Clinical and Postoperative Applications of Manuka Honey in Wound Healing: An Evidence‐Based Review

ABSTRACT

Chronic and postoperative wounds remain challenging to manage, with high risks of infection, delayed healing and increased costs. Manuka honey offers antibacterial, anti‐inflammatory, antioxidant and tissue‐regenerative properties through methylglyoxal, phenolic compounds, high sugar content and low pH. The main objective is to review the mechanisms, clinical outcomes and applications of Manuka honey in wound care. A narrative review of PubMed, Scopus and Google Scholar identified studies on surgical site management, graft or flap bed preparation, chronic wounds and novel delivery systems, prioritising randomised controlled trials and high‐quality observational data. Results have shown that Manuka honey demonstrates broad‐spectrum antimicrobial and antibiofilm effects, supports non‐traumatic debridement and modulates inflammation to promote granulation and re‐epithelialisation. Clinical studies show reduced bacterial load, faster healing and improved comfort in surgical and chronic wounds. Operative uses include pre‐grafting bed conditioning, adjunctive treatment for infected wounds and integration with negative pressure wound therapy. Emerging delivery approaches, such as bioengineered honey–collagen dressings and nanofibrous scaffolds, show promise for enhancing postoperative outcomes. To conclude, Manuka honey is a versatile and promising adjunct in modern wound care management. Standardised application protocols and robust, high‐quality surgical trials are urgently needed to confirm its effective role in perioperative clinical practice.

Key Points

• Medical grade Manuka honey demonstrates antibacterial, antibiofilm, anti‐inflammatory, and tissue‐regenerative properties in wound healing.

• Clinical studies show improved healing outcomes in diabetic foot ulcers, venous leg ulcers, pressure injuries, and postoperative wounds.

• Medical grade Manuka honey may enhance surgical wound care through integration with advanced therapies such as hydrogels, nanofibers, and negative pressure wound therapy.

• Further high‐quality randomized clinical trials and standardized protocols are needed for broader clinical adoption.

Abbreviations

∑FBEC

fractional biofilm eradication concentration

ADM

acellular dermal matrix

ASCs

adipose‐derived stem cells

BCMH

bioengineered collagen Manuka honey

CD

Conventional dressings

CFU/mL

Colony‐Forming Units per millilitre

DFU

diabetic foot ulcers

DHA

Docosahexaenoic acid

E. coli

Escherichia coli

E. faecalis

Enterococcus faecalis

EPA

eicosapentaenoic acid

EPM

extracellular polymeric matrix

IL‐10

interleukin‐10

IL‐12

interleukin‐12

IL‐1b

interleukin‐1 beta

IL‐1ra

interleukin‐1 receptor antagonist

IL‐4

interleukin‐4

IL‐6

interleukin‐6

kGy

kilograys

LMICs

low‐ and middle‐income countries

MBC

minimum bactericidal concentration

MFC

minimum fungicidal concentration

MGO

methylglyoxal

MH

Manuka honey

MHID

Manuka honey‐impregnated dressings

MHM

Manuka honey microneedles

MIC

minimum inhibitory concentration

MMP‐9

matrix metalloproteinase‐9

MRSA

methicillin‐resistant Staphylococcus aureus

nAg

nanocrystalline silver

OTC

over the counter

P. aeruginosa

Pseudomonas aeruginosa

pH

potential of hydrogen

RCT

randomised controlled trial

Rx

prescription

S. aureus

Staphylococcus aureus

SOC

standard of care

TLR4

Toll‐like receptor 4

TNF

tumour necrosis factor

TNFa

tumour necrosis factor alpha

UMF

unique Manuka factor

VAC

vacuum‐assisted closure therapy

VEGF

vascular endothelial growth factor

VLU

venous leg ulcers

1. Introduction

Chronic wounds, including diabetic foot ulcers and venous leg ulcers, represent a growing challenge for healthcare worldwide, impacting the quality of life of nearly 2.5% of the total population in the United States, with a larger fraction being the elderly [1]. Notably, some chronic wounds have a 5‐year mortality that exceeds some cancers and are associated with > 15% of all skin disease‐related deaths [2]. The socioeconomic burden is further escalated due to the clinical complications of chronic wounds, such as limb amputations or life‐threatening infections [3]. Hence, the urgent need for management and equitable access to care is underscored [4]. Simultaneously, surgical wounds represent an overlooked burden, especially when complicated by surgical site infections (SSI), as up to 5%–10% of surgical procedures result in SSIs and could cause longer hospital stays, higher morbidity and even death [5]. Furthermore, particularly in individuals with diabetes, advanced age or vascular diseases, surgical wounds that do not heal normally may develop into chronic non‐healing wounds [6]. However, conventional treatments such as debridement and frequent dressing changes do not consistently achieve high healing rates across patient populations and wound types. Randomised controlled trials in venous leg ulcers reported that patients receiving conventional therapy had an average wound area reduction of just 8.4% at 24 weeks, compared to 59.6% with advanced treatment [7]. A similar trial in diabetic foot ulcers demonstrated significantly greater wound healing and a larger reduction in wound area using a human acellular dermal matrix (ADM) compared to conventional care [8]. Furthermore, the rise of antibiotic resistance, especially among pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa , further hinders the effectiveness of traditional treatment and necessitates the search for alternative therapies. Alternative approaches, such as the medical application of Manuka honey, have been shown not only to possess potent, broad‐spectrum antibacterial activity but also to exhibit anti‐biofilm activity. The potential use of combination therapy along with antibiotics was thus warranted. An in vitro study concluded that the Medihoney‐rifampicin combination was more effective than other antibiotic combinations against established staphylococcal biofilms [9].

Containing active components such as hydrogen peroxide and Methylglyoxal (MGO), Manuka honey has also been shown to promote rapid wound closure when applied topically [10]. As wound infections become increasingly common, medical‐grade honey, including Manuka honey, has been adopted to help reverse and treat such wounds. Being safe and effective in treating various types of wounds, Manuka honey is a potent treatment for extravasation injuries in preterm neonates, with improvements in wound healing observed in 7–67 days, without infections or loss of motion [11]. Undoubtedly, the clinical integration of honey‐based products has yielded positive outcomes, including reduced hospital stay times, improved pain control and decreased infection rates, which collectively contribute to indirect cost and resource savings for healthcare facilities [12].

Manuka honey is incorporated into a range of advanced wound care formulations. Additionally, emerging research is exploring the integration of Manuka honey with advanced therapies, including in cellulose acetate nanofibrous mats used as a potential wound dressing after successful fabrication via electrospinning [13]. This review aims to focus on the clinical and translational evidence supporting the use of medical‐grade Manuka honey in chronic and postoperative wound healing. Human clinical outcomes are prioritised, while in vitro and animal studies are included only to support and explain observed clinical effects. The distinguishing elements of this review are evident in its coverage of emerging synergistic therapies, innovative delivery systems and the addressing of unmet clinical needs, all supported by recent studies. Accordingly, this review emphasises evidence from human studies of chronic and postoperative wounds, with preclinical data used selectively for mechanistic context.

2. Search Strategy

A structured literature search was conducted in line with a narrative review methodology using PubMed/MEDLINE, Scopus and Google Scholar to identify studies evaluating medical‐grade Manuka honey in wound care. Search terms included combinations of ‘Manuka honey’, ‘medical‐grade honey’, ‘Leptospermum’, ‘Medihoney’, ‘methylglyoxal/MGO’, ‘UMF’, together with wound‐related terms such as ‘wound healing’, ‘chronic wound’, ‘diabetic foot ulcer’, ‘venous leg ulcer’, ‘pressure injury’, ‘burn’, ‘postoperative wound’, ‘surgical wound’, ‘surgical site infection’ and ‘negative pressure wound therapy’. Reference lists of key articles were also screened.

The search covered literature published between 1980 and 2025, with priority given to studies from the last 5 years. After duplicate removal, titles and abstracts were screened. Non‐English publications, conference abstracts, editorials and case reports were excluded. Animal‐only studies were excluded unless they provided mechanistic insights directly relevant to human wound healing.

Eligible studies included randomised controlled trials, observational studies, mechanistic investigations and high‐quality reviews, with emphasis on human clinical outcomes in chronic and postoperative wounds. Preclinical studies were included selectively to support discussion of antimicrobial, antibiofilm, immunomodulatory, debridement and tissue‐regenerative mechanisms.

3. Mechanism of Action

Manuka honey emerges as a biologically active agent in wound management due to its antimicrobial activity, ability to modulate inflammation and promote tissue regeneration. Historically, honey has been used medically; however, the breakdown of its functional ingredients and mechanisms has only recently been understood. What makes Manuka Honey unique from other types of medicinal honey is the discovery of MGO as the antimicrobial bioactive agent in 2008 [14]. The combination of MGO with phenolic compounds, including phenolic acid and flavonoids, high sugar components and low pH, provides a synergistic effect for wound healing [15]. Figure 1 summarises the major bioactive compounds derived from Manuka honey.

FIGURE 1.

Key bioactive components of Manuka honey and their plant/nectar origins. Created with biorender.com.

3.1. Antimicrobial Effect

An essential property of Manuka Honey is its antimicrobial effects. While microorganisms are known to develop resistance to conventional antibiotics, no evidence of resistance against honey active ingredients has been reported, which serves as an essential alternative for antimicrobials and supports antibiotic stewardship [16]. Antimicrobial activity refers to the ability of an agent or substance to induce cell death (microbiocidal) or inhibit the replication and enzymatic activity (microbiostatic) of microorganisms, including parasites, fungi, bacteria and viruses. This is measured using minimum inhibitory concentration (MIC) for microbiostatic effect and minimum bactericidal or fungicidal concentration (MBC or MFC) for microbiocidal effect [17].

The antimicrobial properties of Manuka Honey arise from two main mechanisms: oxygen‐free radicals and MGO. Oxidised sugars generate hydrogen peroxide, a free radical that damages microbial DNA and inhibits replication. However, it is neutralised by the catalase enzyme present naturally in blood and tissue [18]. On the other hand, methylglyoxal, a derivative of dihydroxyacetone (DHA), is a non‐peroxide antibacterial compound that remains active in the presence of catalase. It has been proven to show solely bactericidal effects when other antimicrobial bioactive agents in Manuka honey are neutralised [19].

3.1.1. Methylglyoxal

MGO is the primary antimicrobial compound responsible for the UMF grading system used to assess the strength of Manuka honey. The New Zealand Honey Association established the Unique Manuka Factor (UMF) grading system to classify it based on purity, authenticity and antimicrobial strength. It is based on the presence of MGO, DHA and leptosperin [20]. Several studies have reported the MICs against Gram‐positive and Gram‐negative organisms, including both multi‐drug‐resistant and drug‐susceptible strains. It was concluded that lower (5+ and 10+) UMF honey exhibited greater antibacterial activity compared to higher (15+) UMF honey. This has been attributed to the UMF being labelled at different points in the product's shelf life. This affected the DHA: MGO ratio; hence the inaccurate representation by the UMF grading system [21, 22].

3.1.2. Defensin 1

Other mechanisms, including Bee Defensin‐1, a peptide secreted by bees, work independently from MGO by forming pores in the bacterial cellular membrane, accelerating cell death. Additionally, it aids wound repair by increasing matrix metalloproteinase‐9, promoting keratinocyte proliferation and facilitating re‐epithelialisation [23]. Some studies have shown a sharp reduction in antimicrobial effect when Defensin‐1 is deactivated by heat or proteases [19]. In contrast, another study showed that Manuka honey had the lowest levels of defensin 1, with no antimicrobial effect [24].

3.1.3. Low pH and High Osmolarity

Low pH and high osmolarity synergistically enhance the MGO antimicrobial effect, but are not sufficient alone. Low pH inactivates the bacterial enzymes and dysregulates cellular function and viability. The high osmolarity causes cellular dehydration by moving intracellular fluid through osmosis [25].

3.1.4. Broader Antimicrobial Spectrum: Bacteria, Fungi and Viruses

Manuka honey is effective against resistant bacteria, various fungal species and viruses. Manuka honey offers antimicrobial properties, including activity against antibiotic‐resistant bacteria such as MRSA and P. aeruginosa. The mechanism involves disrupting bacterial membranes and inhibiting bacterial growth. P. aeruginosa biofilm formation, which is primarily attributed to its sugar contents [26]. Regarding MRSA surgical site infections, Manuka honey microneedles (MHM) synthesised at concentrations greater than 10% and those prepared by vacuum have been shown to be the most bactericidal [27].

In addition to antibacterial properties, recent studies are exploring its antifungal and antiviral efficacy. A recent study showed significant efficacy against three clinically relevant 𝘚𝘱𝘰𝘳𝘰𝘵𝘩𝘳𝘪𝘹 species using a fungistatic mechanism. However, treatment with catalase eliminated its activity [28]. Moreover, combined Manuka Honey with conventional antifungals (fluconazole, itraconazole, clotrimazole, miconazole) had an additive effect and reduced the MIC value in Malassezia species [29].

The virucidal activity of MH has been proven against the influenza virus, the Respiratory syncytial virus, the Varicella‐Zoster Virus and the Rubella Virus [30, 31, 32]. Studies have shown selective antivirulence activity, with toxicity to host cells remaining low. This activity may be attributed to the MGO substance and the inhibition of essential viral proteins, which in turn decrease entry, replication and release. It also showed a 1000‐fold enhancement when combined with antiviral neuraminidase inhibitors, such as oseltamivir [33].

3.1.5. Antibiofilm Effect

Biofilm is a layer of Extracellular Polymeric Matrix (EPM) formed by a group of microorganisms isolating itself from chemical degradation and the host immune system. Antibiofilm aims to stop the formation of further biofilms, disrupts EPM, reduces adhesion to the surface and helps the penetration of antimicrobial agents. In vivo studies have demonstrated the efficacy of MH in reducing biofilms of microorganisms, such as Staphylococcus aureus , Streptococcus agalactiae and Pseudomonas aeruginosa , with no efficacy against Enterococcus faecalis and reported regrowth after 24 h of treatment [34, 35]. Moreover, when comparing the Fractional Biofilm Eradication Concentration (∑FBEC) of vancomycin against S. aureus and gentamicin against P. aeruginosa with and without adding MH, it proved an in vitro synergistic and additive interaction, respectively, when MH was added with other antibiotics [36]. A study exploring the pre‐ and post‐treatment of Enterococcus coli O157:H7 with Manuka Honey resulted in reduced biofilm production and integrity, metabolic activity and overall cell count by 90% [37].

3.1.5.1. Tissue Debridement and Protection

During wound healing, necrotic tissue, debris and contaminated tissue are removed from the wound bed to promote healing. An additional protective layer is crucial to prevent further trauma and infection. The viscous properties of honey, combined with its nutrient‐rich composition, create a gel‐like barrier that protects the wound from further contamination while allowing it to remain hydrated and moist. Meanwhile, it serves as a sugar‐rich source for endothelial cells and fibroblasts, allowing them to proliferate and synthesise the extracellular matrix [38]. The majority of Manuka Honey is composed of sugars that function as an osmotic gradient, which mechanically mobilises wound exudate, along with bacteria, debris and necrotic tissue, to the surface. Additionally, the enzymes present in MH enhance the activity of endogenous autolytic enzymes, allowing for the more effective clearance of necrotic tissue [39]. This collectively allows a non‐traumatic debridement of the wound.

In a porcine wound model, Manuka honey was demonstrated to increase collagen density and lower macrophage activity. While it exhibited epidermal regeneration and quicker re‐epithelialisation, further clinical trials are required to evaluate further the arrangement of collagen fibres, the structural integrity of the dermal tissue. This is essential to determine whether these findings are translatable to human wound healing [40].

3.1.5.2. Immunomodulation

The immune response to wound healing is divided into four phases: (a) haemostasis responsible for the fibrin clot, (b) inflammatory phase in which neutrophils control microbial contamination and macrophages release proinflammatory cytokines: Tumour necrosis factor (TNF), Interleukin (IL‐1b, IL‐6) followed by an anti‐inflammatory response by releasing IL‐10 and growth mediators, (c) proliferative phase including granulation tissue and angiogenesis, (d) remodelling phase where immune cell density declines and tissue is strengthened [41].

A balanced regulation of proinflammatory and anti‐inflammatory pathways by Manuka Honey enables the wound to exhibit an inflammatory response that promotes healing without overwhelming it. Maunka honey primarily signals a pro‐inflammatory response. In vitro studies demonstrated a significant increase in macrophage activation, neutrophil recruitment, chemokine synthesis, and increased gene expression of IL‐1β, IL‐6 and TNF‐α, accompanied by increased protein synthesis of the latter. In vivo studies showed an activation of inflammatory response independent of the Toll‐like receptor (TLR4) signalling pathway [42] Effects of different concentrations of 0.3% and 5% of Manuka honey was shown to have various outcomes on modulating chemokines, cytokines and growth factors; where lower concentrations decreased IL‐12, IL‐1ra, IL‐4, TNF‐α, and higher concentrations increased TNF‐α. Once again, future investigations are warranted to integrate these results into physiologically representative conditions [39].

Collectively, these immunomodulatory properties contribute to the therapeutic potential of Manuka honey in managing wounds with impaired or dysregulated inflammatory responses. The therapeutic effects of Manuka honey can be further visualised in Table 1, which maps its molecular actions to specific phases of wound healing. The diverse mechanisms by which Manuka honey facilitates wound healing are also illustrated in Figure 2.

TABLE 1.

Summary of Manuka honey's key mechanisms mapped to wound healing phases.

Healing phase	Key effect	Specific mechanism	References
Inflammation	↓ IL‐6, TNF‐α, ↑ IL‐10, keep the wound acidic (pH 3.2–4.5)	Immunomodulation of macrophages/neutrophils; low pH limits protease activity	[43, 44, 45]
Debridement	Promotes gentle autolytic debridement	Strong osmotic gradient draws lymph/exudate while maintaining a moist bed	[46]
Proliferation	↑ Granulation tissue formation	Rise in fibroblast proliferation vs. untreated controls; VEGF up‐regulation.	[37, 47, 48]
Epithelialisation	Speeds re‐epithelialisation, faster scratch‐wound closure	Keratinocyte migration driven by MMP‐9 and Ca2+‐signalling pathways	[49, 50, 51]
Antimicrobial	Disrupts biofilms and inhibits pathogens	MGO cross‐links proteins; H₂O₂ generation; synergy with β‐lactams vs. MRSA and with rifampicin vs. P. aeruginosa	[52, 53]

FIGURE 2.

Mechanisms of Manuka honey with wound healing. Created with biorender.com.

4. Clinical Evidence by Wound Type

Multiple randomised controlled trials have evaluated medical‐grade Manuka honey dressings or honey‐based wound formulations across diverse wound types (Table 2). In the treatment of diabetic foot ulcers (DFUs), Manuka honey dressings seem to aid in tissue repair and adjust the wound environment to facilitate healing. One Randomised Controlled Trial (RCT) indicated that dressings infused with Manuka honey promoted granulation and decreased wound size more effectively than traditional methods in patients with neuropathic diabetic foot ulcers, implying that its antimicrobial and anti‐inflammatory properties are crucial for progressing chronic wounds toward healing [58]. In another study comparing Manuka honey with nanocrystalline silver and standard gauze, no notable difference in healing rates was observed; however, it reported enhanced pain management and better tolerability of dressings with honey, emphasising its positive patient‐centred outcomes [56]. In support of these results, a pilot RCT conducted in Saudi Arabia demonstrated that, when compared to standard DFU care alone, the use of Manuka honey resulted in fewer minor amputations, quicker infection eradication, lower hospitalisation rates and higher complete healing rates at 6 weeks [59].

TABLE 2.

Summary of randomised controlled trials (RCTs) evaluating Manuka honey in wound healing across various indications.

RCT design	Sample size	Country and year	Wound type	Comparator	Primary outcome(s)	References
Multicentre, open‐label, parallel‐group RCT	n = 99 children—aged between 2 months and 17 years old	India, 2021	Pressure injuries in children	Standard care	Median healing time: 7 days (95% CI: 6–7) vs. 9 days (7–10) for intervention vs. control; p = 0.002 (log‐rank).	[54]
Single centre prospective randomised trial	n = 40, M = 22, F = 18	India, 2020	Post‐op mastoid cavity	Antibiotic‐soaked gel	The infection rate in the MH group decreased from 75% pre‐operatively to 35% at 3 months; 65% had sterile cultures. MH showed activity against Pseudomonas, Proteus, Klebsiella, E. coli and S. aureus ; eradicated all anaerobic infections. No significant difference was observed between the test and control groups in terms of sterility (p = 0.28) or Merchant score (p = 0.09).	[55]
Open‐label prospective pilot, three parallel RCT (n = 31)	n = 31, M = 18, F = 13	Hong Kong, 2017	Diabetic foot ulcers (DFUs)	Nanocrystalline silver, conventional dressings	Cumulative ulcer healing incidence after 12 weeks: Proportion healed: nAg 81.8%, MH 50%, conventional 40%. Ulcer size reduction rate: The nAg group had the highest reduction rate (97.45%), compared to the MH (86.24%) and conventional (76.91%) groups.	[56]
Prospective, randomised, single‐blinded RCT	n = 55, M = 17, F = 29	UK, 2017	Post‐op eyelid wounds	Standard dressing (Vaseline)	Trend toward better outcomes with Manuka: less skin distortion (1.6 vs. 1.8, p = 0.07), less palpable scar (1.8 vs. 2.0, p = 0.08), less stiffness (1.3 vs. 1.6, p = 0.058). No difference in grading at 1 or 4 months, but scar pain was significantly lower at 4 months (0.48 vs. 1.9, p = 0.005).	[57]
Prospective randomised, controlled, double‐blinded RCT	n = 63	Greece, 2014	Neuropathic diabetic foot ulcers (DFUs)	Conventional dressings	MHID vs. CD: faster healing (31 ± 4 vs. 43 ± 3 days, p < 0.05); higher sterilisation at week 1 (78.1% vs. 35.5%), but % ulcers healed similarly (97% vs. 90%).	[58]
Prospective double‐blind, randomised clinical trial	n = 57, M = 31, F = 26	Saudi Arabia, 2013	Diabetic foot ulcers (DFUs)	Conventional treatment	The honey group showed faster infection clearance and shorter hospital stays (p < 0.05); higher complete healing rates at 6 weeks and 6 months (p < 0.05); fewer toe amputations (9.7% vs. 34.6%, p < 0.05); and no major amputations or deaths in either group.	[59]
Prospective open‐label multicentre RCT (n = 108)	n = 108, M = 35, F = 73	Ireland, 2008	Sloughy venous leg ulcers (VLUs)	Hydrogel	MRSA eradicated in 70% of MH‐treated wounds vs. 16% with hydrogel after 4 weeks. P. aeruginosa cleared in 33% (MH) vs. 50% (hydrogel).	[60]
Open‐label, multicentre RCT	n = 368	New Zealand, 2008	Venous Leg Ulcers (VLUs)	Usual care (alginate, hydrofibre, hydrocolloid, foam, hydrogel, non‐adherent, iodine or silver dressings)	Proportion of participants with a completely healed reference ulcer at 12 weeks: 55.6% (honey) vs. 49.7% (usual care); absolute increase 5.9% (95% CI −4.3 to 15.7), p = 0.258; no significant difference after adjustments.	[61]
Single‐centre RCT (n = 100)	n = 100	UK, 2006	Post‐op Toenail Surgery Wounds	Paraffin tulle gras	Mean time healing: honey 40.3d vs. paraffin 39.98d. Partial avulsions healed faster with paraffin (19.62d vs. 31.76d, p = 0.01), but no significant difference. difference for total avulsions (45.28d vs. 52.03d, p = 0.21).	[62]

In chronic venous leg ulcers (VLUs), which frequently face issues with bacterial colonisation and slow healing, medical‐grade Manuka honey has also shown positive effects. Gethin and Cowman reported significant reductions in bacterial levels in sloughy VLUs treated with honey compared to those treated with hydrogel, highlighting its antimicrobial effectiveness in vivo [60]. Although an extensive multicentre study did not find a statistically significant difference in healing rates, patients using honey‐impregnated dressings reported higher satisfaction. They required fewer dressing changes, suggesting that it may serve as a beneficial adjunct in long‐term care settings [61].

The therapeutic potential of Manuka honey dressings has also been explored in the treatment of pressure injuries and postoperative wounds, further reinforcing its versatility. In critically ill paediatric patients with hospital‐acquired pressure injuries, honey‐based dressings led to significantly faster wound closure without an increase in adverse events, affirming both their efficacy and safety in vulnerable populations [54]. Likewise, in the context of eyelid surgery, the postoperative application of Manuka honey has been shown to improve wound healing quality and minimise scarring compared to standard care [57]. However, another RCT reported that following toenail surgery, using honey dressings showed no statistical difference compared to using paraffin tulle gras [62].

Beyond its role in tissue regeneration, Manuka honey's antimicrobial activity may contribute to its wound‐healing efficacy. While this property has been widely characterised in vitro, clinical studies have also demonstrated significant reductions in bacterial load. For example, honey‐treated VLUs demonstrated microbiological improvement [60]. In addition, according to Damodharan et al., topical Manuka honey resulted in persistent bacterial clearance in a randomised experiment comprising post‐mastoidectomy cavities; by 3 months, 65% of ears treated with honey were culture‐negative, compared to 80% with antibiotic‐soaked foam. These results support the dual antibacterial and wound‐healing properties of Manuka honey, as well as its exceptional tolerability for a variety of patient populations [55]. Overall, the strongest clinical evidence supports Manuka honey use in diabetic foot ulcers, venous leg ulcers, pressure injuries and selected postoperative wounds.

5. Manuka Honey Products and Evidence Base

Several Manuka honey‐based formulations are already Food and Drug Administration (FDA) ~cleared for wound management. This distinction is clinically important, as evidence for wound management should be interpreted in the context of regulated, sterilised wound‐care formulations rather than consumer‐grade honey products. Table 3 summarises the key products, their indications and the corresponding evidence levels.

TABLE 3.

FDA‐cleared Manuka honey wound dressings: formulations, indications and supporting levels of evidence.

Product and manufacturer	Cleared formulation(s)	Clinical indications (FDA IFU)	Level of evidence	References
Medihoney—Integra	Calcium‐alginate pads/ropes; hydrocolloid sheet/paste; 100% honey gel	DFU, VLU, pressure ulcers (I‐IV), burns, surgical/traumatic wounds	Level 1b—two RCTs	[61, 63, 64]
TheraHoney—Medline	100% honey gel; honey gauze/sheet; foam dressings	Partial/full‐thickness wounds, leg/pressure ulcers, DFU, burns	Level 4—case series; phase‐4 trial ongoing	[65, 66]
MANUKAhd—ManukaMed	Honey gelling‐fibre pad/rope	Leg/pressure ulcers, DFU, burns, surgical/traumatic wounds	Level 4—prospective case series	[67]
MANUKAtex—ManukaMed	Honey‐impregnated viscose gauze	OTC: minor wounds; Rx: ulcers, DFU, burns	Level 4—manufacturer case reports	[68]
Wound Dressing with Manuka Honey—Manuka Health NZ	Sterile honey sheet (OTC & Rx)	OTC: minor wounds; Rx: ulcers, DFU, pressure ulcers, donor sites	Level 1a—included in systematic reviews	[69, 70]

6. Limitations and Challenges

Despite growing evidence for the benefits of Manuka honey in wound care, several limitations hinder its widespread clinical adoption. One central review identified in our study is the heterogeneity of studies conducted on Manuka honey. The randomised controlled trials analysed differ in sample sizes, wound types, honey concentrations, treatment durations and outcome measures, making comparison and synthesis challenging. Moreover, while clinical trials investigating Manuka‐based hydrogels have shown promising results, their clinical translation remains limited due to the absence of universally accepted guidelines on dosing, formulation and application frequency. Another key challenge is the limited number of high‐quality RCTs evaluating Manuka honey's effectiveness for specific wound types. Many existing studies have low sample sizes, lack long‐term follow‐up, or were conducted more than a decade ago.

Additionally, there is a notable lack of studies involving high‐risk populations such as geriatric and immunocompromised patients, who are particularly susceptible to chronic wounds and delayed healing. Yet, they remain underrepresented in clinical trials, thereby limiting generalizability [71, 72]. Lastly, although Manuka honey is a natural product, the cost of processing it to medical‐grade standards poses a significant barrier, particularly in low‐income countries. Furthermore, clinicians in such settings may lack adequate training or familiarity with its use, highlighting the need for educational programmes, clinical guidelines and regulatory frameworks to support its integration into mainstream wound care.

7. Regulatory and Quality Considerations

A critical distinction must be made between commercial Manuka honey sold for consumer use and medical grade Manuka honey, as commercial Manuka honey faces many concerns such as important regularity, quality and safety challenges that limit its consistent clinical use. Also, a significant obstacle of commercial Manuka honey is the lack of a globally standardised regulatory framework to monitor its quality, processing and labelling. This regulatory gap has led to problems such as mislabelling, fraud and adulteration, which in turn may decrease clinician trust in its therapeutic use [73]. One example of a successful regional initiative addressing this issue is the UMF grading system, which was previously discussed. However, in contrast, medical grade Manuka honey is produced under controlled manufacturing conditions, where factors such as sterilisation, formulation, packaging and regulatory approval are highly maintained for the intended use of therapeutic wound care management.

Another primary safety concern of commercial Manuka honey is the potential microbial contamination of unsterilised Manuka honey, which may contain spores from Bacillus and Clostridium species. However, research has shown that gamma irradiation, up to 25 kilograys (kGy), effectively sterilises honey without compromising its antimicrobial activity [74, 75]. This method is now widely used in the production of medical‐grade honey. Other techniques, such as heat sterilisation, are more commonly applied but may damage important antibacterial compounds. Therefore, irradiation and ozonation are considered superior for preserving the therapeutic properties of Manuka honey while ensuring microbial safety [76].

In addition to microbial safety, it is also essential to consider the clinical tolerability of both commercial and medical grade Manuka honey, particularly about allergy risk and diabetic wound care applications. These patient‐centred safety aspects have been explored in recent clinical studies. Manuka honey is generally considered safe for topical use, including in wound care, with minimal risk of allergic reaction [77, 78]. Overall, safety concerns related to the clinical use of Manuka honey in wound management remain minimal and manageable when appropriate standards are followed.

8. Emerging Concepts: Advanced Therapy Integration

Building on the previously discussed therapeutic mechanisms of Manuka honey, this section examines its potential to improve clinical outcomes by integrating it with other wound management modalities. One promising avenue is its conceptual combination with vacuum‐assisted closure (VAC) therapy, which utilises negative pressure to reduce oedema, decrease bacterial load and improve perfusion [79, 80]. Manuka honey may act synergistically with VAC, as the vacuum system helps absorb wound exudate and exposes the wound bed, allowing the honey to exert its direct antimicrobial and anti‐inflammatory effects [44]. Furthermore, Manuka honey's high osmolarity draws fluid out of the wound bed, creating an outflow of lymph that complements VAC's mechanism by enhancing fluid removal and improving the healing environment [44]. A recent study combining VAC therapy with Manuka honey and other additional therapeutics in acute wound care reported faster median healing times of 19 days and reduced healthcare utilisation, suggesting significant potential for improved outcomes with integrated therapies [81]. However, the clinical evidence remains limited, and there are currently no standardised protocols or large‐scale trials assessing this combination. Further research is needed, particularly randomised controlled trials, to evaluate the clinical efficacy and develop honey‐based dressings that are compatible with VAC systems. Supporting this concept, a case report involving a 55‐year‐old woman with extensive necrotic abdominal lesions demonstrated complete wound healing and successful skin autografting following treatment with Manuka honey dressings and the GENADYNE A4 negative pressure wound system [82]. This example further reinforces the potential therapeutic value of combining Manuka honey with VAC, highlighting the need for further clinical validation of this promising approach.

Additionally, an emerging concept in integration includes the HoneyCure hydrogel, which combines Manuka honey (UMF16), Melaleuca alternifolia (tea tree oil), Simmondsia chinesis (jojoba oil) and pectin (citrus origin). This formulation was investigated in a study that demonstrated an increased rate of epithelisation in dogs compared to standard care dressings [83]. Moreover, another study explored the incorporation of Manuka honey into cellulose acetate in the form of electrospun nanofibrous mats, using electrospinning, to combine the antibacterial properties of Manuka honey with the biocompatibility and regenerative support of the fibrous scaffold. In vitro results showed significant bacterial inhibition, improved wound breathability and enhanced cell compatibility, suggesting potential for wound healing applications [13]. A further study developed an innovative delivery approach using Manuka honey dissolvable microneedles (MHM) for the treatment of Methicillin‐resistant Staphylococcus aureus (MRSA) infections and to promote wound healing. The researchers employed an optimised low‐temperature, low‐pressure (vacuum) method to preserve honey's bioactivity while maintaining the structural integrity required for penetration into the skin, as conventional heat‐based processes could damage honey's beneficial components [27]. Key findings indicated that MHM was effective in killing MRSA at honey concentrations ≥ 10%, with vacuum‐prepared honey killing up to 8 × 10⁷ CFU/mL. Future applications of this innovation may include customising honey concentration based on wound type and incorporating other agents, such as antibiotics or aloe vera, for synergistic effects, which could significantly optimise wound care outcomes and enhance patient quality of life [27].

Moreover, fish skin grafts have been approved by the FDA, underscoring their potential as a promising approach for enhancing wound healing. However, research exploring the dual therapeutic potential of fish oil and Manuka honey in wound care remains limited, making this combination a potential area for future investigation [84]. Fish oil is rich in omega‐3 polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are known for their bioactive properties. These compounds help resolve inflammation, with EPA, in particular, exhibiting direct antibacterial activity against S. aureus , K. pneumoniae and E. faecalis [85]. The wound‐healing potential of fish oil alone has been demonstrated in animal models, where its application to rat wounds improved closure rates up to 92% compared to 52% in controls. In humans, a study investigated the effects of omega‐3 supplementation in patients with diabetic foot ulcers and reported a significant reduction in ulcer size, with no observed side effects, after administering 1000 mg of omega‐3 twice daily for 12 weeks [86, 87]. These findings suggest that combining the anti‐inflammatory and antibacterial actions of both fish oil and Manuka honey could offer synergistic benefits, encouraging further investigation in wound care research [84]. Another emerging therapeutic concept involves incorporating Manuka honey into tissue‐engineered scaffolds, specifically chitosan‐gelatin cryogels and hydrogels. A recent clinical trial published in 2023 found that cryogels containing 5% Manuka honey provided a balance between antibacterial effectiveness and scaffold integrity, without compromising biocompatibility [88]. These results may inform future scaffold development by highlighting the importance of optimising honey concentration to achieve both optimal healing efficacy and material stability.

Furthermore, a novel bioengineered wound dressing known as the BCMH sheet, composed of bioengineered collagen, Manuka honey and hydroxyapatite, has been studied in the treatment of chronic wounds [89]. In this study, 47 chronic wounds were treated, 20 with standard of care (SOC) and 27 with BCMH. Time to closure was significantly shorter in the BCMH group (7.4 weeks) compared to SOC (14.8 weeks), indicating nearly twice the rate of wound healing (p < 0.05). These findings highlight BCMH as a novel and promising therapeutic modality for managing chronic wounds [89].

9. Future Directions

Despite promising evidence supporting the use of Manuka honey in wound care, several strategic steps are needed to optimise its translation into standardised clinical practice. One important direction is the development of standardised dressings tailored to specific wound types, supported by clear clinical guidelines or classification systems to assist healthcare professionals in selecting the appropriate formulation. Future research should also focus on developing and evaluating novel delivery systems, such as hydrogels, microneedles and bioresponsive materials, as well as combination approaches like VAC therapy or fish oil‐infused dressings, to enhance therapeutic outcomes. Moreover, there is a notable gap in large‐scale randomised clinical trials comparing Manuka honey‐based dressings to current standards of care, such as synthetic dressings. This review aims to highlight the need for such studies to guide evidence‐based practice. Additionally, policy‐driven research is crucial for evaluating the cost‐effectiveness, accessibility and scalability of public health systems, particularly in low‐ and middle‐income countries (LMICs). Ultimately, integrating Manuka honey into structured wound care protocols, clinical training and medical education will be critical for ensuring consistent, informed and effective use across healthcare settings.

10. Conclusion

As discussed in this review, Manuka honey demonstrates significant potential as a multifunctional agent in wound care, providing antimicrobial, anti‐inflammatory and regenerative properties. Clinical studies support its use across various wound types, including diabetic foot ulcers, venous leg ulcers and pressure injuries, with advantages in managing infections, alleviating pain and improving healing outcomes. Despite these benefits, challenges remain. Variability in product quality, lack of standardised clinical guidelines and inconsistent trial designs limit its broader adoption. Its incorporation into standard practice is further hindered by regulatory oversight gaps and restricted accessibility in specific contexts. Developing precise procedures, maintaining quality control and conducting excellent clinical research, especially in high‐risk populations, should be the primary priorities going forward. By taking these steps, Manuka honey could potentially evolve from a supplemental therapy to a standardised, scientifically supported tool for wound care, offering a secure, all‐natural alternative in the face of rising antibiotic resistance.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.