Polyurethane-Based Wound Dressing Materials

Polyurethanes (PU) are among the most important sub-classes of the thermoplastic elastomer family. They can be prepared through step-growth polymerization of diisocyanates with diols [Ozkaynak et al., 2005]. During the reaction, hydrogen atoms of hydroxyl groups are transferred to nitrogen atoms of isocyanate groups. Polyurethanes contain different functional groups such as ether, amide and urea in addition to the urethane group. Changes in the R group and displacement of amide hydrogen produce multiple urethanes [Gültekin 2006, Howard et al., 2002, Lee et al., 2001; John et al., 2002; Zlatanic et al., 2003]. Materials with desired properties can be produced by making changes to the raw materials used during polyurethane synthesis [Gültekin 2006; Howard et al., 2002; Lee et al., 2001]. Polyurethane materials were first introduced in biomedical applications in the late 1950s. In recent years, biomaterials used for prosthetics, medical devices and equipment have shown rapid development. In particular, polyurethane has been widely used in the preparation of all types of medical devices such as tissue engineering, wound dressings and vascular stents due to its excellent biocompatibility and variable mechanical properties [Griesser, 1991; Lamba et al., 1997; Zdrahala and Zdrahala, 1999; Vermette et al., 2001].

2. Wound Dressing Materials

A wound can be defined as damage to or tearing of the skin surface caused by physical, chemical, mechanical and thermal injuries. When the skin is damaged, the resulting wound should be covered with an appropriate dressing to protect it from further contamination or trauma. The wound dressing material to be used to provide effective wound healing must be non-toxic and biologically compatible, allow gas exchange and protect the wound against external mechanical stress. The wound dressing material should also provide and maintain a moist environment over the injured skin; however, it is widely accepted that the healing process can be accelerated under these conditions [Gharibi et al., 2015; Boateng et al., 2008; Sweeney et al., 2012]. The general properties of an ideal wound dressing material are shown in Table 1 [Vowden et al., 2017, Harding et al., 2000, Harding et al., 2013]. Wound dressings can be examined in two categories: conventional and modern wound dressings. Examples of conventional wound dressings include products such as gauze, adhesive bandages, bandages, cotton, wool etc. Conventional dressings are dry dressings that prevent wound spread. Conventional dressings have been replaced with modern materials because they do not provide a moist environment for wound healing [Krishnan et al., 2019, Sezer et al., 2011, Dhivya et al., 2015, Viji et al., 2015]. Modern wound dressings typically rely on synthetic polymers and are classified as passive, interactive and bioactive. Passive dressings such as gauze and tulle are used to cover the wound. Thus, the wound can heal underneath.   Interactive wound dressings can be used in the form of films, foams, hydrocolloids and hydrogels [Dhivya et al., 2015, Viji et al., 2015, Mogoşanu et al., 2014]. Bioactive wound dressings are made from biopolymers such as collagen, hyaluronic acid and alginate. These wound dressings sometimes contain antimicrobials to enhance the wound healing process [Krishnan et al., 2019]. To give examples of wound dressing materials classified above: hydrocolloid wound dressings consist of absorbent components (typically carboxymethyl cellulose, pectin or gelatin). Hydrocolloids can absorb minimum to moderate amounts of drainage [Vowden et al., 2017]. They are preferred in pediatric wound care because they do not damage tissue when removed [Boateng et al., 2007]. Hydrogels are insoluble hydrophilic substances made from synthetic polymers. Because they are usually clear or transparent, the wound can be observed without removing the dressing material. As disadvantages, they can lead to bacterial proliferation, odor and exudate formation [Krishnan et al., 2019, Vowden et al., 2017]. Film dressings are flexible transparent polyurethane layers coated with an acrylic adhesive. These dressings are semi-permeable. They are easily applied to the patient's body. Because films are transparent, the wound can be easily observed. Film wound dressings are easy to use, inexpensive and semi-permeable to oxygen and water vapor [Vowden et al., 2017, Krishnan et al., 2019]. Foam wound dressings are semi-permeable and hydrophobic or hydrophilic with a bacterial barrier. They are polyurethane or silicone-based. They provide thermal insulation to the wound, create a moist wound environment, are non-adhesive and atraumatic, allowing removal of the dressing material. Foam dressings that release agents such as antimicrobials, moisturizers or anti-inflammatory analgesics to the wound also exist [Vowden et al., 2017]. Alginate wound dressings are a fibrous product obtained from brown seaweed. When alginate comes into contact with wound fluid, it forms a gel. This gel removes the fiber trapped in the wound and helps the dressing to be removed without excessive trauma. Furthermore, these wound dressings can absorb fluid up to 20 times their weight [Vowden et al., 2017, Krishnan et al., 2019]. Bioactive wound dressings include tissue-engineered products derived from natural tissues or artificial sources. Biomaterials play a vital role in normal wound healing and new tissue formation. These wound dressings have comprehensive healing activity. Antimicrobial agents can support the release of bioactive compounds such as insulin [Georgescu et al., 2017]. Topical antimicrobial agents currently used include products containing iodine (cadexomer iodine and povidone iodine), products containing silver (silver sulfadiazine and ionic silver-impregnated dressings) and products containing antiseptic substances such as polyhexamethylene [Vowden et al., 2017].

3. Polyurethane-Based Wound Dressing Materials

Polyurethanes are widely used as wound dressing materials due to their high biocompatibility, good permeability to oxygen and carbon dioxide, excellent mechanical strength and appropriate elasticity [Xu et al., 2013, Gharibi et al., 2015]. Polyurethane-based wound dressing materials reported in the literature are listed below. • Gultekin et al. fabricated a high biocompatibility polyurethane film based on linoleic acid, which is the main component of triglyceride oils [Gultekin et al., 2008]. The synthesized film is shown in Figure 1 [Gultekin et al., 2008].

Figure 1. Linoleic acid-based polyurethane film [Gultekin et al., 2008]

• An ideal antibacterial nanofiber wound dressing material was obtained by electrospinning a solution consisting of polyurethane, dextran and ciprofloxacin HCl (CipHCl) drug. • Polyurethane/siloxane-based electroactive, antibacterial and antioxidative wound dressing membranes were prepared by sol-gel condensation and in vitro test results showed that the prepared dressing material caused rapid healing in the wound model, as demonstrated by Gharibi et al. [Gharibi et al., 2015]. • Antimicrobial, endotoxin imidazolium-type cationic polyurethane foam wound dressings were prepared by Ding et al. [Ding et al., 2019]. Following in vivo results, the antimicrobial potential of the wound dressing material was proven. Figure 2 shows the synthesized antimicrobial, endotoxin imidazolium-type cationic polyurethane foam and a graphical summary [Ding et al., 2019].

Figure 2. Antimicrobial, endotoxin imidazolium-type cationic polyurethane foam and graphical summary [Ding et al., 2019]

• Polyurethane wound dressing material containing guanidine hydrochloride with biocompatible and antimicrobial properties was successfully obtained by Sahraro et al. [Sahraro et al., 2016]. • High-porosity polyurethane (PU) foams containing propolis extract at different concentrations were prepared as biocompatible, antimicrobial wound dressing materials. It was demonstrated in vivo that the prepared dressing materials resulted in improved skin wound healing [Khodobakhshi et al., 2019]. • Polyurethane foam wound dressing materials containing silver and asiaticoside (AS) with antimicrobial and non-cytotoxic properties were also developed. In an in vivo experimental wound model, it was experimentally proven that the wound repair efficiency of the dressing material was at high levels compared to the control [Namviriyachote et al., 2018]. • Jafari et al. obtained a biocompatible, antibacterial nanocomposite wound dressing material containing polyurethane/TiO2/chitosan [Jafari et al., 2018]. The obtained porous nanocomposite wound dressing material is shown in Figure 3 [Jafari et al., 2018]. These types of chitosan-based PU nanocomposites have high gas permeability.

Figure 3. Biocompatible, antibacterial nanocomposite wound dressing material containing polyurethane/TiO2/chitosan [Jafari et al., 2018]

• A low-cost foam wound dressing material was developed containing usnic acid (UA)-loaded polyaniline/polyurethane (PANI/PU). The biofilm inhibition and antibacterial efficacy of the composite were experimentally observed [R.dos Santos et al., 2018]. • A porous polyurethane-urea foam (PUUF) form wound dressing material was prepared. This prepared dressing material created a moist regional environment for wound healing and also absorbed abundant wound exudates. With hemostatic effect and low toxicity, it is an effective wound dressing material candidate for new robust wound healing. Figure 4 shows both the SEM image of the PUUF wound dressing foam material and the experimental wound healing image [Liu et al., 2017].

Figure 4. Polyurethane-urea foam form (PUUF) wound dressing material a) SEM image b) Time-dependent wound repair images in experimentally induced wound model [Liu et al., 2017]

• Polyurethane foam form wound dressing material saturated with hyaluronic acid and silver sulfadiazine has taken its place in the literature. In experimentally induced rat skin damage, wound size decreased by 77% healing in as short a time as 1 week [Cho et al., 2002]. • Antimicrobial, biocompatible polyurethane wound dressing materials were prepared from a new soya oil-based polyol blend containing neem oil and a 1,2-triazolium ring. The obtained material's excellent tensile strength supported mechanical protection of the wound throughout the healing process. Furthermore, it supports wound healing by providing and maintaining a moist and hygienic environment [Gholami et al., 2018]. • Biocompatible, antimicrobial polyurethane/siloxane membranes incorporating graphene oxide were prepared [Shams et al., 2017]. The presence of graphene oxide within cross-linked siloxane regions and polymeric chains strengthened the mechanical strength required for the wound dressing material. The combination of hydrophilic and hydrophobic regions in the wound dressing material backbone provided appropriate wound exudate management. It was demonstrated in a rat animal model that the wound dressing material containing graphene oxide supported wound healing with re-epithelialization, increased vascularization and collagen accumulation in healed tissue. The study is summarized in Figure 5 [Shams et al., 2017].

Figure 5. Graphical summary showing the effect of polyurethane/siloxane wound dressing material containing graphene oxide on tissue healing [Shams et al., 2017]

• To thermoplastic porous nanocomposite polyurethane; antibacterial biocompatible wound dressing materials that accelerate the re-epithelialization process in wounds were prepared by the addition of nano-silver and dopamine separately. Figure 6 shows both the SEM images of thermoplastic polyurethane/dopamine and thermoplastic polyurethane/nano-silver structures, material bending and wound healing images [Liu et al., 2018].

Figure 6. a) Dopamine-containing thermoplastic porous polyurethane b) nano-silver containing thermoplastic porous polyurethane structures' SEM images, material bending and wound healing images [Liu et al., 2018]

• Using electrospinning technique, a polyurethane-based wound dressing blended with copper sulfate nanofibers was developed. The SEM image of this wound dressing material is shown in Figure 7 [Jaganathan et al., 2018].

Figure 7. SEM image of polyurethane/copper sulfate nanocomposite [Jaganathan et al., 2018]

• Cinnamaldehyde-modified antibacterial microporous polyurethane wound dressing was obtained. [Kucinska-Lipka et al., 2019]. • Polyurethane hydrogel wound dressing foams also occupy an important place in the literature [Lundin et al., 2017]. • Water-based polyurethane/poly(N-vinylpyrrolidone) composite films were prepared by in situ polymerization in an aqueous medium. Following experimental results, Yoo et al. stated that this prepared film could have high potential as a new wound dressing material that provides and protects the moist environment needed to prevent crust formation and dehydration of the wound bed [Yoo et al., 2008]. • Semi-interpenetrating polymer networks containing poly(ε-caprolactone), lysine diisocyanate and 1,4-butanediamine at different ratios were synthesized through thermally initiated free radical polymerization. The transparency of the obtained networks in dry state and significant water absorption capacity at low temperature were investigated by Reddy et al. [Reddy et al., 2009].

4. Conclusion and Evaluation

The diversity of wound types has brought about diversity in wound dressings. Recent literature shows an increase in research on polyurethane-based wound dressings due to their high biocompatibility, good permeability to oxygen and carbon dioxide, excellent mechanical strength and appropriate elasticity properties. To polyurethane-based wound dressings, antimicrobial, antioxidative and growth factor agents that play important roles in wound treatment should be selected beyond existing literature to develop new technological advances in parallel with alternative wound dressings with multiple efficacy that increase wound healing rate. Prof. Dr. Süleyman Köytepe - İnönü University / Faculty of Arts and Sciences - Department of Chemistry Prof. Dr. Burhan Ateş - İnönü University / Faculty of Arts and Sciences - Department of Chemistry Dr. İdil Karaca Açarı - Malatya Turgut Özal University / Vahap Küçük Vocational School - Aquaculture Department İmren Özcan - İnönü University / Faculty of Arts and Sciences - Department of Chemistry

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