Preparation and evaluation of a novel wound dressing sheet comprised of β-glucan–chitosan complex

https://doi.org/10.1016/j.reactfunctpolym.2010.07.014Get rights and content

Abstract

A transparent wound dressing sheet was obtained by forming a complex between β-glucan and chitosan (CS). These materials were chosen for their biocompatible, bioabsorbable, and biodegradable properties, and they were expected to promote the therapeutic efficacy of the dressing by increasing the wound healing response. The therapeutic efficacy of the β-glucan–CS complex sheet as a wound dressing was evaluated in wounds created on the dorsal surfaces of mice. β-glucan–CS complex sheets demonstrated therapeutic efficacies comparable or superior to that of Beschitin®W, a commercial wound dressing made from CS. Additionally, the β-glucan–CS complex sheet did not dissolve during the application period, did not adhere to wounds, and was easy to remove. Cumulatively, these results indicate that β-glucan–CS complex sheets are a promising new wound dressing product.

Introduction

Traditional wound dressings, including absorbent cotton and gauzes, have been used to absorb wound exudates and thus maintain wound dryness and to prevent the invasion of bacteria into the wound. However, wound healing occurs more rapidly and successfully when epithelial cells can move unimpeded – in other words, when wounds are moist, receive adequate oxygen circulation to facilitate regeneration of cells and tissues, and are protected from bacterial invasions [1], [2]. In recent years, many types of wound dressings and devices have targeted different aspects of the wound healing process. These dressings can be classified according to their function (e.g., absorbing moisture, facilitating debridement, functioning as an antibacterial, acting as an occlusive, adhering to the wound, enhancing healing, or mitigating pain), the materials from which they are constructed, including synthetic polymers (e.g., polyurethane, polymethacrylate, polyvinylpyrrolidone, or carboxymethylcellulose) and biomaterials (e.g., collagen, alginates, chitin, chitosan, or hyaluronic acid), and the physical form of the dressing (e.g., hydrocolloid, ointment, fiber, film, foam, or gel) [3]. It is important to have variety in dressing functions, materials, and forms, as they are needed for use on many different types of wounds (e.g., acute or chronic, different depths and areas, and different parts of body), for patients in a variety of health states, and for wounds at different stages of the healing process.

One material that has shown promise as a component of dressings is β-glucan, a polysaccharide comprised of β-linked d-glucose molecules. A variety of β-glucans have been isolated from various sources, such as fungi, baker’s yeast, barley, and seaweed. The physicochemical properties of β-glucans differ depending on characteristics of their primary structure, including linkage type, degree of branching, molecular weight, and conformation (e.g., triple helix, single helix, and random coil structures) [4]. Recent reports have shown that β-glucan plays a significant role in treating cancer, lowering blood cholesterol levels, reducing acute inflammatory responses, and acting as a biological response marker to enhance the immune system [5], [6], [7], [8]. For instance, β-(1,3–1,6)-d-glucans isolated from black yeast (Aureobasidium pullulans) has attracted the attention of scientists because it enhances the immune system; in particular, it activates macrophages and accelerates the production of cytokines such as TNF-α, IL-6, and IL-12 [4], [9].

Another material that shows promise as a component of dressings is chitosan (CS), a plentiful natural polysaccharide isolated mainly from crab shells. CS is comprised of linearly (1–4)-linked N-acetyl glucosamine and glucosamine residues. The physicochemical and biological properties of CS are influenced by its molecular weight and degree of deacetylation. Additionally, CS is non-toxic, biocompatible, and biodegradable [10], [11]. Numerous studies have demonstrated that CS is an effective and safe vehicle for drug delivery [12], [13], [14], [15], [16] and can be used for implantable biomedical applications [17]. Furthermore, CS has also been reported to act as an antioxidant [18], [19], to have analgesic effects on inflammatory pain [20], and to accelerate wound healing by activating and infiltrating polymorphonuclear cells and basic fibroblast growth factors in wounds [21], [22]. In vitro studies have shown that CS can accelerate the proliferation of keratinocytes [23].

Traditional dressings have been made of animal materials, such as pigskin, which are biocompatible but induce immune reactions in humans and may be rejected. Also, dressings have been comprised of various synthetic polymers, which may become incorporated into granulation tissue, thereby remaining in the body once the wound is healed. As these examples indicate, dressings must contain a fine balance of characteristics; they should facilitate the quick and successful healing of wounds, be safe and biocompatible, and, if possible, contain a curative to enhance the healing process.

To meet this need, we have created a novel wound dressing from a complex of β-glucan and CS. This dressing is biocompatible, bioabsorbable, biodegradable, and has therapeutic efficacy. Here, we present the methods by which this dressing was fabricated, and we describe the results of an investigation of the dressing’s physiological properties and therapeutic efficacy when applied to all skin layer defects on a murine test subject.

Section snippets

Materials

β-(1,3–1,6)-d-Glucan isolated from black yeast (Aureobasidium pullulans) was donated by ADEKA Co. (Tokyo, Japan). CS was donated by Ajinomoto Co. Inc. (Tokyo, Japan), Koyo Chemical Co. Ltd. (Osaka, Japan), Kyowa Tecnos Co. Ltd. (Tiba, Japan), Nipponkayaku Foodtechno Inc. (Gunma, Japan), Yaegaki Bio-industry, Inc. (Hyogo, Japan), and Yaizu Suisankagaku Industry Co. Ltd. (Shizyoka, Japan), or purchased from Katokichi Co. Ltd. (Kagawa, Japan). Beschitin®W, a wound dressing material made from CS,

Properties of the β-glucan–CS complex sheet

Dissolution of the CS suspended in the β-glucan solution was aided by immersion in an acetic acid buffer solution, which triggered salt formation between some amino groups of CS and acetic acid. These salts dissociated after contacting β-glucan, leading to formation of a hydrogel sheet comprised of β-glucan–CS complex. The final product, a colorless and transparent sheet, was obtained by drying the hydrogel at room temperature. If β-glucan solution and CS acetic acid solution were mixed, then

Conclusion

A transparent, biocompatible, bioabsorbable, and biodegradable sheet was manufactured by forming a complex of β-glucan with CS. Biodegradation of the sheet leads to the release of β-glucan and CS, which accelerates wound repair by activating macrophages and cytokines. By manipulating the properties of the CS used to create the sheet, we found that we were able to control the biodegradation of the sheet, thereby adjusting the release rate of β-glucan and CS. The complex sheet did not dissolve

References (26)

  • J.S. Boateng et al.

    J. Pharm. Sci.

    (2008)
  • P. Sai K. et al.

    Burns

    (2000)
  • G.D. Ross et al.

    Immunopharmacology

    (1999)
  • K. Tomihata et al.

    Biomaterials

    (1997)
  • H. Onishi et al.

    Biomaterials

    (1999)
  • S.R. Jameela et al.

    Biomaterials

    (1995)
  • K. Oungbho et al.

    Int. J. Pharm.

    (1997)
  • E. Khor et al.

    Biomaterials

    (2003)
  • J. Je et al.

    Food Chem. Toxicol.

    (2004)
  • Y. Okamoto et al.

    Carbohyd. Polym.

    (2002)
  • H. Ueno et al.

    Biomaterials

    (1999)
  • C. Chatelet et al.

    Biomaterials

    (2001)
  • D. Queen et al.

    Int. Wound J.

    (2004)
  • Cited by (41)

    • Fungal exopolysaccharides: Properties, sources, modifications, and biomedical applications

      2022, Carbohydrate Polymers
      Citation Excerpt :

      PUL is made by several strains of Aureobasidium pullulans (Selvasekaran et al., 2021) which contains α-(1, 6)-linked maltotriose units, as a distinctive linkage configuration is considered to be responsible for the structural flexibility and solubility of PUL, leading to the unique film- and fiber-forming characteristics (Leathers, 2003). PUL is water-soluble and has wound healing and antibacterial activities (Kofuji et al., 2010; Singh et al., 2008). It is instantly biodegradable and is greatly resistant to temperature (its decomposition happens above 200 °C with no discharge of toxic gases) (Verma et al., 2020).

    • Biopolymer-based films and membranes as wound dressings

      2020, Biopolymer Membranes and Films: Health, Food, Environment, and Energy Applications
    • Electrospun Schizophyllan/polyvinyl alcohol blend nanofibrous scaffold as potential wound healing

      2019, International Journal of Biological Macromolecules
      Citation Excerpt :

      During wound healing, they attach tightly to a receiver on the fibroblast's surface and lead to the generation of an extracellular matrix. The polysaccharides have been studied for their biocompatibility as electrospun, film scaffolds, and hydrogel, which can be utilized for wound dressing aims [12–21]. There exist some rigid polysaccharides in nature that can self-assemble into ordered hierarchical structures.

    View all citing articles on Scopus
    View full text