti-inflammatory, and moist-environment effects	Major challenge: lack of standardization (composition, sterility, potency); antimicrobial potency varies markedly (e.g., Nigerian honeys ZOI 1.4–17 mm; Maltese honeys vary by floral source)

summarizes types of honey, their botanical and geographical origins, key bioactive markers, proposed mechanisms of action in wound care, and practical considerations or limitations.

2.5. Safety of Honey in Wound Healing

Across clinical studies, medical-grade honey (MGH) dressings demonstrate a generally favorable safety profile when used on appropriately selected wounds and with standard exudate management. In an updated meta-analysis of chronic wound care (8 studies; 906 participants), Tang et al. [67] report that honey dressings accelerated wound-healing time and increased the percentage of wound closure, while safety signals were overall acceptable: there were no statistically significant differences in healing rate, bacterial clearance time, or length of hospital stay versus comparators. Notably, the authors found a nuanced pain signal honey may reduce overall VAS pain scores yet can increase the incidence of “painful discomfort” during treatment, suggesting brief stinging or burning on application despite later analgesic effects as the wound environment stabilizes. The certainty of evidence for safety outcomes was rated very low, driven by risk of bias, inconsistency, and potential publication bias, underscoring the need for adequately powered RCTs with standardized adverse-event capture.

These findings align with earlier evidence in acute wound indications. The Cochrane review concluded that honey heals partial-thickness burns faster than conventional dressings and is associated with a lower overall risk of adverse-events vs. silver sulfadiazine (SSD), though adverse-event reporting quality was often limited [68]. This pattern, acceptable tolerability with some heterogeneity in reporting mirrors the chronic-wound literature and supports the broader safety signal for MGH when used within evidence-based dressing protocols [68]. From a practical standpoint, most reported adverse-events are mild and local (transient stinging/burning at application, occasional periwound maceration in heavily exudative wounds). These risks are typically mitigated by (i) using sterile, medical-grade preparations (to avoid contamination risks inherent to raw honey), (ii) matching dressing Water Vapor Transmission Rate (WVTR)/absorbency to exudate, and (iii) routine periwound skin protection [46]. Allergic reactions to bee products are uncommon in the wound-care literature but should be screened for and documented; in all cases, clinicians should report numerator/denominator adverse-event data and severity grades to improve comparability across trials. Taken together, contemporary evidence supports MGH as well-tolerated in both acute and chronic settings, with the principal safety considerations being transient application discomfort and exudate-related skin maceration manageable with standard wound-care practices.

2.6. Challenges in Clinical Application of Honey

Although honey possesses strong antimicrobial, anti-inflammatory, and tissue-regenerative properties, its direct application in wound care presents several technological limitations. These challenges can significantly impair its clinical effectiveness if not addressed with appropriate formulation strategies.

One major limitation is honey’s high viscosity, which hinders uniform application and may reduce patient comfort and treatment precision [69]. Incorporation of honey into hydrogel matrices has been shown to improve spreadability, moisture retention, and adherence to the wound site, while preserving the bioactive profile of honey. Another key challenge is the instability of honey’s antimicrobial constituents, such as hydrogen peroxide, MGO, and bee defensin-1. These components degrade rapidly under heat, light, or enzymatic activity. Nanoparticle-based systems offer a promising solution by encapsulating honey or its active fractions within polymeric or lipid nanocarriers, allowing controlled release, shielding from degradation, and prolonged bioactivity at the wound interface [70].

Electrospinning has emerged as a particularly good technology for overcoming honey delivery issues. By embedding honey into nanofibrous scaffolds, it is possible to fabricate dressings that mimic the native extracellular matrix, while enabling high surface area-to-volume ratios, controlled porosity, and sustained release of honey’s antibacterial agents [71]. Honey-loaded electrospun nanofibers have demonstrated superior bacterial inhibition, reduced inflammatory response, and accelerated re-epithelialization in preclinical wound models.

3. Advanced Honey Delivery Systems

Although honey possesses a wide spectrum of biological activities beneficial for wound care, including antimicrobial, antioxidant, anti-inflammatory, and pro-regenerative effects, its direct application is often limited by its viscosity, poor retention at the wound site, and uncontrollable release of bioactive compounds. To overcome these challenges, various delivery platforms have been engineered to improve the localization, stability, and sustained release of bioactive components. Among the most prominent are hydrogels, electrospun nanofibers, and nanoparticle-based systems, each offering distinct advantages and limitations (

Table 2. Key features of honey-based wound dressing platforms.

Feature	Nanoparticles	Electrospun Nanofibers	Hydrogels	References
Structure	Dispersed sub-micron particles (spherical or anisotropic)	Continuous fibrous mats (nano- to micro-scale fibers)	Three-dimensional cross-linked hydrophilic polymer networks	[72,73]
Main Components	Metal/metal-oxide or polymeric cores; honey or methylglyoxal as cargo/surface modifier	Natural or synthetic polymers with incorporated honey	Natural or synthetic polymers with incorporated honey	[74,75,76,77]
Release Profile	Burst-to-sustained; governed by particle matrix/coatings and the surrounding medium; often delivered within a secondary carrier	Sustained and tunable; influenced by fiber diameter, porosity and composition	Sustained and tunable; diffusion and network relaxation controlled by crosslink density and water content	[78,79,80,81]
Biocompatibility	Formulation-dependent; ion release and leachables for metal oxides; residual crosslinkers/endotoxin for biopolymers	Generally favorable; depends on polymer choice and residual solvents; low irritation when purified	Generally favorable; depends on polymer and crosslinker chemistry; high water content supports tolerance	[82,83,84,85]
Mechanical behavior	Not load-bearing as a dispersion; mechanical support provided by the host dressing	Moderate to high sheet strength; conformability improved by fiber alignment and basis weight	Soft and elastic; lower tensile strength; stiffness adjustable via crosslinking or reinforcement	[85,86,87]
Moisture Retention	Determined by the host dressing or gel carrier rather than the particles themselves	Moderate water-vapor transmission with in-plane wicking; tunable by layer design	High moisture retention; water-vapor transmission depends on network density and thickness	[88,89]
Form factor and application	Sheet-like, trim-to-size; straightforward placement over wound beds	Sheet-like, trim-to-size; straightforward placement over wound beds	Conformable gels or films; easy to inject or spread over irregular surfaces	[75,88,89]

and Figure 2).

Regardless of the carrier platform used, the common denominator remains the documentation of the sterility of the final product and the stability of the properties after sterilization, the quantification of the honey or methylglyoxal load, the description of the release profile under conditions similar to the wound environment, the reliable measurement of antimicrobial activity and a set of biocompatibility tests compatible with the intended skin and tissue contact. In addition to this core, each of the three platforms requires a set of specific tests derived from the mechanism of delivery of the active substances and the anticipated conditions of use of the dressing.

3.1. Nanoparticle-Based Delivery

The integration of honey into nanoparticle systems has attracted increasing attention in recent years due to its dual function as both a therapeutic agent and a green synthetic medium. Honey contains a complex mixture of reducing sugars (e.g., glucose, fructose), polyphenols, organic acids, and proteins that can serve as natural reductants and capping agents in nanoparticle synthesis. This bioinspired approach enables the fabrication of stable, functional nanomaterials without the use of toxic solvents or surfactants, making it particularly suitable for biomedical applications [90,91,92].

Among various classes of nanoparticles, metal-based and metal oxide nanoparticles such as silver (Ag), iron oxide (Fe₃O₄), zinc oxide (ZnO), and selenium (Se) are of particular interest in wound healing due to their inherent antimicrobial, antioxidant, and anti-inflammatory activities. These properties are critical in the management of chronic or infected wounds, where biofilm formation, oxidative stress, and dysregulated immune responses can significantly delay tissue regeneration. When synthesized or stabilized using honey, these nanoparticles benefit from enhanced biocompatibility, prolonged biological activity, and synergistic effects, resulting in multifunctional platforms for infection control and tissue repair.

In a study by Neupane et al. [93], Himalayan honey was employed as both a reducing and stabilizing agent in the synthesis of iron oxide (Fe₃O₄) nanoparticles. The resulting honey-coated particles exhibited pronounced antioxidant activity in DPPH and FRAP assays and showed dose-dependent antibacterial efficacy against S. aureus and Escherichia coli. The hybrid nanoparticles demonstrated significantly enhanced biological activity compared to free honey or uncoated nanoparticles, with an IC₅₀ value of 0.52 mg/mL in the DPPH assay more than twofold lower than that of free honey. Moreover, the incorporation of honey altered the nanoparticle morphology, producing porous, needle-shaped structures, and contributed to strong inhibition zones, particularly against E. coli, suggesting synergistic effects and potential for wound-related antimicrobial applications.

Similar observations were reported by Shahid et al. [94], who synthesized Fe₂O₃ nanoparticles using Apis mellifera honey, additionally demonstrating notable anti-inflammatory effects. Likewise, silver and copper nanoparticles synthesized in the presence of honey exhibited strong antimicrobial activity and selective cytotoxicity against cancer cell lines, highlighting their therapeutic potential [95,96]. Furthermore, studies on zinc and chromium nanoparticles confirmed their efficacy against antibiotic-resistant bacterial strains and their ability to disrupt biofilms, suggesting their promise as alternatives in combating drug-resistant pathogens [97,98]. An important aspect is the influence of honey type and synthesis conditions on the physicochemical and biological properties of the resulting nanoparticles. As shown by Keskin et al. [99] and Czernel et al. [100], different honey sources (e.g., chestnut, multifloral) and their concentrations directly affect particle size, surface charge, and antifungal efficacy. These findings indicate that honey not only facilitates environmentally friendly nanoparticle synthesis but also imparts unique bioactive properties, making it an attractive component in the development of nanomedicines and treatments for infectious diseases.

Studies on honey-loaded nanoparticles usually emphasize their colloidal characteristics and behavior in media resembling wound exudate. Authors commonly report particle size and distribution, surface charge, and suspension stability, and relate these parameters to the release profile of honey or methylglyoxal and to antimicrobial activity against frequently tested pathogens such as S. aureus and P. aeruginosa. Cytotoxicity assays performed on keratinocytes or fibroblast cell lines are widely used to assess compatibility. In some reports, animal wound models are also employed, which link physicochemical characterization with observable biological outcomes. A broader overview of recent studies on honey-based nanoparticles, including their composition, synthesis methods, and biological activities, is provided in

Table 3. Summary of recent studies on honey-based nanoparticles for wound healing.

Aim of the Study	Material	Methods	Reference
To synthesize iron oxide nanoparticles loaded with Himalayan honey and evaluate their antioxidant and antimicrobial activities.	Composition: iron oxide nanoparticles (IO-NPs) loaded with Himalayan honey (Apis laboriosa), referred to as HHLIO-NPs	In vitro Physicochemical characterization (XRD, SEM, UV-VIS), antioxidant activity (DPPH assay, IC50), antibacterial activity (agar well diffusion against Escherichia coli and Staphylococcus aureus), comparison of activity between HH, IO-NPs and HHLIO-NPs	Neupane et al. [93]
To synthesize copper nanoparticles using honey as a reducing and stabilizing agent, and evaluate their antibacterial and cytotoxic effects.	Composition: copper nanoparticles synthesized with and without honey via ultrasonic irradiation	In vitro Antibacterial activity (MIC50, MBC against E. coli and E. faecalis), cytotoxicity on normal colon cells (CCD112) and colorectal cancer cells (HCT116), physicochemical characterization (UV-VIS, XRD, HRTEM, FESEM-EDX, FTIR), particle size distribution	Ismail et al. [95]
To investigate the anticancer, antimicrobial, and immunomodulatory activities of silver nanoparticles synthesized using two types of honey	Composition: silver nanoparticles synthesized using Sider and Dharm honey as reducing agents (green synthesis)	In vitro Cytotoxicity (on MCF-7, HepG2, HCT-116, A-549 cancer cell lines), antimicrobial activity (agar well diffusion against E. coli, S. aureus, P. aeruginosa, C. albicans), immunomodulatory activity (phagocytic index in mice macrophages), physicochemical characterization (UV-VIS, FTIR, SEM)	Ghramh et al. [96]
To compare gold nanoparticles synthesized with honey and with citrate in terms of their colloidal behavior, protein interactions, and cytotoxicity.	Composition: gold nanoparticles synthesized via green method with honey (AuNPs@honey) and via Turkevich method with citrate (AuNPs@citrate)	In vitro Nanoparticle stability in cell media, protein corona formation, cytotoxicity (L929 fibroblasts, B16 melanoma), ROS generation, apoptosis induction	Boldeiu et al. [101]
To synthesize iron oxide (Fe2O3) nanoparticles using honey from Apis mellifera as a green reducing and capping agent, and to evaluate their antibacterial, antioxidant, and anti-inflammatory properties.	Composition: Iron oxide nanoparticles (Fe2O3-NPs) synthesized via green method using Apis mellifera honey as reductant and stabilizer	In vitro Physicochemical characterization (UV-Vis at 350 nm, XRD, SEM, EDX, ICP-MS, VSM), antibacterial activity (inhibition zones, MIC against clinical isolates of Klebsiella pneumoniae), antioxidant activity (IC50 = 22 µg/mL), anti-inflammatory activity (IC50 = 70 µg/mL)	Shahid et al. [94]
To biosynthesize silver nanoparticles using aqueous honey at various concentrations and evaluate their antifungal efficacy against Candida albicans and Candida parapsilosis.	Composition: Silver nanoparticles (AgNPs-C for citrate, AgNPs-H2, H10, H20 for 2%, 10%, 20% honey-mediated synthesis)	In vitro Physicochemical characterization (UV–Vis, fluorescence spectroscopy, SEM, DLS including size, zeta potential), antifungal activity (MIC determination, disk diffusion assay against C. albicans and C. parapsilosis), effect of honey concentration on synthesis	Czernel et al. [100]
To synthesize chromium oxide nanoparticles using honey as a reducing agent and evaluate their antioxidant and antibacterial properties.	Composition: Chromium oxide nanoparticles (Cr2O3 NPs) synthesized by reduction of potassium dichromate using natural honey	In vitro Physicochemical characterization (UV–Vis, FT-IR, XRD, SEM, EDAX, AFM), total antioxidant activity (phosphomolybdenum method), antibacterial activity (zone of inhibition against E. coli, Bacillus spp., and S. aureus)	Nivethitha et al. [97]
To synthesize AgNPs using chestnut honey as reducing and stabilizing agent and to evaluate their antioxidant, antibacterial, and enzyme inhibition properties.	Composition: silver nanoparticles (CH-AgNPs) synthesized with Castanea sativa (chestnut) honey at 30, 60, 90 °C	In vitro Physicochemical characterization (UV-Vis, FT-IR, SEM, EDX, DLS), antioxidant activity (DPPH assay), antibacterial activity (MIC, inhibition zones against various bacteria), enzyme inhibition	Keskin et al. [99]
To evaluate antimicrobial, immunomodulatory, and cytotoxic activities of silver and selenium nanoparticles synthesized using Acacia honey and Calotropis procera leaf extract.	Composition: Silver (AgNPs) and selenium (SeNPs) nanoparticles synthesized using Acacia honey and Calotropis procera leaf extract	In vitro Physicochemical characterization (UV–Vis, TEM, SEM, FTIR, XRD), antimicrobial activity (disk diffusion assay against S. aureus, B. subtilis, E. coli, P. aeruginosa, C. albicans), immunomodulatory activity (phagocytic index in mice macrophages), cytotoxicity (MTT assay on HepG2 and HCT116 cell lines)	Ghramh et al. [102]
To synthesize zinc oxide nanoparticles using honey as a green reductant and evaluate their antibacterial, antibiofilm, antioxidant, and membrane-damaging activity against multidrug-resistant clinical bacterial strains.	Composition: zinc oxide nanoparticles (ZnONPs) synthesized by auto-combustion method using natural honey as reducing and stabilizing agent	In vitro Physicochemical characterization (UV–Vis, FTIR, XRD, FE-SEM, TEM, DLS, zeta potential), antioxidant activity (DPPH, ABTS assays), antibacterial activity (against K. pneumoniae, E. coli, MRSA, P. aeruginosa, S. aureus), antibiofilm activity, membrane integrity analysis (leakage of nucleic acids and proteins)	Atapakala et al. [98]
To synthesize decahedral cinnamon nanoparticles (DCNPs) in honey using pulsed laser ablation in liquid (PLAL) and to evaluate their antibacterial activity against Gram-negative and Gram-positive bacteria.	Composition: cinnamon nanoparticles synthesized from solid cinnamon sticks in 5 mL honey solution using pulsed laser ablation (Nd:YAG laser at 1064 nm, 30–180 mJ)	In vitro Nanoparticle morphology (HR-TEM, EDX), FTIR spectroscopy, antibacterial activity (agar well diffusion, optical density OD600) against E. coli and B. subtilis, dependence of antibacterial effect on laser ablation energy	Salim et al. [103]

, which summarizes in vitro and in vivo findings across a wide range of nanoparticle types and therapeutic targets.

3.2. Electrospun Honey-Based Nanofibers

Electrospinning is a well-established technique for producing fibers from polymer solutions using electrostatic forces. The resulting nanofibrous mats exhibit high porosity, large surface area-to-volume ratios, and structural resemblance to the extracellular matrix (ECM), making them highly suitable for wound healing applications. The incorporation of honey into electrospun scaffolds enables the convergence of natural bioactivity with controlled delivery platforms, addressing key limitations of raw honey use such as rapid diffusion, instability, and unstandardized dosing.

Numerous studies have demonstrated that the addition of honey significantly influences fiber morphology, surface characteristics, and biological performance. For example, Arslan et al. [104] specifically investigated how honey and chitosan affect the electrospinning of PET-based mats, with a focus on fiber uniformity and water uptake capacity. They reported that honey enhanced fiber uniformity, reduced fiber diameter, and increased deposition area. These mats also exhibited high water uptake capacities (280–430%) and reached hydration equilibrium within 15 min, supporting the maintenance of a moist wound environment. The effect of honey concentration on cellular responses and inflammation has also been explored. Minden-Birkenmaier et al. [105] showed that electrospun mats containing different concentrations of Manuka honey (0.1%, 1%, and 10%) inhibited neutrophil extracellular trap formation (NETosis) and suppressed MMP-9 release. In contrast, 10% honey increased pro-inflammatory activity, indicating the existence of a therapeutic window for honey incorporation [105]. To combine honey’s bioactivity with anti-inflammatory drugs, Maleki et al. [106] developed PVA/honey nanofibers loaded with dexamethasone. Fibers were uniform and bead-free up to 30% honey content; however, higher concentrations led to spindle-like bead formation. Although a burst release of dexamethasone was observed, the presence of honey did not significantly alter the drug release kinetics.

The work by Sarhan and Azzazy [107] demonstrated that higher honey content can yield potent antimicrobial effects while maintaining cytocompatibility. They developed PVA/chitosan/honey nanofibers containing up to 40% honey and 5.5% chitosan. The scaffolds displayed adjustable morphology and swelling behavior, complete inhibition of S. aureus within 48 h, and excellent cytocompatibility with primary fibroblasts, highlighting their potential for antimicrobial wound treatment. Adding inorganic nanoparticles is another strategy to achieve multifunctionality. Abolhassani et al. [108] investigated polyurethane/gelatin nanofibers loaded with honey and ZnO nanoparticles. The resulting composites demonstrated significantly enhanced antibacterial activity against E. coli, S. aureus, and B. subtilis, improved mechanical strength, and promoted HEK cell proliferation, supporting their multifunctional properties for wound healing applications.

Similarly, hybrid systems combining honey with plant extracts have been tested to achieve synergistic effects. Jawad et al. [109] developed a composite system of PVA/chitosan loaded with honey, clove essential oil, and Al₂O₃ nanoparticles. These scaffolds exhibited potent antibacterial activity against S. aureus and enhanced fibroblast migration in scratch wound assays. Similarly, Uddin et al. produced biodegradable electrospun PVA mats enriched with honey, garlic extract, Nigella sativa, and olive oil. The nanofibers were smooth and uniform (150–170 nm in diameter) and showed strong antibacterial properties and cytocompatibility [110].

Several in vivo studies have confirmed that honey-loaded electrospun mats not only perform well in the lab but also accelerate wound healing in animal models. In vivo studies have further confirmed the regenerative potential of honey-loaded nanofibers. Gashti et al. [111] developed poly(diallyldimethylammonium chloride) (PDDA)/honey nanofibrous mats (50/50 and 40/60) that accelerated wound closure in diabetic rats, reaching 94% healing by day 12 (murine model). These scaffolds also exhibited sustained compound release over 125 h, reduced inflammation, and enhanced collagen deposition. Kheradvar Kolour et al. [112] designed a Janus wound dressing composed of an electrospun gelatin/PCL nanofiber layer combined with a gelatin/honey/curcumin hydrogel layer. The bilayer structure demonstrated excellent mechanical properties (tensile strength ~40 MPa), high swelling capacity (~800%), and promoted effective wound healing and tissue regeneration in full-thickness wounds in rats, outperforming commercial dressings.

Studies highlight the promising role of electrospun honey-based nanofibers in wound care. The electrospinning process not only enables structural biomimicry of ECM but also facilitates sustained and localized delivery of honey’s bioactives. The trend toward multifunctional systems combining honey with antibacterial, anti-inflammatory, and pro-angiogenic agents opens new avenues for addressing complex and chronic wounds. Electrospun nanofiber mats are typically described in terms of their morphology and mechanical performance. Scanning electron microscopy is used to present fiber diameters, alignment, porosity, and overall mat thickness, while tensile strength and elongation at break are reported to indicate durability and handling properties. Studies also provide data on water vapor transmission rate and fluid absorption, which are considered relevant for comfort and safe use on exudative wounds. The effect of sterilization procedures on nanofiber structure and on the release of honey is another recurring point of interest, reflecting concerns about stability during processing and storage. The diversity of approaches, materials, and outcomes achieved with honey-loaded electrospun nanofibers is summarized in

Table 4. Literature overview of electrospun nanofibers incorporating honey.

Aim of the Study	Material	Methods	Reference
To evaluate the effect of honey and chitosan on the electrospinning process and structural properties of PET-based fibrous mats for potential use in wound dressings	Electrospun PET, PET/chitosan, and PET/honey fibers with 10–40% honey	In vitro Fiber morphology, fiber diameter, water uptake, wettability, porosity, and cytotoxicity (L929 fibroblasts)	Arslan et al. [104]
To evaluate the effect of Manuka honey incorporated into electrospun tissue engineering templates on neutrophil extracellular trap formation (NETosis), aiming to modulate inflammatory responses and reduce MMP-9 release.	Electrospun polydioxanone (PDO) with 0–10% Manuka honey	In vitro Fiber morphology, honey release, NETosis (fluorescence + MPO), MMP-9 and cytokine release	Minden-Birkenmaier et al. [105]
To fabricate electrospun polyurethane/gelatin nanofibers loaded with honey and ZnO nanoparticles and evaluate their antibacterial, mechanical, and cytotoxic properties for wound dressing applications	Electrospun PU/Gel nanofibers with 10% honey and 1% ZnO nanoparticles	In vitro Fiber morphology, mechanical properties (tensile strength, elongation), antibacterial activity (E. coli, S. aureus, B. subtilis), and cytotoxicity (MTT assay on HEK cells)	Abolhassani et al. [108]
To develop high-concentration honey–chitosan–PVA nanofibers with dexamethasone and evaluate their potential as biocompatible wound dressings.	Electrospun PVA/honey nanofiber meshes (ratios 100/0 to 60/40) ± 5/10/15% of dexamethasone	In vitro Fiber morphology, diameter, presence of beads, drug (dexamethasone) release profile, burst release dynamics	Maleki et al. (2013) [106]
To develop and evaluate electrospun PVA/chitosan/honey nanofibers with different compositions for potential use as wound dressings, focusing on fiber morphology, mechanical properties, antimicrobial activity, and biocompatibility.	Electrospun PVA/chitosan/honey nanofibers (ratios: PVA/chitosan 7/1.5–7/3.5, PVA/honey 10/20–10/30, honey/PVA/chitosan 30/7/1.5–40/7/3.5 crosslinked (glutaraldehyde vapor + thermal/freeze–thaw))	In vitro Fiber morphology (SEM), FTIR spectroscopy, swelling and degradation behavior, tensile strength, antibacterial activity (S. aureus, E. coli), cytotoxicity (MTT assay on human fibroblasts), crosslinking (glutaraldehyde vapor, freezing/thawing, heating)	Sarhan et al. [107]
To optimize electrospinning parameters for honey/betel-loaded PCL/chitosan nanofibrous scaffolds and evaluate their morphology, physicochemical, mechanical, and biological properties for tissue engineering applications	Electrospun scaffolds of 12% w/v PCL with honey and betel, blended with 2% chitosan (PCL:honey/betel:chitosan, 2:7 ratio and crosslinked via glutaraldehyde vapor)	In vitro Electrospinning optimization, fiber morphology (bead-free, random), hydrophilicity (contact angle), thermal behavior (DSC), mechanical strength (tensile), degradation, cell viability (PBMC), and hemocompatibility	Adhikari et al. [113]
To fabricate pine honey-loaded electrospun poly(vinyl alcohol)/gelatin nanofibers and evaluate their structural and antioxidant properties	Electrospun PVA/gelatin nanofibers loaded with 0–15% pine honey	In vitro Fiber morphology (SEM), diameter, wettability (contact angle), FTIR, and antioxidant activity (DPPH, ABTS, β-carotene-linoleic acid, CUPRAC)	Parin et al. [114]
To create a dual-layer wound dressing by electrospinning gelatin/honey biopolymer solutions	Electrospun gelatin/honey biopolymer solution applied as a dual-layer dressing on cotton gauze (gelatin:honey ratios from 95:5 to 70:30)	In vitro Fiber morphology (bead formation, diameter), hydrophobicity (contact angle), chemical integration (FTIR), and potential for dermal applications	Azizabad et al. [115]
To develop electrospun EC/gum tragacanth nanofibers with varying honey concentrations and evaluate their physicochemical and biological properties for wound dressing applications.	Electrospun ethylcellulose/gum tragacanth nanofibers loaded with 5–20% w/w multifloral honey	In vitro Fiber morphology (bead-free, smooth), honey release profile, antioxidant capacity, cytotoxicity	Ghorbani et al. [116]
To fabricate electrospun PLA scaffolds incorporating Manuka honey and SNAP for dual antibacterial and regenerative functionality.	Electrospun PLA nanofibers co-loaded with Manuka honey and SNAP (a nitric oxide donor)	In vitro Fiber morphology, sustained nitric oxide release, tensile strength, wettability, water retention, water vapor transmission, antibacterial activity (against S. aureus and E. coli), and fibroblast attachment/proliferation	Ghalei et al. [117]
To develop electrospun PCL–methylcellulose mats functionalized with Manuka honey and bioactive glass for wound dressing applications	Electrospun PCL/methylcellulose fiber mats cross-linked with Manuka honey and loaded with bioactive glass (BG) particles	In vitro Fiber morphology and chemistry (SEM, FT-IR), wettability, mechanical strength (3–5 MPa), bioactivity (simulated body fluid tests), fibroblast and HaCaT cell proliferation and migration, antibacterial activity	Schuhladen et al. [118]
To fabricate electrospun PVA/chitosan/collagen nanofibers with honey and evaluate their antibacterial, mechanical, and biological properties for wound dressing applications.	Electrospun nanofibrous membranes from polyvinyl alcohol (PVA), chitosan, collagen, and honey at 0%, 5%, 10%, and 15% honey concentrations	In vitro Fiber morphology (diameter, porosity), water vapor transmission rate (WVTR), adsorption, mechanical properties (elastic modulus, elongation), antibacterial efficacy (against S. aureus, P. aeruginosa, E. coli, L. monocytogenes), and biocompatibility (cytotoxicity, fibroblast and keratinocyte viability)	Servín de la Mora-López et al. [119]
To develop electrospun PVA nanofibers incorporating Nigella sativa, honey, garlic, and olive oil, and evaluate their antibacterial and biological performance for wound dressing use.	Electrospun PVA nanofibers co-loaded with 3 mL Nigella sativa extract, 2 mL honey, 2 mL garlic extract, and 2 mL olive oil (per 20 mL PVA solution)	In vitro Fiber morphology, thermal stability, antibacterial activity (S. aureus), moisture absorption, cytocompatibility	Uddin et al. [110]
To fabricate electrospun PVA nanofibers co-loaded with honey and turmeric extract, and assess their structural and antimicrobial properties for wound care applications	Electrospun PVA nanofibers containing honey and Curcumin longa extract (CL-1: 20 mL PVA + 10 mL honey + 1 g turmeric; CL-2: same with 2 g turmeric)	In vitro Fiber morphology (SEM), moisture management, FTIR chemical composition, and antibacterial activity against S. aureus	Shahid, Ali. [120]
To fabricate electrospun PVA fibers with glycerin and honey and evaluate their morphology and polymer integration	Electrospun composite fibers from 10% PVA solution containing 1% v/v glycerin and 1% v/v multifloral honey	In vitro Fiber morphology, glycerin-induced plasticity, and incorporation efficiency of honey (FTIR, SEM)	Arianto et al. [121]
To develop Layer-by-Layer-coated PCL membranes with Manuka honey, chitosan, and essential oils for antibacterial wound dressing.	Electrospun PCL membranes functionalized by Layer-by-Layer assembly with 16 alternating layers of 20% (w/v) Manuka honey (MH) and 1% (w/v) chitosan, plus 4 additional spray layers containing cinnamon or tea tree essential oil (EO)nanoemulsions (EO:MH ratio 1:15)	In vitro Fiber morphology (SEM), chemical composition (XPS, FTIR), EO/MGO release, fibroblast viability and gene expression (VEGF, COL1, TGF-β1), antibacterial activity against S. aureus and P. aeruginosa	Gallo et al. [122]
To fabricate crosslinked PVA/chitosan/honey membranes and assess their mechanical, structural, and antibacterial performance.	Solution-cast membranes composed of 1.80 g PVA, 0.3 g chitosan, and honey at 1%, 5%, 10%, and 15% w/w (0.35 g, 1.75 g, 3.5 g, and 5.25 g, respectively), crosslinked with glutaraldehyde	In vitro Crystallinity (XRD), chemical structure (FTIR), surface morphology (SEM, AFM), mechanical strength and elongation, wettability (contact angle), swelling behavior, and antibacterial activity against E. coli and S. aureus	Radoor et al. [123]
To create silk fibroin/PCL bilayer nanofibrous membranes with Manuka honey for skin-related wound healing.	Electrospun nanofibers composed of silk fibroin (SF), polycaprolactone (PCL), and Manuka honey	In vitro Fiber morphology (SEM), mechanical properties (stress, flexibility), hydrophilicity (for cell adhesion), antibacterial activity (S. aureus, E. coli, C. albicans), cytocompatibility (cell proliferation/adhesion)	Lan et al. (2021) [124]
To compare the antibacterial efficacy and biocompatibility of natural clove extract and aluminum oxide nanoparticles incorporated into honey/chitosan-based nanofibrous wound dressings	Electrospun nanofibers prepared from 15% honey, 10% chitosan, 5% TPP, optionally 13% clove extract and 3% Al2O3 nanoparticles, dissolved in 1% HCl	In vitro Fiber morphology, antibacterial efficacy (S. aureus, E. coli), in vitro wound healing (fibroblast scratch assay), and nanoparticle distribution	Jawad et al. [109]
To fabricate alginate/PVA nanofibers with honey and assess their antioxidant, antibacterial, and cytocompatibility features.	Electrospun nanofibers composed of 7.2% PVA and 0.8% alginate with 0%, 5%, 10%, 15%, and 20% (v/v) acacia honey, crosslinked with glutaraldehyde	In vitro SEM (fiber morphology), FTIR (chemical structure), swelling ratio, weight loss, DPPH assay (antioxidant), antibacterial activity (disk diffusion and dynamic contact), cytotoxicity (MTT), cell adhesion (light microscopy)	Tang et al. [125]
To develop PVP nanofibers with honey and iodine and evaluate their synergistic antibacterial properties.	Electrospun PVP fibers containing 2% v/v honey and 0–5% w/v iodine	In vitro Fiber morphology (SEM), chemical composition (FTIR), thermal stability (TGA), fiber diameter changes (decrease with iodine, increase with honey), and antibacterial efficacy against S. aureus and E. coli	Khanzada et al. [126]
To fabricate multilayer electrospun PVA wound dressings with honey and curcumin and assess their antioxidant and antibacterial activity.	Electrospun nanofibers composed of 6% (w/v) PVA, 6% (w/v) honey, and/or 1% (w/v) curcumin; plus 16% cellulose acetate + 1% curcumin solution in acetone:DMAc (2:1)	In vitro Fiber morphology, chemical compatibility (FTIR), water absorption, water vapor transmission rate (MVTR), contact angle antioxidant activity, and antibacterial activity against E. coli	Gaydhane et al. (2020) [127]
To fabricate crosslinked PDDA/honey nanofibers and assess their fluid uptake, antibacterial performance, and diabetic wound healing in vivo.	Electrospun nanofibers composed of PDDA with 50% and 60% (w/w) Manuka honey; mixed with ethanol to 5 mL total volume; crosslinked with glutaraldehyde	In vitro and in vivo SEM (fiber morphology), FTIR (chemical structure), contact angle (surface wettability), swelling and degradation analysis, tensile strength (mechanical testing), antibacterial activity (S. aureus, E. coli—zone of inhibition, bacterial adhesion), in vivo wound healing in mice (wound closure measurement, H&E histological analysis)	Gashti et al. [111]
To create PVP-based nanofibers with Manuka honey and titanate nanotubes and evaluate their healing effects in vivo.	Electrospun nanofibers composed of 15% (w/v) polyvinylpyrrolidone (PVP) and 15–25% (v/v) Manuka honey; combined with chitosan–titanate hybrid prepared from 2.5% (w/v) chitosan and 2.5% (w/v) titanium dioxide nanotubes (TiONTs) in acetic acid, crosslinked via glutaraldehyde vapor	In vitro and in vivo SEM (fiber morphology), FTIR and XRD (structure), mechanical strength (tensile test), water contact angle, MGO release, antibacterial activity (S. aureus, E. coli), in vivo wound healing in rats (macroscopic wound closure, histology with re-epithelialization markers)	Kassem et al. [128]
To fabricate chitosan/honey nanofibers with capsaicin and/or gold nanoparticles and assess their antibacterial and healing efficacy in rabbits.	Electrospun mats based on 25% (w/v) honey, 3% (w/v) chitosan, and 8% (w/v) tripolyphosphate (TPP); variants include addition of 1 mg/mL capsaicin and 10% (v/v) gold nanoparticles (AuNPs)	In vitro and in vivo Nanofiber morphology, viscosity, antibacterial activity (against P. multocida, K. rhinoscleromatis, S. pyogenes, V. vulnificus), cytotoxicity and cell proliferation (Vero fibroblasts), and wound-closure efficacy (In vivo (rat full-thickn ess dorsal wounds))	Al musawi et al. [129]
To develop a bilayer electrospun/hydrogel gelatin-based scaffold containing honey and curcumin for enhanced wound healing, and evaluate its in vivo performance compared to commercial dressings	Bilayer scaffold: enzymatically cross-linked gelatin hydrogel loaded with honey and curcumin (bottom layer), reinforced with gelatin/polycaprolactone (PCL) electrospun nanofibers (top layer)	In vitro and in vivo Mechanical properties (tensile strength, elongation), swelling rate, water vapor permeability, MTT cytocompatibility, histopathology (collagen deposition, granulation, immune response, re-epithelialization), and wound closure rate	Kheradvar Kolour et al. [112]
To design a bilayer dressing of honey sponge and VEGF/keratin-loaded nanofibers and assess their angiogenic and regenerative capacity.	Bilayer scaffold: top layer—sponge of poly(acrylic acid) (PAAc) with honey (Hny); bottom layer—electrospun nanofibers of keratin (Kr), honey (Hny), and vascular endothelial growth factor (VEGF), forming PAAc–Hny/Hny–Kr–VEGF system	In vitro and in vivo (Morphology (SEM), VEGF release (7 days), mechanical strength, cytocompatibility (keratinocytes), angiogenesis (CAM), wound closure, blood vessel formation, collagen synthesis, re-epithelialization)	Tavakoli et al. [130]
To develop polycaprolactone (PCL) nanofibrous membranes incorporating stingless bee honey and curcumin for wound healing, and to evaluate their physicochemical, antibacterial, and biological performance	Electrospun nanofibers made from 12% (w/v) polycaprolactone (PCL) solution with stingless bee honey and curcumin; optimized blend mixed with 2% (w/v) chitosan in formic acid:acetone (4:6) solvent (CS:PCL ratio 2:7)	In vitro and in vivo SEM (morphology), ATR-FTIR (functional groups), DSC (thermal properties), tensile strength test, water degradation, contact angle (hydrophilicity), in vitro cytotoxicity (MTT on PBMCs), hemocompatibility, in vivo wound healing in rats (histology and closure rate)	Samraj et al. [131]

, offering a concise reference for fiber compositions, characterization methods, and antibacterial or regenerative performance.

3.3. Honey-Based Hydrogels

Hydrogels are three-dimensional, hydrophilic polymeric networks capable of retaining large amounts of water or biological fluids while maintaining structural integrity. Their high moisture content, softness, and tunable mechanical properties make them particularly attractive for wound healing applications, where maintaining a moist environment, supporting cell migration, and facilitating gas exchange are critical. Hydrogels, due to their tunable physicochemical properties, biocompatibility, and capacity for controlled drug delivery, represent promising materials in emergency therapy, particularly for rapid hemostasis, wound management, and tissue repair [132]. Natural and synthetic polymers such as chitosan, alginate, gelatin, hyaluronic acid, and poly(vinyl alcohol) are frequently employed in hydrogel fabrication due to their biocompatibility and biodegradability [133,134]. These materials can be physically or chemically crosslinked and further modified to incorporate active agents such as antimicrobial compounds, growth factors, or plant-derived substances, enhancing their therapeutic value [135].

Honey-based formulations have been widely explored for their therapeutic applications in wound healing, often developed in the form of hydrogels or dried films, depending on the intended use and desired release characteristics. These systems are frequently constructed from natural biopolymers such as chitosan, alginate, gelatin, or pectin, which offer inherent biocompatibility and biodegradability [133]. When combined with honey, these materials benefit from honey’s well-documented antimicrobial, antioxidant, and anti-inflammatory properties. For instance, El-Kased et al. [49] demonstrated that chitosan-based hydrogels containing 75% honey significantly outperformed commercial treatments in a murine burn model, indicating both enhanced antibacterial activity and accelerated tissue regeneration. Similarly, other studies have sought to optimize mechanical stability, swelling behavior, and controlled release, tailoring hydrogels for specific wound healing needs. Shamloo et al. [136] and Koosha et al. [137] developed physically crosslinked systems using chitosan/PVA and gelatin, which showed improved structural integrity and promoted cellular infiltration, supporting honey’s role in modulating the wound microenvironment. Another line of research focuses on mimicking honey’s natural antibacterial pathways. Giusto et al. [138] formulated a pectin-honey film, highlighting its anti-inflammatory potential and favorable cytokine profile in vivo. Studies by Vasques et al. [139] and Mitchell et al. [140] emphasized that mimicking honey’s hydrogen peroxide-mediated antibacterial mechanism or combining honey with cryogel matrices can produce potent antibacterial scaffolds effective even against resistant strains like MRSA. Moreover, dual-crosslinked structures (e.g., Mukhopadhyaya et al. [141]) and hybrid matrices incorporating nanomaterials or drug carriers (e.g., Stojkovska et al. [70], Jha et al. [142]) further underscore honey’s versatility as a therapeutic adjuvant. These findings collectively suggest that the bioactivity of honey can be retained or even enhanced when incorporated into diverse natural polymeric platforms, reinforcing its value in multifunctional wound dressing strategies. Importantly, the use of natural components not only supports biocompatibility but also aligns with growing interest in sustainable, bio-derived materials for regenerative medicine.

Formulations range from borax-crosslinked PVA gels for controlled drug release [103] to dual-network chitosan–PVA systems with improved mechanical strength. Quaternized chitosan (QCS) was blended with pectin (Pec) to improve water solubility and antibacterial activity of the hydrogel films [143]. Propolis was also loaded into hydrogel films to improve wound healing ability. Therefore, the aim of this study was to fabricate and characterize the propolis-loaded QCS/Pec hydrogel films for use as wound dressing materials. The morphology, mechanical properties, adhesiveness, water swelling, weight loss, release profiles, and biological activities of the hydrogel films were investigated. Scanning Electron Microscope (SEM) investigation indicated a homogenous smooth surface of the hydrogel films. The blending of QCS and Pec increased tensile strength of the hydrogel films. Moreover, the blending of QCS and Pec improved the stability of the hydrogel films in the medium and controlled the release characteristics of propolis from the hydrogel films. The antioxidant activity of the released propolis from the propolis-loaded hydrogel films was ~21–36%. The propolis-loaded QCS/Pec hydrogel films showed the bacterial growth inhibition, especially against S. aureus and S. pyogenes. The propolis-loaded hydrogel films were non-toxicity to mouse fibroblast cell line (NCTC clone 929) and supported the wound closure. Therefore, the propolis-loaded QCS/Pec hydrogel films might be good candidates for use as wound dressing materials.

Beyond the examples described above, numerous additional studies (summarized in

Table 5. Selected studies on honey-based hydrogels for wound care applications.

Aim of the Study	Material	Methods	Reference
To develop honey–PVA hydrogels crosslinked with borax for wound dressing applications and evaluate their mechanical, antimicrobial, and antibiotic-release properties	Hydrogels composed of PVA and 60% honey (v/v) with varying concentrations of borax (0–3% w/v) as crosslinker	In vitro Morphology (SEM), swelling kinetics, permeability, bioadhesion, mechanical strength (tensile test), cytotoxicity (fibroblasts), antibacterial activity (S. aureus, E. coli), amoxicillin release profile	Tavakoli et al. [144]
To develop chitosan/PVA hydrogel films incorporating honey via solvent-casting and evaluate their potential as wound dressings	Hydrogel films from chitosan (0.25–2%), PVA (5% w/v) and local honey (variable proportions)	In vitro Thickness, weight variation, folding endurance, moisture content, moisture uptake, WVTR, swelling, morphology (SEM), interactions (FTIR, DSC); In vitro honey release, antimicrobial activity (S. aureus), in silico docking of honey compounds;	Chopra et al. [64]
To create an injectable, fast-forming hydrogel that mimics honey’s antimicrobial hydrogen peroxide release for treating bacterially colonized wounds	Hydrogel formed via thiol-ene click chemistry between hyperbranched PEGDA (10% w/w) and thiolated hyaluronic acid (1% w/w), loaded with glucose oxidase (0–500 U/L) and 2.5% w/w glucose to simulate honey-like H2O2 production	In vitro Gelation time, swelling, stability, H2O2 release, cytocompatibility (L929, HaCaT), antibacterial activity (MRSA, MRSE, S. aureus, E. coli, P. aeruginosa, A. baumannii)	Vasquez et al. [139]
To develop hybrid hydrogel scaffolds combining Manuka honey with 2-hydroxyethyl methacrylate (HEMA) and gelatin, and to investigate their suitability for tissue regeneration applications	Scaffolds made from HEMA and gelatin with Manuka honey at three concentrations: 10%, 20%, and 30% (w/w)	In vitro Porosity, pH- and temperature-dependent swelling, in vitro degradation, biocompatibility (MTT assay on MRC-5 and HaCaT)	Tomić et al. [145]
To evaluate how Manuka honey incorporation into chitosan–gelatin cryogels and hydrogels enhances antibacterial efficacy and scaffold properties	Cryogel and hydrogel scaffolds composed of chitosan:gelatin (1:4) doped with 0%, 1%, 5% or 10% Manuka honey	In vitro SEM, swelling capacity, pore size, bacterial clearance (S. aureus), biofilm formation, cytotoxicity/cellular infiltration (likely fibroblasts or relevant cell lines)	Mitchell et al. [140]
To develop honey-based nanocomposite hydrogels with enhanced antimicrobial activity against multi-resistant pathogens for wound healing applications	Hydrogel matrix composed of honey, alginate, and nanocrystalline cellulose (NCC), with silver nanoparticles (AgNPs) synthesized in situ from honey and silver nitrate	In vitro Antibacterial activity (disk diffusion, MIC/MBC against A. baumannii, P. aeruginosa, S. aureus), morphology (SEM), EDX for Ag distribution, FTIR, XRD, water content, stability, biocompatibility (human dermal fibroblasts)	Stojkovska et al. [70]
To develop a multifunctional PVA/chitosan/honey/clay hydrogel with responsive properties for enhanced wound healing	Hydrogel composed of 10% PVA, 1.5% chitosan, 1% honey, 2% clay (montmorillonite)	In vitro Water absorption, swelling behavior, WVTR, mechanical properties (tensile strength, elongation), cytocompatibility (MTT), antibacterial activity (S. aureus, E. coli)	Noori et al. [146]
To develop and evaluate a pectin-honey hydrogel (PHH) as a wound healing membrane and compare its effect with pectin hydrogel and liquid honey	Hydrogel composed of Manuka honey and citrus pectin (1:1 v/v with water, then pectin added)	In vivo (Sprague Dawley rats model) Wound area reduction rate, histological evaluation (inflammation, re-epithelialization, fibrous tissue), wound contraction	Giusto et al. [147]
To develop sodium alginate hydrogel films incorporating honey and red cabbage-derived anthocyanins as pH-sensitive, antibacterial, and antioxidant wound dressings	Films composed of 8% (w/v) sodium alginate with 400% (w/w relative to alginate) honey and added red cabbage extract, crosslinked with 36 mM CaCl2	In vitro Porosity; mechanical properties (tensile strength, elongation); swelling; water retention; pH-responsive color change; antibacterial activity (S. aureus, E. coli); antioxidant activity (DPPH scavenging); biocompatibility (L929 fibroblasts proliferation)	Lotfinia et al. [148]
To develop novel double-network hydrogels composed of acylated chitosan and PVA, incorporating honey for improved wound dressing functionality	Double-network hydrogel consisting of poly(vinyl alcohol), acylated chitosan (ACS), and honey (formulations with 5%, 10%, 15% w/w honey)	In vitro Swelling capacity, mechanical strength (tensile test), thermal properties (TGA, DSC), porosity (SEM), FTIR, degradation, antibacterial activity (S. aureus, E. coli), cytocompatibility (L929 cells), pH-responsiveness	Khaleghi et al. [149]
To develop chitosan–alginate–honey hydrogel films with optimized physicochemical, mechanical, and antibacterial properties for wound dressing	Hydrogel films prepared from chitosan, sodium alginate, and 2.5–10% (w/v) natural honey, crosslinked with calcium chloride (CaCl2)	In vitro Swelling index, moisture retention, water vapor transmission rate (WVTR), mechanical strength, morphology (SEM), FTIR, thermal stability (TGA), antibacterial activity (S. aureus, E. coli)	Saberian et al. [150]
To develop and characterize quaternized chitosan/pectin hydrogel films loaded with ethanolic propolis extract for enhanced wound healing and antibacterial activity	Hydrogel films based on quaternized chitosan, pectin (2.5%), glycerol (plasticizer), crosslinked with CaCl2, with 5–15% ethanolic propolis extract	In vitro Mechanical properties (tensile strength, elongation), swelling ratio, degradation, antibacterial activity (S. aureus, E. coli), DPPH antioxidant activity, hemolysis, in vitro wound healing (scratch assay, HaCaT cells)	Phonrachom et al. [143]
To evaluate the therapeutic properties of gellan gum hydrogels incorporated with varying concentrations of Acacia stingless bee honey (SBH) for wound healing	Hydrogel films based on low-acyl gellan gum with 10%, 15%, and 20% (v/v) SBH (from Heterotrigona itama, Acacia mangium); crosslinked with CaCl2	In vitro Swelling ratio, water vapor transmission rate, disk diffusion antibacterial activity (E. coli), cell viability and proliferation (3T3-L1 fibroblasts), wound closure rate, scratch assay, FTIR, UV-vis, XRD	Mahmod et al. [151]
To evaluate whether coating polypropylene mesh with pectin-honey hydrogel (PHH) improves peritoneal regeneration and reduces adhesions in an acute hernia rat model	Polypropylene mesh coated with PHH prepared from 1:1 (v/v) aqueous honey solution and pectin added at 0.5:1 (w/v), dried and gamma-irradiated before implantation	In vivo Adhesion formation scores, peritoneal regeneration (histology), COX-2 expression (IHC), inflammation grade, mesh integration	Vercelli et al. [152]
To develop honey-based hydrogels using irradiation and freeze-thawing for wound dressing	Hydrogels composed of 10 parts PVA, 1.5–3.5 parts CM-chitosan, and 1.5–3.5 parts honey, total polymer conc. 15 wt%	In vitro and in vivo Gel content, degree of swelling, evaporation rate, mechanical strength, antibacterial activity (E. coli), wound healing efficacy in mice	Afshari et al. [153]
To develop and optimize an in situ forming thermoresponsive gel containing Acacia honey and glycyrrhizic acid for wound healing	Optimized gel composed of 20% poloxamer 407, 2% HPMC K100M, 2% Acacia honey, 0.1% glycyrrhizic acid	In vitro and in vivo Rheological properties, gelation temperature/time, drug release kinetics, antioxidant activity (DPPH), antibacterial activity (S. aureus, E. coli), cytocompatibility (L929), wound healing in rats (epithelialization, re-epithelialization score, collagen deposition)	Jha et al. [142]
To prepare honey-based hydrogels and assess their antimicrobial and burn-healing efficacy compared to a commercial product	Six hydrogel formulations with 25%, 50%, and 75% (w/w) honey prepared using either Carbopol 934 or chitosan; hydrogel base included triethanolamine (TEA), methyl paraben, and deionized wate	In vitro and in vivo (mice model) Visual assessment (homogeneity, color), pH measurement, swelling index (PBS pH 5.5), spreadability test, in vitro honey release (dialysis, UV-Vis 340 nm), antimicrobial activity (disk diffusion, S. aureus, P. aeruginosa, K. pneumoniae, S. pyogenes), daily wound contraction, histology (capillary formation, epidermal regeneration, acanthosis), bacterial swabs and culture	El-Kased et al. [49]
To investigate the effect of honey-enriched chitosan/hyaluronic acid hydrogels on wound healing performance	Chitosan–HA hydrogels with honey: CH1–CH4 (1–6% HA, 0–3% honey), CHB1–CHB4 with balanced honey to chitosan/HA ratios	In vitro and in vivo Physicochemical (swelling, morphology SEM), in vivo wound closure (histology: H&E staining), biocompatibility	Salva et al. [154]
To develop physically cross-linked chitosan/PVA hydrogels incorporating honey and allantoin via freeze–thaw cycles, and assess their wound healing potential	Hydrogels made from chitosan:PVA (30:70 v/v) with honey (diluted 1:1 w/w) and allantoin (4%), combined via freeze–thaw (3 cycles)	In vitro and in vivo Physicochemical: swelling (324–476%), gel content (<10%), mass loss, crystallinity (FTIR, XRD, DSC)	Koosha et al. [137]
To develop and evaluate a new pectin-honey hydrogel dressing with antibacterial and biocompatible properties	Hydrogel composed of pectin and Manuka honey (1:1 v/v), dried into films and sterilized by gamma irradiation	In vitro and in vivoSwelling, WVTR, hydrogen peroxide and MGO content, antibacterial activity (S. aureus, E. coli), cytotoxicity (L929 fibroblasts via MTT) subcutaneous and intraperitoneal implantation, histological evaluation, IL-1β, IL-6, TNF-α, and PGE2 levels	Giusto et al. [138]
To develop dual cross-linked alginate hydrogels incorporating honey and assess their structural, antimicrobial, and healing efficacy	Sodium alginate hydrogel crosslinked ionically (Ca2+) and covalently (EDC/NHS), with honey concentrations of 2%, 4%, 6%, 8%, and 10%	In vitro and in vivo FTIR, XRD, nanoindentation, swelling behavior, degradation time, SEM, cytocompatibility (HaCaT, 3T3), antibacterial activity (MRSA, E. coli), in vivo wound contraction (4% HSAG: 94.56% after 14 days), histology, OCT imaging	Mukhopadhyaya et al. [141]
To develop and evaluate a hydrogel sponge composite containing curcumin and honey for enhanced wound healing	Hydrogel sponge composed of chitosan (1–3% w/v), sodium alginate (1–3% w/v), 1% w/v curcumin in ethanol, 10 mL honey (per batch), crosslinked with acrylamide; prepared via solvent casting and in situ polymerization	In vitro and in vivo (excision wound model in rats); In vitro and in vivo Swelling capacity, moisture retention, tensile strength, WVTR, SEM, in vitro release, bioadhesion, hemocompatibility, biodegradability, stability, wound closure rate, histological evaluation	Momin et al. [155]

) illustrate the versatility of honey-based hydrogels. Hydrogel-based systems containing honey are most often discussed through their rheological behavior, since viscoelasticity governs spreadability, retention in cratered ulcers, and patient comfort. Typical reports include storage and loss moduli, swelling ratios, and degradation kinetics of the polymer network. These measurements are often accompanied by data on water vapor transmission and absorbency, which together illustrate the capacity of hydrogels to maintain a moist but non-macerating environment. In addition, several studies examine the preservation of enzymatic activity and methylglyoxal content following sterilization or storage, highlighting the importance of biological stability in such formulations.

4. Limitations

Despite the considerable therapeutic promise of honey-based systems in wound management, several limitations must be addressed to enable successful clinical translation and commercial application. A primary challenge is the inherent variability of natural honey, which depends on multiple factors, including floral source, geographic origin, harvesting season, and storage conditions. This variability leads to inconsistent bioactivity, affecting antimicrobial potency, antioxidant levels, and wound healing efficacy. As a result, achieving standardization across batches remains a key barrier to reproducibility in both laboratory research and large-scale manufacturing.

In this regard, monofloral honeys, especially Manuka honey (Leptospermum scoparium), offer a significant advantage. Manuka honey exhibits a more consistent chemical profile, particularly with regard to its high methylglyoxal (MGO) content, which is strongly linked to antibacterial activity. It also benefits from established grading systems such as the Unique Manuka Factor (UMF^®), allowing for reliable quantification of bioactivity and compositional authenticity. These features make Manuka honey easier to standardize, and therefore more compatible with the stringent requirements of regulatory bodies. However, this does not exclude the potential use of other types of honey, many of which also possess valuable therapeutic properties; however, their broader application requires rigorous quality control and compositional standardization to ensure consistency and reproducibility in medical formulations.

Nevertheless, most honey-based nanomaterials and advanced delivery systems currently lack formal regulatory classification. Products combining honey with metals (such as silver or zinc) or drugs require full toxicological profiles, stability assessments. Nanoparticles, especially those based on metals and metal oxides, are widely used in wound care due to their strong and broad-spectrum antimicrobial activity. However, their clinical translation is hindered by several concerns. One of the primary challenges is potential cytotoxicity at higher concentrations [156]. Regulatory approval is further complicated by these variations, as consistent safety profiles are required for clinical validation [157].

Electrospun nanofibers offer a highly tunable and ECM-mimicking platform for wound healing applications, yet they also come with specific technical constraints. The electrospinning process often relies on organic solvents that may be incompatible with natural bioactive substances like honey, enzymes, or peptides. The resulting nanofibrous mats, while highly porous, often suffer from weak mechanical strength and poor flexibility unless reinforced with synthetic polymers. Chemical crosslinkers such as glutaraldehyde are frequently employed to enhance their structural integrity; however, their use must be carefully optimized due to potential cytotoxicity and residual reactivity [158]. Without integration into composite systems, nanofiber mats may also lack sufficient adhesiveness or moisture retention capacity for effective wound coverage [159].

Hydrogels are widely used in wound management due to their excellent moisture retention, softness, and biocompatibility; however, they also exhibit some functional limitations. One of the main drawbacks is their inherently poor mechanical strength, resulting from their high water content, which can reach up to 90%. This compromises their structural integrity and makes them susceptible to tearing or deformation under mechanical stress. As a result, they often require reinforcement with secondary dressings or incorporation of synthetic polymers to improve durability, elasticity, and load-bearing capacity, especially when applied to mobile or high-tension anatomical regions [160].

Importantly, regardless of the delivery platform, proper sterilization of honey-based wound dressings remains a critical requirement for clinical application. To advance honey-based wound technologies toward clinical use, future research must focus on the standardization of honey composition, development of scalable fabrication methods, and generation of robust preclinical and clinical data.

5. Conclusions and Future Perspective

Honey-based wound dressings are becoming an interesting alternative for traditional therapies, especially in the treatment of chronic wounds and infected lesions. Their natural antimicrobial, anti-inflammatory, and regenerative activities are well documented, and the use of modern delivery platforms like hydrogels, nanofibers or nanoparticles allows for improving their stability and controlled release profile. These systems can also help in keeping honey longer on the wound surface and improving patient comfort during the healing process. However, some limitations remain. Many honey-based materials have poor mechanical strength, and their structure may not be stable enough in dynamic wound environments.

Additionally, the natural variability of honey composition makes it difficult to standardize products and complicates regulatory approval. Proper sterilization methods also need to be optimized, because some common techniques can destroy active components in honey. In the future, development will probably go toward smart and multifunctional dressings. These may include biosensors that react to wound conditions like pH, temperature or bacterial infection, enabling real-time feedback. Moreover, advanced fabrication methods such as 3D and 4D bioprinting give the opportunity to create dressings that are customized to wound shape and respond to external stimuli. Combining these technologies with honey-based formulations may bring more efficient and personalized wound care solutions, but further clinical validation and scalable production strategies are still needed.