Chronic wounds are often recalcitrant to treatment due to high microbial bioburden and the problem of microbial resistance. Silver is a broad spectrum natural antimicrobial agent with wide applications extending to proprietary wound dressings. Recently silver nanoparticles have attracted attention in wound management. In the current study, the green synthesis of nanoparticles was accomplished using a natural reducing agent, curcumin which is a natural polyphenolic compound, well known as a wound healing agent. The hydrophobicity of curcumin was overcome by its microencapsulation in cyclodextrins. This prediction study demonstrates the production, characterisation of silver nanoparticles using aqueous curcumin:hydroxypropyl-β-cyclodextrin complex and loading them into bacterial cellulose hydrogel with moist wound healing properties. These silver nanoparticle-loaded bacterial cellulose hydrogels were characterised for wound management applications. In addition to high cytocompatibility, these novel dressings exhibited antimicrobial activity against three representative wound infecting pathogenic microbes Staphylococcus aureus, Pseudomonas. aeruginosa and Candida auris.

Bacterial cellulose (BC) is an extracellular polymer produced by Komagateibacter xylinus, which has been shown to possess a multitude of properties, which makes it innately useful as a next-generation biopolymer. The structure of BC is comprised of glucose monomer units polymerised by cellulose synthase in β-1-4 glucan chains which form uniaxially orientated BC fibril bundles which measure 3–8 nm in diameter. BC is chemically identical to vegetal cellulose. However, when BC is compared with other natural or synthetic analogues, it shows a much higher performance in biomedical applications, potable treatment, nano-filters and functional applications. The main reason for this superiority is due to the high level of chemical purity, nano-fibrillar matrix and crystallinity. Upon using BC as a carrier or scaffold with other materials, unique and novel characteristics can be observed, which are all relatable to the features of BC. These properties, which include high tensile strength, high water holding capabilities and microfibrillar matrices, coupled with the overall physicochemical assets of bacterial cellulose makes it an ideal candidate for further scientific research into biopolymer development. This review thoroughly explores several areas in which BC is being investigated, ranging from biomedical applications to electronic applications, with a focus on the use as a next-generation wound dressing. The purpose of this review is to consolidate and discuss the most recent advancements in the applications of bacterial cellulose, primarily in biomedicine, but also in biotechnology.

An increase in antifungal resistance has seen a surge in fungal wound infections in patients who are immunocompromised resulting from chemotherapy, disease, and burns. Human pathogenic fungi are increasingly becoming resistant to a sparse repertoire of existing antifungal drugs, which has given rise to the need to develop novel treatments for potentially lethal infections. Bacterial cellulose (BC) produced by Gluconacetobacter xylinus has been shown to possess many properties that make it innately useful as a next-generation biopolymer to be utilised as a wound dressing. The current study demonstrates the creation of a pharmacologically active wound dressing by loading antifungal agents into a biopolymer hydrogel to produce a novel wound dressing. Amphotericin B is known to be highly hepatotoxic, which reduces its appeal as an antifungal drug, especially in patients who are immunocompromised. This, coupled with an increase in antifungal resistance, has seen a surge in fungal wound infections in patients who are immunodeficient due to chemotherapy, disease, or injury. Antifungal activity was conducted via Clinical & Laboratory Standards Institute (CLSI) M27, M38, M44, and M51 against Candida auris, Candida albicans, Aspergillus fumigatus, and Aspergillus niger. This study showed that thymoquinone has a comparable antifungal activity to amphotericin B with mean zones of inhibition of 21.425 ± 0.925 mm and 22.53 ± 0.969 mm, respectively. However, the mean survival rate of HEp-2 cells when treated with 50 mg/L amphotericin B was 29.25 ± 0.854% compared to 71.25 ± 1.797% when treated with 50 mg/L thymoquinone. Following cytotoxicity assays against HEp-2 cells, thymoquinone showed a 71.25 ± 3.594% cell survival, whereas amphotericin B had a mean cell survival rate of 29.25 ± 1.708%. The purpose of this study was to compare the efficacy of thymoquinone, ocimene, and miramistin against amphotericin B in the application of novel antifungal dressings.

The need for more advantageous and pharmaceutically active wound dressings is a pressing matter in the area of wound management. In this study, we explore the possibility of incorporating thymoquinone within bacterial cellulose, utilising cyclodextrins as a novel method of solubilising hydrophobic compounds. The thymoquinone was not soluble in water, so was incorporated within hydroxypropyl-β-cyclodextrin before use. Thymoquinone: hydroxypropyl-β-cyclodextrin inclusion complex produced was found to be soluble in water up to 7% (w/v) and was stable with no crystal formation for at least 7 days with the ability to be loaded within the bacterial cellulose matrix. The inclusion complex was found to be thermally stable up to 280 °C which is far greater than the production temperature of 80 °C and was stable in phosphate-buffered saline and extraction solvents in permeation and dose experiments. The adhesion properties of the Thymoquinone: hydroxypropyl-β-cyclodextrin loaded bacterial cellulose dressings were tested and found to be 2.09 N. Permeation studies on skin mimicking membrane Strat-M showed a total permeated amount (0–24 h) of 538.8 µg cm⁻² and average flux after a 2 h lag of 22.4 µg h⁻¹ cm⁻². To the best of our knowledge, the methods outlined in this study are the first instance of loading bacterial cellulose with thymoquinone inclusion complex with the aim of producing a pharmaceutically active wound dressing.

Wounds from various sources such as burns and ulcers which have been in a prolonged state of inflammation and rubor, both exudative and non-exudative, are decidedly prone to becoming infected by various opportunistic and commensal microorganisms, both bacterial and fungal due to the warm moist environment at the wound site (Que et al.,2019). The typical approach in treating these wounds is to reduce the level of infection and inflammation, thus encouraging an appropriate environment for successful re-epithelisation resulting in faster healing of the wound. Bacterial cellulose (BC) is an ideal material to produce wound dressings due to the intrinsic properties such as; high chemical stability, high tensile strength and flexibility, large water holding capacity, permeable to gases and liquids, and excellent biocompatibility (Gupta et al., 2016; Gupta et al.,2017, Wahid et al., 2019). In this study, BC produced by Komagataeibacter xylinus was used as a hydrogel matrix and loaded with a well-known antimicrobial agent- curcumin encapsulated in solubility enhancing carriers, hydroxypropyl- β-cyclodextrin (CUR:HPβCD) (Abbas et al., 2019, Gupta et al., 2019). BC was loaded with 2% (w/v) aqueous CUR:HPβCD inclusion complex under constant agitation at 170 rpm at 20°C (room temperature) for 24 hours. Antimicrobial activity was tested against two representative organisms: Candida albicans and Staphylococcus aureus by disc diffusion method. We have previously reported the antibacterial activity of CUR:HPβCD-loaded BC (Gupta et al., 2019). The current study is an extension of our ongoing research where we made an attempt of testing the anti-fungal activity of CUR:HPβCD-loaded BC and compared it with anti-bacterial activity. 8mm discs were aseptically cut and placed on TSA plates seeded with overnight cultures of one of the microorganisms under investigation and incubated at 37°C for 24 hours. The results indicated that C. albicans and S. aureus were both susceptible to CUR:HPβCD inclusion complex with an average zone of inhibition of 12.25±2.2mm and 11±1.2mm respectively (n=4, ±=SD, p <0.05). The results against S. aureus are in accordance with our previously reported findings (Gupta et al., 2019). Current findings support the wound management applications of CUR:HPβCd-loaded BC hydrogels for chronic wounds. References Abbas, M., Hussain, T., Arshad, M., Ansari, A., Irshad, A., Nisar, J., Hussain, F., Masood, N., Nazir, A. and Iqbal, M. (2019). Wound healing potential of curcumin cross-linked chitosan/polyvinyl alcohol. International Journal of Biological Macromolecules, 140, pp.871-876. Gupta, A., Keddie, D., Kannappan, V., Gibson, H., Khalil, I., Kowalczuk, M., Martin, C., Shuai, X. and Radecka, I. (2019). Production and characterisation of bacterial cellulose hydrogels loaded with curcumin encapsulated in cyclodextrins as wound dressings. European Polymer Journal, 118, pp.437-450. Gupta, A., Low, W., Britland, S., Radecka, I. and Martin, C. (2017). Physicochemical characterisation of biosynthetic bacterial cellulose as a potential wound dressing material. British Journal of Pharmacy, 2(2), pp.S37-S38. Gupta, A., Low, W., Radecka, I., Britland, S., Mohd Amin, M. and Martin, C. (2016). Characterisation and in vitro antimicrobial activity of biosynthetic silver-loaded bacterial cellulose hydrogels. Journal of Microencapsulation, 33(8), pp.725-734. Que, A., Nguyen, N., Do, N., Nguyen, N., Tran, N. and Le, T. (2019). Infection of burn wound by Aspergillus fumigatus with gross appearance of fungal colonies. Medical Mycology Case Reports, 24, pp.30-32. Wahid, F., Hu, X., Chu, L., Jia, S., Xie, Y. and Zhong, C. (2019). Development of bacterial cellulose/chitosan based semi-interpenetrating hydrogels with improved mechanical and antibacterial properties. International Journal of Biological Macromolecules, 122, pp.380-387.