Volume 33 Number 4

Introduction

A great number of people with wounds must confront suffering, whether it be in terms of pain, expenses and time spent on treatment or opportunities missed during treatment.¹ Minimising wound healing time would be highly beneficial for patients. Wound healing is a multifaceted biological process that comprises several stages, including inflammation, proliferation, and remodeling.² Numerous preclinical and clinical investigations have demonstrated the beneficial effects of beta-glucans on wound healing.^3-10

Beta-glucans are a heterogeneous group of natural polysaccharides found in plants, bacteria, fungi and algae, which possess many biological effects, such as immunomodulatory, anticancer, antibacterial, antiviral, blood sugar lowering, cholesterol lowering and wound healing activities.^{11, 12} The healing process involves the activation of immune cells (such as macrophages), skin cells (such as keratinocytes), and connective tissue cells (such as fibroblasts) that express dectin-1 receptors on their cell surfaces¹³. This activation leads to the recruitment of inflammatory cells to the site of injury, promoting phagocytosis, cytokine production, cellular proliferation, the formation of new epithelium and collagen deposition, all of which work in concert to promote wound healing.^14-16 Moreover, beta-glucans effectively address challenges in healing hard-to-treat wounds, particularly during the inflammatory, proliferation and remodeling phases.^17-21

Chronic wounds usually result from underlying conditions, such as obesity or diabetes, which impair the process of normal wound healing.²² In chronic wounds, monocytes exhibit a proclivity to differentiate into inflammatory phenotype macrophages, exacerbating local inflammation,²³ while the reduced presence of anti-inflammatory macrophages impairs critical processes such as re-epithelialisation and angiogenesis ²⁴. Additionally, the dysfunction of neutrophils, including impaired chemotaxis and phagocytosis, further compromises the immune response, contributing to delayed wound healing.²⁵ Previous studies revealed that beta-glucan improves the healing of chronic ulcers by stimulating the infiltration of neutrophils during the inflammatory phase,^26,27 and enhancing the phagocytic activity of macrophages, thereby facilitating the removal of pathogens and tissue debris.^28,29 Beta-glucan has been shown to enhance cell proliferation and migration.³⁰ It promotes collagen synthesis through multiple pathways and modulates the ratio of collagen type I to collagen type III, which is beneficial in reducing scar formation.²¹ Additionally, several studies have demonstrated its potential in promoting angiogenesis by enhancing endothelial cell proliferation and migration via various signalling pathways, including HDAC5/MEF-2, PI3K/Akt/eNOS, Src/eNOS, AMPK/DAF16 and ERK1/2.^19,31,32 These mechanisms lead to increased levels of key cytokines, such as HIF-1α and VEGF,²⁰ which are critical for vascularisation and tissue integration. The overall mechanism of action of beta-glucan on wound healing is summarised in Figure 1.

 

Figure 1. The role of beta-glucans in each phase of wound healing.

 

To date, the precise mechanisms underlying beta-glucan’s effects on wound healing remain unclear. However, activation of dectin-1, a primary beta-glucan receptor, is thought to play a significant role in this process, as it has been identified in several non-immune cells, including human fibroblasts, keratinocytes,^14,33,34 and endothelial cells.^{19,20,31,35-38} Moreover, dectin-1 is proposed to contribute to angiogenesis through various pathways (Figure 2), including the stimulation of endothelial cell proliferation and migration. In addition to its role in wound healing, dectin-1 activation also supports peripheral nerve regeneration. In animal models of nerve injury, a correlation has been observed between dectin-1 activation and intraneural angiogenesis.³⁹ Additionally, a recent study explored the effects of beta-glucan in regenerative dentistry, aiming to identify supplements to repair injured dental pulp.⁴⁰ This study demonstrated that beta-glucan enhances dental pulp cell proliferation, migration and mineralisation. It also promotes integrin expression, collagen synthesis and mineralised matrix formation. Notably, previous evidence reported the expression of the dectin-1 receptor in human dental pulp,⁴¹ suggesting that these observed effects of beta-glucan may be mediated through this specific receptor. However, further investigation is needed to elucidate the precise pathways involved in beta-glucan’s actions.

 

Figure 2. The mechanism of beta-glucan-induced angiogenesis

 

More recent investigations have explored the use of beta-glucans for the treatment of hard-to-heal wounds, demonstrating that it exhibits good safety profiles and can facilitate the healing of cutaneous wounds in patients with chronic wounds or compromised healing, such as those with diabetes mellitus.^9,10,42 Due to the high costs and potential risks of antimicrobial resistance associated with conventional wound-care regimens, researchers have sought to develop alternative methods, including the use of natural bioactive extracts, to treat chronic wounds.⁴³ A recent clinical study evaluating the use of beta-glucan integrated gel for treating hard-to-heal wounds has reported promising results, showing that it can reduce healing time and be more cost-effective than standard treatments.⁴⁴ Furthermore, a higher percentage of wounds treated with beta-glucan gel completely healed compared to those receiving conventional care.^44,45 Taken together, these findings suggest that beta-glucan represents an effective and safe therapeutic option for the treatment of chronic wounds and offers financial advantages compared to conventional treatment methods.

Clinical investigations have demonstrated the efficacy of beta-glucans in promoting wound closure and reducing the cost of wound treatment.^44,46 Some studies have confirmed the beneficial effects of beta-glucans on wound healing, whether applied in the form of electrospun nanofibers or hydrogels.^10,47 Presently, commercial beta-glucan products are available in the form of semi-solid hydrogel that can be applied directly to the wound by finger. Consequently, wound dressings containing beta-glucans may represent a promising therapeutic approach for wound healing, with potential applications in medicine. However, reviews of studies on the effects of beta-glucan on wound healing in clinical settings still yield inconclusive results.^{9, 10, 42, 48, 49} This systematic review and meta-analysis aimed to investigate the effect of beta-glucan on wound healing.

Methods

This systematic review and meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.⁵⁰ This review was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42024464191).

Literature search

A comprehensive, systematic search was conducted in four international electronic databases including MEDLINE, Embase, Scopus, and Cochrane Library using keywords extracted from Medical Subject Headings such as “wound healing” and “beta-glucan” from the earliest to December 2024. For example, the search strategy was in the Scopus database, including (beta-glucan OR β-glucan OR beta glucan OR β glucan) AND (wound AND healing). To combine phrases, the Boolean operators “OR” and “AND” were used. Two researchers independently searched extensively.

Inclusion and exclusion criteria

The inclusion criteria for this review were clinical studies, including observational studies, clinical trials, and randomised controlled trials, which compared the duration of wound healing treated with any formulas of beta-glucan and any other procedures, irrespective of the type of wound. Duplicate publications were excluded. Studies in which complete data could not be obtained, duplicate studies, in vitro studies, animal experiments, conference abstracts, reviews, case series and case reports were excluded.

Articles screening and data extraction

Rayyan software was used to manage and organise the data during the screening process. Two researchers independently screened the study titles and abstracts, removed duplicate studies, and assessed them based on the predefined inclusion and exclusion criteria. While choosing the studies, any different opinions were resolved by discussion. Subsequently, the abstracts and full contents were examined to finalise the studies to be included. The extracted data included the following information: first author, publication year, sample size, types of beta-glucan, types of treatment used as control, the duration of healing, and types of wounds. Statistical data not reported in the articles.such as mean and standard deviation, were estimated using statistical method⁵¹ prior to meta-analysis.

Quality assessment

Newcastle-Ottawa quality assessment scales were used to independently evaluate the quality of the included observational studies by two researchers. There are eight items consisting of four for selection, one for comparability, and three for outcome. Each study could be awarded a maximum of one star for each numbered item within the selection and outcome. A revised Cochrane Risk of Bias tool for randomised trials (RoB2) was used for the randomised controlled trials that were included. The five domains of bias were assessed. They are: randomisation processes; deviations from intended inventions; missing outcome data; measurement of outcomes; and selection of the reported results.

Statistical analysis

Data analysis was carried out using STATA V.14 software. Odds ratio (OR) and 95% CI were obtained by mean and standard deviation. Heterogeneity was assessed using the I² statistic, with significant heterogeneity was defined as an I² greater than 50%. In the analysis, random effects models were used. Wound healing rates for patients treated with beta-glucan and for the non-beta glucan groups, along with sample sizes for each group from the studies, were sourced to report the healing rate difference between beta-glucan and non-beta glucan groups.

Results

The process of the literature search is shown in Figure 3. From four databases, 618 studies were found after an extensive search of electronic resources, however, due to duplication, 288 articles were excluded from the study. The remaining 330 studies were further subdivided into 317 studies that did not align with our inclusion criteria by screening title and abstract. The full texts of the remaining 13 studies were then thoroughly assessed. Among these, three studies were excluded due to inappropriate methodologies, and six studies were excluded due to incomparable outcomes. Ultimately, this systematic review and meta-analysis included four articles.^9,10,48,49​

 

Figure 3. Flow diagram of the studies selection process

 

Characteristics of the included studies

Among the four studies included in this analysis, two are randomised controlled trials (RCT) while the other two are retrospective cohort studies. These studies are categorised according to the type of wound examined: two studies focus on the healing of burn wounds, which are classified as acute wounds, and the other two investigate chronic wounds, which are likely attributable to diabetes mellitus. In each study, beta-glucan was used as a wound dressing, and compared with alternative dressings, such as Biobrane^® and methylcellulose. The average age of participants varied between studies, reflecting the differing etiologies of the wounds. The studies addressing acute wounds reported mean participant ages of 5.8 and 33.5 years, whereas those concerning chronic wounds reported mean ages of 54.5 and 61.7 years. Furthermore, the studies employed distinct outcome measures: those investigating acute wounds reported the time to complete healing (Table 1), while the studies focusing on chronic wounds assessed the number of wounds healed at a 12-week interval (Table 2).

 

Table 1. Baseline characteristics of the two studies included in the meta-analysis for acute wounds

 

Table 2. Baseline characteristics of the two studies included in the meta-analysis for chronic wounds

 

Quality assessment

The quality assessment using a revised Cochrane RoB2 tool reveals that both RCTs included had a high risk of bias (Supporting information, Table S1). Nevertheless, Newcastle-Ottawa quality assessment scales results were six and seven out of nine for the remaining two cohort studies, recruited as shown in Supporting information, Table S2.

After extracting the data, we conducted a comparative analysis of various outcome measurements that exhibit intersections across the studies. In the studies of acute wounds, particular emphasis was placed on assessing the time required for complete epitheliali sation. In the studies of chronic wounds, it was observed that the comparable outcome measure was the number of wounds healed at 12-weeks.

The effect of beta-glucan on chronic wound healing

The two studies of chronic wounds compared the number of wounds healed at 12-weeks from the beta-glucan and placebo treated groups. There was no heterogeneity among these two studies (I² = 0%, p = 0.99). A significantly increased number of healed wounds was observed in the beta-glucan group (OR = 2.14, 95% CI [1.31, 3.47]), p < 0.01; Figure 4).

 

Figure 4. Forest plot of the effect of beta-glucan on wound healing in chronic wounds.

 

In the study by Zykova et al¹⁰ of diabetic foot ulcers, beta-glucan treatment led to significantly higher healing rates compared to the control group. By week 12, 81% of wounds in the beta-glucan group were fully healed, compared to 66% in the control group; this advantage was sustained through week 24 (96% versus 75%). Beta-glucan also significantly accelerated wound size reduction, showing a 33% greater healing response by week 24 in chronic ulcers. The study by Hunt et al⁹ included a variety of chronic wound types, such as venous leg ulcers, pressure ulcers and diabetic foot ulcers, all of which had been non-healing for over eight weeks. Despite standard care wound healing outcomes were initially reported as wound size reduction percentages rather than the proportion of fully healed wounds. For consistency with the other included study, we used the 12-week data which reported that 81% of wounds in the beta-glucan group were fully healed, compared to 66% in the control group. Additionally, Hunt et al⁹ highlighted early healing progress, with 80% of wounds achieving ≥40% wound size reduction by week four in the beta-glucan group, compared to 62% in the control group. These findings demonstrate both the accelerated initial response and the sustained healing benefits of beta-glucan in chronic wounds. Patients treated with hydroigel reported high satisfaction and ease of use, with scores averaging 8.9 and 9.6 out of 10, respectively. The study also highlighted the cost-effectiveness of hydrogel, noting significant savings in patient care and wound management, making it a valuable option for chronic wound treatment, particularly in resource-limited settings.

The effect of beta-glucan on acute wound healing

On the other hand, two studies reported the effect of beta-glucan on time to complete epithelisation of acute wounds. Due to the lack of comparable data, the mean and standard deviation for the study by Lesher et al⁴⁸ were estimated from the reported median and range using a validated mathematical method.⁵¹ There was considerable heterogeneity among these two studies (I² = 76%, p = 0.04), but no significant relationship between use of beta-glucan and time-to-healed in this type of wound (MD= -1.70, 95% CI [-4.58, 1.18]), p = 0.25; Figure 5).

 

Figure 5. Forest plot of the effect of beta-glucan on wound healing in acute wounds.

 

In the study by Yang et al⁴⁹ comparing Biobrane^® and beta-glucan collagen (BGC) for split-thickness skin graft (STSG) donor sites, the results indicated no statistically significant difference in healing times between the two treatments. The Biobrane^® dressing facilitated an average healing time of 14 days, while BGC showed a comparable healing time of 14.5 days. These findings suggest that BGC performs similarly to Biobrane^® in terms of healing time for acute wounds. Similarly, the study by Lesher et al⁴⁸ evaluated the efficacy of Biobrane® versus BGC in treating pediatric partial-thickness burns and found that Biobrane^® significantly reduced the median healing time to 9 days, compared to 13 days with BGC. These findings suggest that Biobrane^® may provide a more effective and cost-efficient alternative for specific wound types.​

Discussion

This meta-analysis evaluated the effect of topical beta-glucan on wound healing across various wound types. The results of our meta-analysis indicate that the topical application of beta-glucan significantly increases the number of wounds healed at the 12-week mark by twofold compared to non-beta-glucan treatments in chronic wounds. This finding highlights its potential benefit in managing chronic conditions such as diabetic wounds and persistent infections. Enhancing the efficiency and reducing the duration of dermal wound healing is beneficial for patients suffering from wounds,⁵² especially chronic wounds.

Beta-glucan is a promising substance for wound healing due to its ability to promote cell growth, nerve regeneration and vasculari sation. This systematic review aimed to evaluate the clinical effects of beta-glucan on wound healing by incorporating various study designs, including randomised controlled trials and retrospective cohort studies while applying rigorous quality assessment. Although the results from the meta-analysis showed a significant improvement in healing rates for chronic wounds, the evidence supporting the clinical use of beta-glucan remains inconclusive. This is due to the limited number of clinical studies examining its efficacy, the variability in beta-glucan formulations, and the differences in wound types. Furthermore, an attempt was made to evaluate publication bias using the symmetry of the funnel plot. However, due to the limited number of studies, a formal analysis of publication bias could not be conducted (Figure S1). Similarly, an Egger’s test could not be performed for the same reason.

To critically analyse the limitations observed during data curation and meta-analysis, one of the main concerns is the variability in beta-glucan formulations used across studies. Currently, various formulations of beta-glucan are available on the market, derived from different sources such as mushrooms, yeast, barley and euglena. For instance, a previous study demonstrated that water-insoluble beta-glucan from Saccharomyces cerevisiae enhanced venous ulcer healing by increasing epithelial hyperplasia, angiogenesis and fibroblast proliferation.⁵³ Similarly, a bioactive beta-glucan gel has been shown to effectively manage ‘hard-to-heal’ wounds by promoting macrophage activation and angiogenesis.⁵⁴ Seo et al¹⁸ conducted a comparative study to evaluate the wound-healing effects of various beta-glucans and found that all tested formulations were non-toxic to fibroblasts and effectively promoted keratinocyte migration. Notably, beta-glucan derived from mushrooms demonstrated the most favourable effects on dermal wound healing, emphasising the varying levels of healing properties among different beta-glucan formulations. These findings suggest that the formulation and source of beta-glucan may significantly influence its efficacy in wound healing. High-quality randomised clinical trials are needed to validate this hypothesis in clinical settings.

Regarding different wound types, such as acute and chronic wounds, the results from the meta-analysis indicated that beta-glucan did not significantly promote healing in acute wounds. This finding may be explained by the fundamental differences in the healing mechanisms of acute and chronic wounds. Acute wound healing primarily depends on the rapid resolution of inflammation and epithelial migration—processes that may not require the immunomodulatory effects of beta-glucan⁵⁵. In contrast, beta-glucans ability to enhance macrophage activity and collagen synthesis is likely more relevant to the prolonged inflammatory phase characteristic of chronic wounds.^{3, 56}

Nonetheless, this review has certain limitations that should be addressed. First, the meta-analysis included only two studies for each wound type, limiting the robustness of the findings. Among these, one study in each analysis was of low quality based on the risk of bias assessment, while the other was a retrospective study rather than a randomised controlled trial, further reducing the level of evidence. Additionally, the studies included in the acute wound analysis exhibited significant heterogeneity (I² = 76%, p = 0.04), raising concerns about the reliability of pooled estimates. These factors significantly constrain the generalisability of the results and necessitate caution in interpreting the findings. Future research should prioritise well-designed randomised controlled trials with larger sample sizes and standardised reporting to strengthen the evidence base.

This distinction emphasises the need for future research to explore beta-glucan formulations tailored to specific wound types. Subsequent studies could also investigate its effects on wound healing across diverse tissue types or its potential applications in regenerative medicine and dentistry. Such investigations may establish beta-glucan as a preferred pharmaceutical option for optimising treatment efficacy and improving patient outcomes, ultimately enhancing the quality of life for individuals with complex wound healing needs.

Conclusions

Topical application of beta-glucan has been shown to significantly increase healing rates at 12 weeks. While these findings suggest that topical beta-glucan may enhance healing responses in chronic wounds, further high-quality randomised clinical trials are needed to confirm its efficacy and identify the most effective formulations for clinical use.

Author contribution

Conceptualisation: T Somboonchokephisal and T Srisuwan
Methodology: S Saokaew
Investigation: T Somboonchokephisal; S Techachan
Data Analysis and Interpretation: T Somboonchokephisal
Writing – Original Draft: T Somboonchokephisal, T Kaokai
Writing – Review and Editing: T Somboonchokephisal, S Kanchanasurakit and T Srisuwan
Supervision: T Srisuwan
Funding Acquisition: T Srisuwan

Conflict of interest

The authors declare no conflict of interest.

Ethics statement

An ethics statement is not applicable.

Funding

The research grant for this project was partially supported by the Fundamental Fund of Thailand Science Research and Innovation (TSRI), and the Faculty of Dentistry Research Funding, Chiang Mai University, Chiang Mai, Thailand.

Author(s)

Thanutham Somboonchokephisal¹, Supitchaya Techachan¹, Taweesak Kaokai²,
Surasak Saokaew^3,4,5,6, Sukrit Kanchanasurakit^3,4,7,8, Tanida Srisuwan¹*
¹Department of Restorative Dentistry and Periodontology, Chiang Mai University, Chiang Mai, Thailand
²Dental Department, Phobphra Hospital, Tak, Thailand
³Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences (SPS), University of Phayao, Phayao, Thailand
⁴Unit of Excellence On Clinical Outcomes Research and IntegratioN (UNICORN), SPS, University of Phayao, Thailand
⁵Unit of Excellence On Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Thailand
⁶Division of Social and Administration Pharmacy, School of Pharmaceutical Sciences, University of Phayao, Thailand
⁷Division of Clinical Pharmacy, School of Pharmaceutical Sciences, University of Phayao, Thailand;
⁸Division of Pharmaceutical Care, Department of Pharmacy, Phrae Hospital, Phrae, Thailand

*Corresponding author email tanida_srisuwan@yahoo.com

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Supplementary Information

The effect of beta-glucan on duration of wound healing:
A systematic review and meta-analysis

Publication bias assessment

Figure S1. Funnel plot of the result of the effect of beta-glucan on the healing rate of acute (A) and chronic wounds (B).

 

Quality assessment of included studies

Table S1. Quality assessment of the two randomised controlled trials.

 

Table S2. Quality assessment of cohort studies included.