Multi-layer dressing made of laminated electrospun nanowebs and cellulose-based adhesive for comprehensive wound care

Abstract

In this work, multi-layer wound dressing was made of laminated layers of electrospun fibers supported by adhesive sheet. Graft copolymerization of methyl methacrylate (MMA) and 2-Ethyl-1-hexyl acrylate (EHA) onto carboxymethyl cellulose (CMC) was conducted to obtain an adhesive sheet with 1.52 (N/cm²) loop tack, 1.7 (N/cm) peel strength and 25 s shear strength. Diclofenac sodium, anti-inflammatory drug, was loaded to the adhesive sheet with encapsulation efficiency 73%.

The contact layer to wound was made of synthesized anti-bleeding agents, chitosan iodoacetamide (CI) loaded into electrospun polyvinyl alcohol (PVA) fibers. It was fabricated from fiber diameter 300 nm by electrospinning of 5% wt/v of CI (D.S. 18.7%) mixed with 10% wt/v PVA, at 20 kV and 17 cm airgap. The second, pain-relief layer was fabricated by encapsulating up to 50% wt/wt of capsaicin into gelatin nanofibers (197 nm) crosslinked by glyoxal. The third, antimicrobial layer was fabricated from PVA electrospun fibers loaded with 2% wt/wt gentamicin. Biocompatibility test showed insignificant adverse effects of the fabricated layers on fibroblast cells. Animal test on rat showed accelerated wound healing from 21 to 7 days for the multi-layer dressing. Histopathological findings corroborated the intactness of the epidermis layer of the treated samples.

Introduction

Shortcomings in trauma care, on-site, are considered as the major cause of mortality and impaired quality of life. Successful techniques for trauma care such as junctional tourniquets, and blood-transfusion equipment need well-trained medics available within minutes immediately after an injury [1]. Troops in front lines, those injured in car wrecks and others who are severely wounded may not have enough time to be served quickly and effectively by those tools. According to a US-military medical report [1], nearly a quarter of the American soldiers killed in action over the past 10 years, lost their lives of wounds that can be treated. Therefore, providing a suitable wound dressing, produced using affordable local resources and handleable to untrained caregivers for accelerating wound healing, could save many lives.

An understanding of the basic physiology of wound healing process reveals that the healing process comprises of separated and overlapping four phases, namely hemostasis, inflammatory, proliferation, and remodeling, which take place successively [2].

As a result, the US Defense Department has authorized three hemostatic agents: zeolite dressing called “Quikclot”, chitosan dressing called “Hemcon” and the fibrin American Red Cross dressing. However, each product has disadvantages and drawbacks as zeolite, an effective hemostatic agent, may cause major thermal injuries, remain as a foreign body in open wounds and are toxic in the eye or lung. Hemcon bandages, a lyophilized chitosan foam, are not large enough or sufficiently flexible to fill large wounds and work best on limited flat surfaces. The fibrin American Red Cross dressing is highly effective but also limited in availability and costs 100 times over Quikclot and 10 times over Hemcon [3].

Therefore, many other products have been developed and commercialized in the market to control bleeding as hemostatic agents [[4], [5], [6]]. For instance, chitosan-based films [3,[7], [8], [9]], oxidized cellulose [10], zinc paste [11], silver nitrate [12] and aluminum chloride [13] have been used as hemostatic agents. However, many others have been employed to provide antimicrobial protection such as quaternary ammonium salts [14], honey [15], iodine complexes [16], and antibiotic agents [17]. However, each product has benefits and drawbacks and can only serve one phase in the wound healing process. In some cases, chitosan for instance, can be used as both a hemostatic agent and an antimicrobial agent [18].

On the other hand, drug delivery systems have been recently employed as a new pharmacological approach to improve the efficacy and the safety of drug administration. Vesicles, micelles, electrospun fibers [[19], [20], [21], [22], [23]], emulsions [24], microspheres [[25], [26], [27]], hydrogels [[28], [29], [30], [31], [32]], and biodegradable nanoparticles [33,34] have been extensively studied [35] as carriers for biological substances such as drugs, genes, proteins, and etc.

Few studies have been devoted to prepare laminated material comprising an absorbent substrate and a sheet-shaped carrier [36] loaded with biological active substances. Such a new generation of medicated dressings has been reported to overcome some of the disadvantages of the topical application of pharmaceutical agents. Hydrogels, hydrocolloids, alginates, polyurethane foam/films and silicon gels have been used to deliver active agents to the wound bed [37]. The latter materials have been constructed to trap a single compound serving one part of the targeting process and there is no single agent that can serve the entire set of phases of the wound healing process, all at once. Meanwhile, it is difficult to combine two or more wound healing agents together in one substrate and to provide a dressing that can be placed on wounds for a few days without the need for replacement or cleaning of the wound bed. As a result, none has been reported on producing multifunctional wound dressing for comprehensive wound care.

In this work, a laminated multifunctional electrospun dressing using different electrospun mats was prepared based on different electrospun fibers supported by an adhesive sheet. Cytotoxicity tests and pre-clinical studies on a rat wound model were conducted to reveal the wound dressing potentials.