bs_bs_banner Minireview Bacterial cellulose: a versatile biopolymer for wound dressing applications Raquel Portela,1 Catarina R. Leal,2,3 Pedro L. acquire antibacterial response and possible local Almeida2,3,**† and Rita G. Sobral1,*† drug delivery features. Due to its intrinsic versatility, 1Laboratory of Molecular Microbiology of Bacterial BC is the perfect example of a biotechnological Pathogens, UCIBIO@REQUIMTE, Departamento de response to a clinical problem. In this review, we Ciencias^ da Vida, Faculdade de Ciencias^ e Tecnologia, assess the BC main features and emphasis is given Universidade Nova de Lisboa, 2829-516 Caparica, to a specific biomedical application: wound dress- Portugal. ings. The production process and the physical– 2Area Departamental de Fısica, ISEL - Instituto Superior chemical properties that entitle this material to be de Engenharia de Lisboa, Instituto Politecnico de used as wound dressing namely for burn healing are Lisboa, Rua Conselheiro Emıdio Navarro 1, P-1959-007 highlighted. An overview of the most common BC Lisboa, Portugal. composites and their enhanced properties, in partic- 3CENIMAT/I3N, Departamento de Ciencia^ dos Materiais, ular physical and biological, is provided, including Faculdade Ciencias^ e Tecnologia, Universidade Nova de the different production processes. A particular Lisboa, 2829-516 Caparica, Portugal. focus is given to the biochemistry and genetic manipulation of BC. A summary of the current mar- keted BC-based wound dressing products is pre- Summary sented, and finally, future perspectives for the usage of BC as wound dressing are foreseen. Although several therapeutic approaches are avail- able for wound and burn treatment and much pro- gress has been made in this area, room for Introduction improvement still exists, driven by the urgent need Cellulose is the most abundant naturally occurring poly- of better strategies to accelerate wound healing and mer obtained from renewable sources. It consists of a recovery, mostly for cases of severe burned linear homopolysaccharide composed by b-D-glucopyra- patients. Bacterial cellulose (BC) is a biopolymer nose units linked by b-1,4 glycosidic bonds (Cannon and produced by bacteria with several advantages over Anderson, 1991). The most commercially exploited natu- vegetal cellulose, such as purity, high porosity, per- ral source of cellulose is wood, due to its high availability meability to liquid and gases, elevated water uptake that meets the demands of the paper industry (Klemm capacity and mechanical robustness. Besides its et al., 2005). However, a variety of plants also contains fi biocompatibility, BC can be modi ed in order to large amounts of cellulose, such as hemp, flax or cotton (Fernandes et al., 2017). In addition to these sources, Received 31 October, 2018; revised 11 February, 2019; accepted cellulose can be produced, among others, by seaweed, 12 February, 2019. fungi and some species of bacteria, being the most note- For correspondence. *E-mail [email protected]; Tel. (+351) 212948530; worthy the non-pathogenic bacteria of the genus Koma- Fax (+351) 212948530. **E-mail [email protected]; Tel. (+351) 218317135; Fax (+351) 218317138. gateibacter, such as K. xylinus, former Acetobacter and † These authors contributed equally. Gluconacetobacter (Brown, 1886). Several strains of – Microbial Biotechnology (2019) 12(4), 586 610 K. xylinus produce extracellular cellulose forming a bio- doi:10.1111/1751-7915.13392 Funding Information film of varying thickness with the purpose of maintaining This work is funded by FEDER funds through the COMPETE 2020 a high oxygenation of the colonies near the surface, – Program, and National Funds through FCT Portuguese Foundation which serves as a protective barrier against drying, natu- for Science and Technology under the projects: POCI-01-0145- FEDER-007688 (Reference UID/CTM/50025/2013), UID/Multi/04378/ ral enemies and radiation. 2019 (Unidade de Ciencias^ Biomoleculares Aplicadas – UCIBIO) and Besides being biodegradable, non-toxic and biocompat- fi co- nanced by FEDER funds through PT2020 Partnership ible, one of the major advantages of bacterial cellulose Agreement (POCI-01-0145-FEDER-07728); PTDC/FIS-NAN/0117/ 2014; and PTDC/BIA-MIC/31645/2017. (BC) over vegetal cellulose is its unique native purity that ª 2019 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Bacterial cellulose for wound dressing 587 allows for its direct utilization. It is chemically equivalent to In 2016, the American Burn Association reported plant cellulose, but it is free of by-products such as lignin, 486 000 burn-related injuries receiving medical treatment pectin, hemicellulose and other constituents of lignocellu- in the United States, including 40 000 hospitalizations losic materials (Klemm et al., 2001; Rahman and Netra- (American Burn Association, 2016). Although the survival vali, 2016). It is obtained by fermentation and only rate has considerably increased to 96.8%, severe burn contains microbial cells, nutrients and other secondary injuries are difficult to manage, requiring extended hospi- metabolites that can be easily removed, yielding highly tal stays and expensive treatment choices (American pure cellulose. Although BC molecular formula is similar Burn Association, 2016). The current standard of care to plant cellulose, BC mechanical and physical outstand- for closing burn wounds and preventing wound sepsis ing properties emerge from its unique 3D structure that dif- includes early surgical excision of the damaged necrotic fers significantly from that of vegetal source, as BC tissue followed by complete coverage of the exposed aggregates to form long fibrils of 1.5 nm width, providing area (Rowan et al., 2015). higher surface area, elasticity, resistance and flexibility. Another relevant skin condition for wound dressing BC presents a unique reticulate network of thin fibres with application is cancer lesions, such as basal-cell carci- a diameter more than 100 times smaller than that of plant- noma or skin lesions related to chemotherapy and radia- derived fibres (Klemm et al., 2005). tion therapy. Larger lesions are usually vascularized and BC has many intrinsic characteristics that make it an necrotized, being responsible for high amounts of ideal scaffold for protecting injured tissues through drainage. wound dressings, especially for burn wounds, tissue For all these skin lesion conditions, the perfect wound regeneration and as temporary skin substitutes. Some dressing must maintain the moisture of the wound, allow of advantageous features of BC for these particular for oxygen exchange, adsorb wound exudate, accelerate applications are the fact that it is non-toxic, non-carci- re-epithelialization for wound closure, reduce pain and nogenic and biocompatible, and it has the capacity to healing time, and prevent infection. However, also addi- retain moisture, absorb exudates from the injured tis- tional and specific treatments adapted to the needs of sue and accelerate granulation (Li et al., 2015; Khalid each individual lesion are needed. All these require- et al., 2017). ments demand for a creative, integrative and flexible The largest organ in the human body is the skin. dressing application. Three layers, the epidermis, dermis and the fat layer, In health-related applications, natural-derived polymers also known as hypodermis, compose the skin. The epi- present several advantages when compared with syn- dermis is the external layer of the skin, having the critical thetic ones, such as biocompatibility, biodegradability and/ function of maintaining homeostasis of the body internal or biological activity, as most of them are present in the environment and at the same time protecting the body structural tissues of living organisms. Currently worldwide, from the external environment and from potential patho- burn wound and skin graft donor site treatments vary genic bacteria. The dermis is where all the blood ves- widely, and a large number of different wound dressing sels, nerves, hair follicles, oil and sweat glands are materials are available for their treatment (Voineskos located. In its native state, skin is dry and acidic in nat- et al., 2009). BC features, such as high porosity, high ure (pH between 4 and 6.8) being keratinocytes the skin water retention capacity, high mechanical strength in the cells responsible for producing skin lipids and to main- wet state, low density, biocompatibility, non-toxicity and tain hydration levels. Altered skin integrity may be due to biodegradability, make BC an outstanding material that is systemic factors, such as the nutritional status of the suitable for technological applications, particularly in the individual, vascular disease, heart conditions and dia- fields of biomedicine and pharmacology (Hu et al., 2014). betes, among others, or to extrinsic episodes such as BC has already been used quite successfully in accidents, immobility, pressure and surgical procedures. wound healing applications, proving that it could become When an individual suffers severe damage to large a high-value product in the field of biotechnology (Klemm areas of skin, such as burns, he is exposed to et al., 2001; Czaja et al., 2006). In fact, biomedical decreased local function, dehydration and infections that devices