Commercial and potential applications of bacterial cellulose in Brazil: ten years review

Luiz Diego Marestoni Hernane da Silva Barud Rodrigo José Gomes Rebeca Priscila Flora Catarino Natália Norika Yassunaka Hata Jéssica Barrionuevo Ressutte Wilma Aparecida Spinosa About the authors

Abstract

In the last decade, bacterial cellulose (BC) has received considerable attention around the world, including in Brazil. The unique properties of BC, such as mechanical stability, tensile strength, thermostability, crystallinity, purity and biocompatibility make it a promising candidate for commercial applications in different areas. This article provides a comprehensive synthesis of commercial applications and studies related to BC around the world and shows the importance and development of Brazilian research during the last decade. In this review we present an overview of BC structure, biosynthesis and possible applications of BC mainly in the food, electronics, bioengineering, cosmetics and biomedical areas. The most significant contributions of Brazilian researchers using BC have been carried out in the biomedical area. Despite the increase in BC reserch, Brazil also needs to develop strategies to expand the use and commercialization of BC products, for which government financial support is extremely necessary.

Keywords:
bacterial cellulose; bacterial cellulose applications; biomedical; Brazil; electronics

1. Introduction

During the last century, massive exploitation of fossil resources and pollution problems increased concerns related to the economy and the environment. In this context, polymers from renewable sources, like polysaccharides, among others, have received considerable and growing attention[11 Carreira, P., Mendes, J. A. S., Trovatti, E., Serafim, L. S., Freire, C. S. R., Silvestre, A. J. D., & Pascoal, C., No. (2011). Utilization of residues from agro-forest industries in the production of high value bacterial cellulose. Bioresource Technology, 102(15), 7354-7360. http://dx.doi.org/10.1016/j.biortech.2011.04.081. PMid:21601445.
http://dx.doi.org/10.1016/j.biortech.201...
]. Cellulose (C6H10O5)n is the most abundant renewable biopolymer produced in the biosphere, being basically composed of glucose monomers connected by β (1-4) glycosidic bonds. It can be synthesized by plants, animals and microorganisms[22 Castro, C., Zuluaga, R., Álvarez, C., Putaux, J. L., Caro, G., Rojas, O. J., Mondragon, I., & Gañán, P. (2012). Bacterial cellulose produced by a new acid-resistant strain of Gluconacetobacter genus. Carbohydrate Polymers, 89(4), 1033-1037. http://dx.doi.org/10.1016/j.carbpol.2012.03.045. PMid:24750910.
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,33 Qiu, X., & Hu, S. (2013). “Smart” materials based on cellulose: a review of the preparations, properties, and applications. Materials, 6(3), 738-781. http://dx.doi.org/10.3390/ma6030738. PMid:28809338.
http://dx.doi.org/10.3390/ma6030738...
].

Cellulose derived from plants is commonly incorporated into other biopolymers as hemicellulose and lignin; therefore, aggressive chemical treatments are necessary to remove these impurities[44 Sheykhnazari, S., Tabarsa, T., Ashori, A., Shakeri, A., & Golalipour, M. (2011). Bacterial synthesized cellulose nanofibers; Effects of growth times and culture mediums on the structural characteristics. Carbohydrate Polymers, 86(3), 1187-1191. http://dx.doi.org/10.1016/j.carbpol.2011.06.011.
http://dx.doi.org/10.1016/j.carbpol.2011...
]. On the other hand, BC produced by microbial fermentation is characterized by higher purity, and its purification is relatively simple, not requiring energy or chemically intensive processes. Furthermore, due its unique physical and chemical properties, BC has been successfully applied in the food, biomedicine, textile, and papermaking fields, as well as in biosorbent material and acoustic diaphragms[55 Chen, L., Hong, F., Yang, X., & Han, S. F. (2013). Biotransformation of wheat straw to bacterial cellulose and its mechanism. Bioresource Technology, 135, 464-468. http://dx.doi.org/10.1016/j.biortech.2012.10.029. PMid:23186663.
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,66 Dayal, M. S., Goswami, N., Sahai, A., Jain, V., Mathur, G., & Mathur, A. (2013). Effect of media components on cell growth and bacterial cellulose production from Acetobacter aceti MTCC 2623. Carbohydrate Polymers, 94(1), 12-16. http://dx.doi.org/10.1016/j.carbpol.2013.01.018. PMid:23544503.
http://dx.doi.org/10.1016/j.carbpol.2013...
].

However, the interest in cellulose is not only limited to industrial fields; it has also become increasingly relevant and interesting in academic areas[77 Kiziltas, E. E., Kiziltas, A., & Gardner, D. J. (2015). Synthesis of bacterial cellulose using hot water extracted wood sugars. Carbohydrate Polymers, 124, 131-138. http://dx.doi.org/10.1016/j.carbpol.2015.01.036. PMid:25839803.
http://dx.doi.org/10.1016/j.carbpol.2015...
]. Figure 1 shows an explosive increase in the number of publications related to BC since 2011. The years 2017, 2018, 2019 and 2020 have been the most productive in terms of publications. In Brazil, many groups have contributed and emerged in several areas of cellulose. In biomedicine, for example, Brazil was a pioneer, and gained prominence in employment of BC as an artificial skin to replace burned skin. Besides the commercial application in the biomedical area, potential applications of BC in Brazil include studies in the electronic/electrochemical/magnetic field, food and food packaging, cosmetic area, bioengineering, as well as in reinforcement material to make blends, composites and nanocomposites.

Figure 1
Evolution of the number of bacterial cellulose-related publications around the world, including Brazil, between 2011 and 2020. The searches were performed with Google scholar using the topics: bacterial cellulose, biocellulose, microbial cellulose and Brazil.

The aim of this review is to open with a sketch of the major cellulose-producing microorganisms and to provide a comprehensive discussion of cellulose synthesis. We then move to commercial applications of BC and the potential applications of biopolymers in Brazil and around the world by considering their uses ranging from food to medical industries.

1.1 Synthesis, properties and production of BC

The BC consists of a transparent and gelatinous pellicle, produced in the vast majority by the Gram-negative bacterial cultures of Acetobacter, Agrobacterium, Achromobacter, Aerobacter, Sarcina, Azotobacter, Rhizobium, Pseudomonas, Salmonella and Alcaligenes[88 Picheth, G. F., Pirich, C. L., Sierakowski, M. R., Woehl, M. A., Sakakibara, C. N., de Souza, C. F., Martin, A. A., da Silva, R., & de Freitas, R. A. (2017). Bacterial cellulose in biomedical applications: a review. International Journal of Biological Macromolecules, 104(Pt A), 97-106. http://dx.doi.org/10.1016/j.ijbiomac.2017.05.171. PMid:28587970.
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]. Among them, the most efficient BC producer belongs to the group of acetic acid bacteria (AAB) previously known as Acetobacter xylinum[99 Yamada, Y., & Yukphan, P. (2008). Genera and species in acetic acid bacteria. International Journal of Food Microbiology, 125(1), 15-24. http://dx.doi.org/10.1016/j.ijfoodmicro.2007.11.077. PMid:18199517.
http://dx.doi.org/10.1016/j.ijfoodmicro....
], which was recently transferred to the newly proposed genus Komagataeibacter and named Komagataeibacter xylinus[1010 Yamada, Y., Yukphan, P., Lan Vu, H. T., Muramatsu, Y., Ochaikul, D., Tanasupawat, S., & Nakagawa, Y. (2012). Description of Komagataeibacter gen. nov., with proposals of new combinations (Acetobacteraceae). The Journal of General and Applied Microbiology, 58(5), 397-404. http://dx.doi.org/10.2323/jgam.58.397. PMid:23149685.
http://dx.doi.org/10.2323/jgam.58.397...
].

It is suggested that cellulose production is a bacterial defense mechanism that can provide protection from hazardous ultraviolet light radiation effect and can help bacteria move to the aerobic environment of surface. Furthermore, the pellicule retains moisture and confers mechanical, chemical, and physiological protection[1111 Wang, S. S., Han, Y. H., Ye, Y. X., Shi, X. X., Xiang, P., Chen, D. L., & Li, M. (2017). Physicochemical characterization of high-quality bacterial cellulose produced by Komagataeibacter sp. strain W1 and identification of the associated genes in bacterial cellulose production. RSC Advances, 7(71), 45145-45155. http://dx.doi.org/10.1039/C7RA08391B.
http://dx.doi.org/10.1039/C7RA08391B...
,1212 Kumbhar, J. V., Rajwade, J. M., & Paknikar, K. M. (2015). Fruit peels support higher yield and superior quality bacterial cellulose production. Applied Microbiology and Biotechnology, 99(16), 6677-6691. http://dx.doi.org/10.1007/s00253-015-6644-8. PMid:25957154.
http://dx.doi.org/10.1007/s00253-015-664...
]. The biosynthesis of BC involves several biochemical processes containing a large number of enzymes, and the regulation of these key enzymes controls the cellulose production by means of three metabolic pathways: the pentose cycle, or branched hexose monophosphate pathway (HMP), for the oxidation of carbohydrates; the tricarboxylic acid cycle (TCA), for the oxidation of organic acids and other compounds; and the Embden-Meyerhof-Parnas pathway (EMP)[1313 Li, Y., Tian, C., Tian, H., Zhang, J., He, X., Ping, W., & Lei, H. (2012). Improvement of bacterial cellulose production by manipulating the metabolic pathways in which ethanol and sodium citrate involved. Applied Microbiology and Biotechnology, 96(6), 1479-1487. http://dx.doi.org/10.1007/s00253-012-4242-6. PMid:22782249.
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,1414 Ross, P., Mayer, R., & Benziman, A. N. D. M. (1991). Cellulose biosynthesis and function in bacteria. Microbiological Reviews, 55(1), 35-58. http://dx.doi.org/10.1128/MR.55.1.35-58.1991. PMid:2030672.
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].

Figure 2 briefly describes the biosynthetic pathway of K. xylinus cellulose production from glucose and fructose, although several other substrates can be used for this purpose[1717 Cacicedo, M. L., Castro, M. C., Servetas, I., Bosnea, L., Boura, K., Tsafrakidou, P., Dima, A., Terpou, A., Koutinas, A., & Castro, G. R. (2016). Progress in bacterial cellulose matrices for biotechnological applications. Bioresource Technology, 213, 172-180. http://dx.doi.org/10.1016/j.biortech.2016.02.071. PMid:26927233.
http://dx.doi.org/10.1016/j.biortech.201...
].

Figure 2
Pathway of cellulose synthesis from glucose and fructose in K. xylinus, also containing the direct path from Glucose-6-Phosphate to Glucose-1-Phosphate. GHK glucose hexokinase, FHK fructose hexokinase, 1PFK fructose-1-phosphate kinase, FBP fructose bisphosphatase, PGI phosphoglucose isomerase, PGM phosphoglucomutase, UGP UDP-glucose pyrophosphorylase, G6PD glucose-6-phosphate dehydrogenase, PTS phosphotransferase system; CS cellulose synthase; EMP Embden-Myerhoff pathway; HMP Hexose Monophosphate pathway[1313 Li, Y., Tian, C., Tian, H., Zhang, J., He, X., Ping, W., & Lei, H. (2012). Improvement of bacterial cellulose production by manipulating the metabolic pathways in which ethanol and sodium citrate involved. Applied Microbiology and Biotechnology, 96(6), 1479-1487. http://dx.doi.org/10.1007/s00253-012-4242-6. PMid:22782249.
http://dx.doi.org/10.1007/s00253-012-424...
,1515 Tonouch, N. (2016). Cellulose and other capsular polysaccharides of acetic acid bacteria. In K. Matsushita, H. Toyama, N. Tonouchi, & A. Okamoto-Kainuma (Eds.), Acetic acid bacteria (pp. 299-320). Tokyo: Springer.,1616 Lin, S. P., Loira Calvar, I., Catchmark, J. M., Liu, J. R., Demirci, A., & Cheng, K. C. (2013). Biosynthesis, production and applications of bacterial cellulose. Cellulose, 20(5), 2191-2219. http://dx.doi.org/10.1007/s10570-013-9994-3.
http://dx.doi.org/10.1007/s10570-013-999...
].

Cellulose synthesis from glucose occurs initially through phosphorylation of hexose by GHK, thereby producing Glucose-6-Phosphate (G6P). G6P is metabolized by the Hexose monophosphate pathway, since Fructose-6-phosphate cannot be converted to Fructose-1,6-phosphate. Next, G6P is metabolized to UDP-glucose (UDPG), a direct precursor of the biopolymer, by PGM and UGP enzymatic action[1515 Tonouch, N. (2016). Cellulose and other capsular polysaccharides of acetic acid bacteria. In K. Matsushita, H. Toyama, N. Tonouchi, & A. Okamoto-Kainuma (Eds.), Acetic acid bacteria (pp. 299-320). Tokyo: Springer.]. The fructose can be metabolized to cellulose following two paths: (I) phosphorylation of fructose to Fructose-6-phosphate (F6P) by FHK, and (II) phosphorylation of fructose to Fructose-1-phosphate (F1P) by PTS. In the first, PGI changes F6P to G6P, which can be used for cellulose production or can proceed to the Hexose monophosphate pathway. In (II) 1PFK transforms PF1 into Fructose-1,6-diphosphate (FDP) and it is later dephosphorylated to F6P. Through the EMP, FDP can also be metabolized, starting the whole process of cellulose synthesis[1818 Tonouchi, N., Tsuchida, T., Yoshinaga, F., Beppu, T., & Horinouchi, S. (1996). Characterization of the biosynthetic pathway of cellulose from glucose and fructose in Acetobacter xylinum. Bioscience, Biotechnology, and Biochemistry, 60(8), 1377-1379. http://dx.doi.org/10.1271/bbb.60.1377.
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].

Microscopic analysis has shown that from one bacterial cell a single cellulose ribbon is produced (Figure 3). The single ribbon is constituted of a structure of cellulose microfibrils that are excreted from a row of a complex of proteins called the terminal complexes (TCs), located in the outer cell membrane[1919 Koizumi, S., Yue, Z., Tomita, Y., Kondo, T., Iwase, H., Yamaguchi, D., & Hashimoto, T. (2008). Bacterium organizes hierarchical amorphous structure in microbial cellulose. The European Physical Journal E, 26(1-2), 137-142. http://dx.doi.org/10.1140/epje/i2007-10259-3. PMid:18311475.
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,2020 Kimura, S., Chen, H. P., Saxena, I. M., Brown, J., Jr., & Itoh, T. (2001). Localization of c-di-GMP-binding protein with the linear terminal complexes of Acetobacter xylinum. Journal of Bacteriology, 183(19), 5668-5674. http://dx.doi.org/10.1128/JB.183.19.5668-5674.2001. PMid:11544230.
http://dx.doi.org/10.1128/JB.183.19.5668...
]. During the conversion of glucose to UDPG in cytoplasm, a row of 60 TCs conducts the recognition and synthesis of UDPG, as well as the crystallization and extrusion of cellulose fibers[1919 Koizumi, S., Yue, Z., Tomita, Y., Kondo, T., Iwase, H., Yamaguchi, D., & Hashimoto, T. (2008). Bacterium organizes hierarchical amorphous structure in microbial cellulose. The European Physical Journal E, 26(1-2), 137-142. http://dx.doi.org/10.1140/epje/i2007-10259-3. PMid:18311475.
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].

Figure 3
Schematic diagram of microbial cellulose organization. Adapted from Picheth et al.[88 Picheth, G. F., Pirich, C. L., Sierakowski, M. R., Woehl, M. A., Sakakibara, C. N., de Souza, C. F., Martin, A. A., da Silva, R., & de Freitas, R. A. (2017). Bacterial cellulose in biomedical applications: a review. International Journal of Biological Macromolecules, 104(Pt A), 97-106. http://dx.doi.org/10.1016/j.ijbiomac.2017.05.171. PMid:28587970.
http://dx.doi.org/10.1016/j.ijbiomac.201...
] and Koizumi et al.[1919 Koizumi, S., Yue, Z., Tomita, Y., Kondo, T., Iwase, H., Yamaguchi, D., & Hashimoto, T. (2008). Bacterium organizes hierarchical amorphous structure in microbial cellulose. The European Physical Journal E, 26(1-2), 137-142. http://dx.doi.org/10.1140/epje/i2007-10259-3. PMid:18311475.
http://dx.doi.org/10.1140/epje/i2007-102...
].

Komagataeibacter species are able to produce two forms of cellulose: (I) cellulose I, the ribbon-like polymer; and (II) cellulose II, which is the most thermodynamically stable amorphous form of the polymer. While cellulose I is constituted of parallel β (1-4) glucan chains organized uniaxially with van der Waals forces, β (1-4) glucan chains of cellulose II are arranged in random way. The latter is mainly antiparallel, with a large number of hydrogen bonds that provide more stability to the structure[2121 Mohite, B. V., & Patil, S. V. (2014). Physical, structural, mechanical and thermal characterization of bacterial cellulose by G. hansenii NCIM 2529. Carbohydrate Polymers, 106(1), 132-141. http://dx.doi.org/10.1016/j.carbpol.2014.02.012. PMid:24721060.
http://dx.doi.org/10.1016/j.carbpol.2014...
]. According to Koizumi et al.[1919 Koizumi, S., Yue, Z., Tomita, Y., Kondo, T., Iwase, H., Yamaguchi, D., & Hashimoto, T. (2008). Bacterium organizes hierarchical amorphous structure in microbial cellulose. The European Physical Journal E, 26(1-2), 137-142. http://dx.doi.org/10.1140/epje/i2007-10259-3. PMid:18311475.
http://dx.doi.org/10.1140/epje/i2007-102...
], during the BC synthesis, the amorphous regions, interspersed among crystalline regions, occupy 90% of material total volume.

Due to its microfibrillar structure, several mechanical properties are attributed to BC, such as: tensile strength, which may vary between 200-300 MPa with Young’s modulus, up to 15-35 GPa; and thermal stability, reaching temperatures above 100 °C without changes in their biophysical properties[1717 Cacicedo, M. L., Castro, M. C., Servetas, I., Bosnea, L., Boura, K., Tsafrakidou, P., Dima, A., Terpou, A., Koutinas, A., & Castro, G. R. (2016). Progress in bacterial cellulose matrices for biotechnological applications. Bioresource Technology, 213, 172-180. http://dx.doi.org/10.1016/j.biortech.2016.02.071. PMid:26927233.
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,2222 Ruka, D. R., Simon, G. P., & Dean, K. M. (2014). Bacterial cellulose and its use in renewable composites. In V. J. Thakur (Ed.), Nanocellulose polymer nanocomposites: fundamentals and applications (pp. 89-130). Salem: Wiley. http://dx.doi.org/10.1002/9781118872246.ch4.
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,2323 Qiu, K., & Netravali, A. N. (2014). A review of fabrication and applications of bacterial cellulose based nanocomposites. Polymer Reviews, 54(4), 598-626. http://dx.doi.org/10.1080/15583724.2014.896018.
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]. Furthermore, BC presents high purity, high degree of polymerization, water holding capacity up to a hundred times its weight, excellent biodegradability and biological affinity and non-allergenicity[1111 Wang, S. S., Han, Y. H., Ye, Y. X., Shi, X. X., Xiang, P., Chen, D. L., & Li, M. (2017). Physicochemical characterization of high-quality bacterial cellulose produced by Komagataeibacter sp. strain W1 and identification of the associated genes in bacterial cellulose production. RSC Advances, 7(71), 45145-45155. http://dx.doi.org/10.1039/C7RA08391B.
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,2424 Shoda, M., & Sugano, Y. (2005). Recent advances in bacterial cellulose production. Biotechnology and Bioprocess Engineering; BBE, 10(1), 1-8. http://dx.doi.org/10.1007/BF02931175.
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25 Huang, Y., Zhu, C., Yang, J., Nie, Y., Chen, C., & Sun, D. (2014). Recent advances in bacterial cellulose. Cellulose, 21(1), 1-30. http://dx.doi.org/10.1007/s10570-013-0088-z.
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26 Fan, X., Gao, Y., He, W., Hu, H., Tian, M., Wang, K., & Pan, S. (2016). Production of nano bacterial cellulose from beverage industrial waste of citrus peel and pomace using Komagataeibacter xylinus. Carbohydrate Polymers, 151, 1068-1072. http://dx.doi.org/10.1016/j.carbpol.2016.06.062. PMid:27474656.
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-2727 Keshk, S. M. (2014). Bacterial cellulose production and its industrial applications. Journal of Bioprocessing & Biotechniques, 4(2), 1-10. http://dx.doi.org/10.4172/2155-9821.1000150.
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]. The structure, physical, and mechanical properties of BC are directly related to the cultivation technique employed, of which, the main methods of production are static, agitating culture, and the airlift reactor [1616 Lin, S. P., Loira Calvar, I., Catchmark, J. M., Liu, J. R., Demirci, A., & Cheng, K. C. (2013). Biosynthesis, production and applications of bacterial cellulose. Cellulose, 20(5), 2191-2219. http://dx.doi.org/10.1007/s10570-013-9994-3.
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].

Despite its unique properties, the production of BC is still limited due to difficulties in the large-scale production, which are related to long-time cultivation methods, low production yields, bacterial strain mutation and high cost of the process. The static method is the simplest and widely used to produce BC, mainly in lab-scale[2929 Wang, J., Tavakoli, J., & Tang, Y. (2019). Bacterial cellulose production, properties and applications with different culture methods: a review. Carbohydrate Polymers, 219, 63-76. http://dx.doi.org/10.1016/j.carbpol.2019.05.008. PMid:31151547.
http://dx.doi.org/10.1016/j.carbpol.2019...
]. This technique presents high cost, long cultivation time (~7-20 days), low productivity, and uneven distribution of nutrients, oxygen and cells, resulting in a material with non-uniform thickness[3030 Blanco Parte, F. G., Santoso, S. P., Chou, C. C., Verma, V., Wang, H. T., Ismadji, S., & Cheng, K. C. (2020). Current progress on the production, modification, and applications of bacterial cellulose. Critical Reviews in Biotechnology, 40(3), 397-414. http://dx.doi.org/10.1080/07388551.2020.1713721. PMid:31937141.
http://dx.doi.org/10.1080/07388551.2020....
]. On the other hand, the agitation method favors the diffusion of oxygen and the availability of nutrients, promoting greater production and shorter cultivation time (~5 days). However, it is associated with mutation and formation of non-cellulose-forming cells[3131 Islam, M. U., Ullah, M. W., Khan, S., Shah, N., & Park, J. K. (2017). Strategies for cost-effective and enhanced production of bacterial cellulose. International Journal of Biological Macromolecules, 102, 1166-1173. http://dx.doi.org/10.1016/j.ijbiomac.2017.04.110. PMid:28487196.
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,3232 Singhsa, P., Narain, R., & Manuspiya, H. (2018). Physical structure variations of bacterial cellulose produced by different Komagataeibacter xylinus strains and carbon sources in static and agitated conditions. Cellulose, 25(3), 1571-1581. http://dx.doi.org/10.1007/s10570-018-1699-1.
http://dx.doi.org/10.1007/s10570-018-169...
].

Studies have also been conducted to find strains with high capacity for BC synthesis, besides employing genetic engineering techniques to improve the production[3333 He, X., Meng, H., Song, H., Deng, S., He, T., Wang, S., Wei, D., & Zhang, Z. (2020). Novel bacterial cellulose membrane biosynthesized by a new and highly efficient producer Komagataeibacter rhaeticus TJPU03. Carbohydrate Research, 493, 108030. http://dx.doi.org/10.1016/j.carres.2020.108030. PMid:32442702.
http://dx.doi.org/10.1016/j.carres.2020....

34 Lu, T., Gao, H., Liao, B., Wu, J., Zhang, W., Huang, J., Liu, M., Huang, J., Chang, Z., Jin, M., Yi, Z., & Jiang, D. (2020). Characterization and optimization of production of bacterial cellulose from strain CGMCC 17276 based on whole-genome analysis. Carbohydrate Polymers, 232, 115788. http://dx.doi.org/10.1016/j.carbpol.2019.115788. PMid:31952596.
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-3535 Revin, V. V., Liyas’kina, E. V., Sapunova, N. B., & Bogatyreva, A. O. (2020). Isolation and characterization of the strains producing bacterial cellulose. Microbiology, 89(1), 86-95. http://dx.doi.org/10.1134/S0026261720010130.
http://dx.doi.org/10.1134/S0026261720010...
]. Alternatively, bioreactors can be employed for industrial-scale production of BC, since they show higher yield compared to static and agitated methods. Some bioreactors developed use oxygen, rotating disc and can produce BC through biofilm support. This method still requires studies that allow the use of controlled parameters and low-cost substrates[2929 Wang, J., Tavakoli, J., & Tang, Y. (2019). Bacterial cellulose production, properties and applications with different culture methods: a review. Carbohydrate Polymers, 219, 63-76. http://dx.doi.org/10.1016/j.carbpol.2019.05.008. PMid:31151547.
http://dx.doi.org/10.1016/j.carbpol.2019...
,3636 Sharma, C., & Bhardwaj, N. K. (2019). Bacterial nanocellulose: present status, biomedical applications and future perspectives. Materials Science and Engineering C, 104, 109963. http://dx.doi.org/10.1016/j.msec.2019.109963. PMid:31499992.
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].

To find new cost-effective fermentation media to replace the expensive Hestrin-Schramm medium (standard medium), researchers have checked the use of media containing either sugary materials or even agricultural and industrial waste products[3737 Chandrasekaran, P. T., Bari, N. K., & Sinha, S. (2017). Enhanced bacterial cellulose production from Gluconobacter xylinus using super optimal broth. Cellulose, 24(10), 4367-4381. http://dx.doi.org/10.1007/s10570-017-1419-2.
http://dx.doi.org/10.1007/s10570-017-141...
]. In such media containing high sugar content, are included the fruit juices[3838 Kurosumi, A., Sasaki, C., Yamashita, Y., & Nakamura, Y. (2009). Utilization of various fruit juices as carbon source for production of bacterial cellulose by Acetobacter xylinum NBRC 13693. Carbohydrate Polymers, 76(2), 333-335. http://dx.doi.org/10.1016/j.carbpol.2008.11.009.
http://dx.doi.org/10.1016/j.carbpol.2008...
] and related by-products such as fruit peels[1212 Kumbhar, J. V., Rajwade, J. M., & Paknikar, K. M. (2015). Fruit peels support higher yield and superior quality bacterial cellulose production. Applied Microbiology and Biotechnology, 99(16), 6677-6691. http://dx.doi.org/10.1007/s00253-015-6644-8. PMid:25957154.
http://dx.doi.org/10.1007/s00253-015-664...
,3939 Güzel, M., & Akpınar, Ö. (2019). Production and characterization of bacterial cellulose from citrus peels. Waste and Biomass Valorization, 10(8), 2165-2175. http://dx.doi.org/10.1007/s12649-018-0241-x.
http://dx.doi.org/10.1007/s12649-018-024...
] and rotten fruit[4040 Jozala, A. F., Pértile, R. A. N., Santos, C. A., Santos-Ebinuma, V. C., Seckler, M. M., Gama, F. M., & Pessoa, A., Jr. (2015). Bacterial cellulose production by Gluconacetobacter xylinus by employing alternative culture media. Applied Microbiology and Biotechnology, 99(3), 1181-1190. http://dx.doi.org/10.1007/s00253-014-6232-3. PMid:25472434.
http://dx.doi.org/10.1007/s00253-014-623...
]. Molasses derived from the industries of sugarcane[4141 Machado, R. T. A., Meneguin, A. B., Sábio, R. M., Franco, D. F., Antonio, S. G., Gutierrez, J., Tercjak, A., Berretta, A. A., Ribeiro, S. J. L., Lazarini, S. C., Lustri, W. R., & Barud, H. S. (2018). Komagataeibacter rhaeticus grown in sugarcane molasses-supplemented culture medium as a strategy for enhancing bacterial cellulose production. Industrial Crops and Products, 122, 637-646. http://dx.doi.org/10.1016/j.indcrop.2018.06.048.
http://dx.doi.org/10.1016/j.indcrop.2018...
], beet[4242 Salari, M., Sowti Khiabani, M., Rezaei Mokarram, R., Ghanbarzadeh, B., & Samadi Kafil, H. (2019). Preparation and characterization of cellulose nanocrystals from bacterial cellulose produced in sugar beet molasses and cheese whey media. International Journal of Biological Macromolecules, 122, 280-288. http://dx.doi.org/10.1016/j.ijbiomac.2018.10.136. PMid:30342939.
http://dx.doi.org/10.1016/j.ijbiomac.201...
] and soybean[4343 Souza, E. F., Furtado, M. R., Carvalho, C. W. P., Freitas-Silva, O., & Gottschalk, L. M. F. (2020). Production and characterization of Gluconacetobacter xylinus bacterial cellulose using cashew apple juice and soybean molasses. International Journal of Biological Macromolecules, 146, 285-289. http://dx.doi.org/10.1016/j.ijbiomac.2019.12.180. PMid:31883899.
http://dx.doi.org/10.1016/j.ijbiomac.201...
] have also been tested for production. Other several agricultural and industrial residues already tested include waste beer yeasts, fruit bagasse, cheese whey, glycerol and textile wastes[4444 Hussain, Z., Sajjad, W., Khan, T., & Wahid, F. (2019). Production of bacterial cellulose from industrial wastes: a review. Cellulose, 26(5), 2895-2911. http://dx.doi.org/10.1007/s10570-019-02307-1.
http://dx.doi.org/10.1007/s10570-019-023...
]. These industrial by-products, rich in sugars and other nutrients could be suitable fermentative substrates for the production of BC, since they have low-cost and good sources of carbon[4545 Velásquez-Riaño, M., & Bojacá, V. (2017). Production of bacterial cellulose from alternative low-cost substrates. Cellulose, 24(7), 2677-2698. http://dx.doi.org/10.1007/s10570-017-1309-7.
http://dx.doi.org/10.1007/s10570-017-130...
]. By using these strategies, it is possible not only to make the BC production more economically feasible, but also make it more ecologically sustainable, which could help to reduce the release of waste by industries. Other strategies include screening of high-yield strains, inhibition of mutation, controlled side product formation, selection of suitable cultivation methods, optimization of medium composition, and searching for low-cost raw materials[3131 Islam, M. U., Ullah, M. W., Khan, S., Shah, N., & Park, J. K. (2017). Strategies for cost-effective and enhanced production of bacterial cellulose. International Journal of Biological Macromolecules, 102, 1166-1173. http://dx.doi.org/10.1016/j.ijbiomac.2017.04.110. PMid:28487196.
http://dx.doi.org/10.1016/j.ijbiomac.201...
].

1.2 Overview of commercial applications of BC

Considering all the properties of BC, it is expected that this polymer will have several industrial applications. In fact, the number of patent applications registered around the world has been quite impressive, but unfortunately, few commercial applications have been pursued[1515 Tonouch, N. (2016). Cellulose and other capsular polysaccharides of acetic acid bacteria. In K. Matsushita, H. Toyama, N. Tonouchi, & A. Okamoto-Kainuma (Eds.), Acetic acid bacteria (pp. 299-320). Tokyo: Springer.].

Among the most known industrial applications of BC is the “nata de coco”, a traditional food consumed in the Philippines and other countries in Southeast Asia. The manufacturing process of this jelly-like product consists of using coconut water as a fermentation medium for cellulose production. The pellicule is then cleaned, washed, chopped and immersed in sugar syrup, to be served as a dessert. Originally from Southeast Asia, nata de coco became a very popular food worldwide[1515 Tonouch, N. (2016). Cellulose and other capsular polysaccharides of acetic acid bacteria. In K. Matsushita, H. Toyama, N. Tonouchi, & A. Okamoto-Kainuma (Eds.), Acetic acid bacteria (pp. 299-320). Tokyo: Springer.,4646 Iguchi, M., Yamanaka, S., & Budhiono, A. (2000). Bacterial cellulose: a masterpiece of nature’s arts. Journal of Materials Science, 35(2), 261-270. http://dx.doi.org/10.1023/A:1004775229149.
http://dx.doi.org/10.1023/A:100477522914...
,4747 Ullah, H., Santos, H. A., & Khan, T. (2016). Applications of bacterial cellulose in food, cosmetics and drug delivery. Cellulose, 23(4), 2291-2314. http://dx.doi.org/10.1007/s10570-016-0986-y.
http://dx.doi.org/10.1007/s10570-016-098...
]. Japan and the USA are the largest markets for nata de coco; between 2009 and 2011, the export volume from the Philippines reached an average of 6000 MT (Metric Tons)[4848 Dourado, F., Gama, M., & Rodrigues, A. C. (2017). A Review on the toxicology and dietetic role of bacterial cellulose. Toxicology Reports, 4, 543-553. http://dx.doi.org/10.1016/j.toxrep.2017.09.005. PMid:29090119.
http://dx.doi.org/10.1016/j.toxrep.2017....
].

Potential application of BC has also been reported in the acoustic transducers area; BC presents remarkable shape retention ability, measured as the Young’s Modulus, and also bears two essential properties for speaker diaphragms: high sonic velocity and low dynamics loss. Thus, novel diaphragms have been marketed by Sony Corp. as headphones[1616 Lin, S. P., Loira Calvar, I., Catchmark, J. M., Liu, J. R., Demirci, A., & Cheng, K. C. (2013). Biosynthesis, production and applications of bacterial cellulose. Cellulose, 20(5), 2191-2219. http://dx.doi.org/10.1007/s10570-013-9994-3.
http://dx.doi.org/10.1007/s10570-013-999...
,4646 Iguchi, M., Yamanaka, S., & Budhiono, A. (2000). Bacterial cellulose: a masterpiece of nature’s arts. Journal of Materials Science, 35(2), 261-270. http://dx.doi.org/10.1023/A:1004775229149.
http://dx.doi.org/10.1023/A:100477522914...
].

Regarding applicability of BC in biomedicine, Brazil participated in one of the main applications associated with wound dressing, in which Fontana et al.[4949 Fontana, J. D., Souza, A. M., Fontana, C. K., Torriani, I. L., Moreschi, J. C., Gallotti, B. J., de Souza, S. J., Narcisco, G. P., Bichara, J. A., & Farah, L. F. (1990). Acetobacter cellulose pellicle as a temporary skin substitute. Applied Biochemistry and Biotechnology, 24-25(1), 253-264. http://dx.doi.org/10.1007/BF02920250. PMid:2353811.
http://dx.doi.org/10.1007/BF02920250...
] became pioneers in employing BC as an artificial skin to replace burned skin. BioFill® and Bioprocess® (BioFill Produtos Biotecnológicos – Curitiba, PR, Brazil; used as temporary skin in the treatment of burns and ulcers) and Gengiflex (BioFill Produtos Biotecnológicos; applied in periodontal diseases) are examples of Brazilian commercial products of BC-based wound healing systems that have been launched. Although these launches are no longer on the market, other products as NEXFILL, DERMAFILL and CUTICELL EPIGRAFT (Seven Indústria de Produtos Biotecnológicos Ltda – Londrina, PR, Brazil), Biocel (DMC Importação e Exportação de Equipamentos LTDA - São Carlos, SP, Brazil; Florida USA), Bionext® (Bionext® Produtos Biotecnológicos Ltda – São Paulo, Brazil), and Membracel® (Vuelo Pharma – Curitiba, PR, Brazil), emerged, thereby demonstrating the relevance of BC application in this area. Among other products available around the world are CelMat® Wound (BOWIL Biotech sp. - Poland), Bio-skinG (Coreleader Biotech Co. Ltd. - New Taipei City Taiwan) and XCell (Xylos Corporation – US; used to maintain an ideal moisture balance). The prerequisites for BC to be applied as a wound dressing include: high mechanical strength in a wet state, water vapor permeability, good adherence to the wound, low cost, good biocompatibility, durability, transparence and easy handling[1515 Tonouch, N. (2016). Cellulose and other capsular polysaccharides of acetic acid bacteria. In K. Matsushita, H. Toyama, N. Tonouchi, & A. Okamoto-Kainuma (Eds.), Acetic acid bacteria (pp. 299-320). Tokyo: Springer.,1616 Lin, S. P., Loira Calvar, I., Catchmark, J. M., Liu, J. R., Demirci, A., & Cheng, K. C. (2013). Biosynthesis, production and applications of bacterial cellulose. Cellulose, 20(5), 2191-2219. http://dx.doi.org/10.1007/s10570-013-9994-3.
http://dx.doi.org/10.1007/s10570-013-999...
,5050 Oliveira Barud, H. G., Silva, R. R., Silva Barud, H., Tercjak, A., Gutierrez, J., Lustri, W. R., Oliveira, O. B., & Ribeiro, S. J. L. (2016). A multipurpose natural and renewable polymer in medical applications: bacterial cellulose. Carbohydrate Polymers, 153, 406-420. http://dx.doi.org/10.1016/j.carbpol.2016.07.059. PMid:27561512.
http://dx.doi.org/10.1016/j.carbpol.2016...
].

The increase in cardiovascular diseases has also led the researchers to reflect about the need for replacement blood vessels[5151 Picheth, G. F., Sierakowski, M. R., Woehl, M. A., Ono, L., Cofré, A. R., Vanin, L. P., Pontarolo, R., & De Freitas, R. A. (2014). Lysozyme-triggered epidermal growth factor release from bacterial cellulose membranes controlled by smart nanostructured films. Journal of Pharmaceutical Sciences, 103(12), 3958-3965. http://dx.doi.org/10.1002/jps.24205. PMid:25308839.
http://dx.doi.org/10.1002/jps.24205...
]. Klemm et al.[5252 Klemm, D., Schumann, D., Udhardt, U., & Marsch, S. (2001). Bacterial synthesized cellulose: artificial blood vessels for microsurgery. Progress in Polymer Science, 26(9), 1561-1603. http://dx.doi.org/10.1016/S0079-6700(01)00021-1.
http://dx.doi.org/10.1016/S0079-6700(01)...
] have developed a clinical product from BC and patented it as BASYC®-tubes (BActerial SYnthesized Cellulose). Besides their suitability for different inner diameter vascular conduits, studies show BASYC tubes have high mechanical strength in a wet state, great water retention properties and can be successfully used to replace carotid arteries in rats, pigs and sheep[5050 Oliveira Barud, H. G., Silva, R. R., Silva Barud, H., Tercjak, A., Gutierrez, J., Lustri, W. R., Oliveira, O. B., & Ribeiro, S. J. L. (2016). A multipurpose natural and renewable polymer in medical applications: bacterial cellulose. Carbohydrate Polymers, 153, 406-420. http://dx.doi.org/10.1016/j.carbpol.2016.07.059. PMid:27561512.
http://dx.doi.org/10.1016/j.carbpol.2016...
,5353 Lin, N., & Dufresne, A. (2014). Nanocellulose in biomedicine: current status and future prospect. European Polymer Journal, 59, 302-325. http://dx.doi.org/10.1016/j.eurpolymj.2014.07.025.
http://dx.doi.org/10.1016/j.eurpolymj.20...
].

1.3 Reports applications of BC around the world and in Brazil

The studies related to the potential applications of BC in Brazil, as on the world stage, involve the biomedical area, electronic/electrochemical/magnetic field, food and food packaging, bioengineering and the cosmetics area (Figure 4 and 5). The studies also involve the use of reinforcement material to make blends, composites and nanocomposites, with possible application in many fields. For such applications, the properties of BC have usually been tailored by using various in situ techniques (such as addition of various substances and alteration of culture conditions) and ex situ strategies (physical and chemical modification)[5454 Cazón, P., & Vázquez, M. (2021). Improving bacterial cellulose films by ex-situ and in-situ modifications: a review. Food Hydrocolloids, 113, 106514. http://dx.doi.org/10.1016/j.foodhyd.2020.106514.
http://dx.doi.org/10.1016/j.foodhyd.2020...
,5555 Gorgieva, S., & Trček, J. (2019). Bacterial cellulose: production, modification and perspectives in biomedical applications. Nanomaterials, 9(10), 1352. http://dx.doi.org/10.3390/nano9101352. PMid:31547134.
http://dx.doi.org/10.3390/nano9101352...
]. These applications are discussed in detail in the following sections.

Figure 4
Main applications of bacterial cellulose in the world.
Figure 5
Main applications of bacterial cellulose in Brazil.

1.3.1 Food and food packaging

1.3.1.1 World

Considered a dietary fiber and classified as “generally recognized as safe” (GRAS) by the USA Food and Drug Administration in 1992, BC can offer several health benefits, reducing the risk of chronic diseases such as cardiovascular disease, diabetes, obesity and diverticulitis[1717 Cacicedo, M. L., Castro, M. C., Servetas, I., Bosnea, L., Boura, K., Tsafrakidou, P., Dima, A., Terpou, A., Koutinas, A., & Castro, G. R. (2016). Progress in bacterial cellulose matrices for biotechnological applications. Bioresource Technology, 213, 172-180. http://dx.doi.org/10.1016/j.biortech.2016.02.071. PMid:26927233.
http://dx.doi.org/10.1016/j.biortech.201...
,4747 Ullah, H., Santos, H. A., & Khan, T. (2016). Applications of bacterial cellulose in food, cosmetics and drug delivery. Cellulose, 23(4), 2291-2314. http://dx.doi.org/10.1007/s10570-016-0986-y.
http://dx.doi.org/10.1007/s10570-016-098...
]. Most of the approaches use BC as a raw material for obtaining new products and explore its use as food additive.

In this area, BC has been used as a fat substitute; as potential gelling, thickening, suspending and emulsion stabilizer, as solid support to immobilize cells and as food packaging. As a fat substitute, reports are found in the literature of BC application in meatballs[5656 Lin, K. W., & Lin, H. Y. (2004). Quality characteristics of chinese-style meatball containing bacterial cellulose (nata). Journal of Food Science, 69(3), SNQ107-SNQ111. http://dx.doi.org/10.1111/j.1365-2621.2004.tb13378.x.
http://dx.doi.org/10.1111/j.1365-2621.20...
], surimi products[5757 Lin, S., Chen, L.-C., & Chen, H.-H. (2011). Physical characteristics of surimi and bacterial cellulose composite gel. Journal of Food Process Engineering, 34(4), 1363-1379. http://dx.doi.org/10.1111/j.1745-4530.2009.00533.x.
http://dx.doi.org/10.1111/j.1745-4530.20...
], cheese[5858 Karahan, A. G., Kart, A., Akoǧlu, A., & Çakmakçi, M. L. (2011). Physicochemical properties of low-fat soft cheese Turkish Beyaz made with bacterial cellulose as fat mimetic. International Journal of Dairy Technology, 64(4), 502-508. http://dx.doi.org/10.1111/j.1471-0307.2011.00718.x.
http://dx.doi.org/10.1111/j.1471-0307.20...
], ice cream[5959 Guo, Y., Zhang, X., Hao, W., Xie, Y., Chen, L., Li, Z., Zhu, B., & Feng, X. (2018). Nano-bacterial cellulose/soy protein isolate complex gel as fat substitutes in ice cream model. Carbohydrate Polymers, 198, 620-630. http://dx.doi.org/10.1016/j.carbpol.2018.06.078. PMid:30093042.
http://dx.doi.org/10.1016/j.carbpol.2018...
] and mayonnaise[6060 Akoğlu, A., Cakir, I., Karahan, A. G., & Cakmakci, M. L. (2018). Effects of bacterial cellulose as a fat replacer on some properties of fat-reduced mayonnaise. Romanian Biotechnological Letters, 23(3), 13674-13680.]. BC also has been applied as a potential gelling, thickening, suspending and emulsion stabilizer to produce meat products[6161 Marchetti, L., Muzzio, B., Cerrutti, P., Andrés, S. C., & Califano, A. N. (2017). Impact of bacterial nanocellulose on the rheological and textural characteristics of low-lipid meat emulsions. In A. E. Oprea & A. M. Grumezescu (Eds.), Nanotechnology applications in food (pp. 345-361). Amsterdam: Elsevier. http://dx.doi.org/10.1016/B978-0-12-811942-6.00017-0.
http://dx.doi.org/10.1016/B978-0-12-8119...
], whey protein isolate[6262 Paximada, P., Koutinas, A. A., Scholten, E., & Mandala, I. G. (2016). Effect of bacterial cellulose addition on physical properties of WPI emulsions: comparison with common thickeners. Food Hydrocolloids, 54, 245-254. http://dx.doi.org/10.1016/j.foodhyd.2015.10.014.
http://dx.doi.org/10.1016/j.foodhyd.2015...
], olive oil[6363 Yan, H., Chen, X., Song, H., Li, J., Feng, Y., Shi, Z., Wang, X., & Lin, Q. (2017). Synthesis of bacterial cellulose and bacterial cellulose nanocrystals for their applications in the stabilization of olive oil pickering emulsion. Food Hydrocolloids, 72, 127-135. http://dx.doi.org/10.1016/j.foodhyd.2017.05.044.
http://dx.doi.org/10.1016/j.foodhyd.2017...
] and edible foam[6464 Zhang, X., Zhou, J., Chen, J., Li, B., Li, Y., & Liu, S. (2020). Edible foam based on pickering effect of bacterial cellulose nanofibrils and soy protein isolates featuring interfacial network stabilization. Food Hydrocolloids, 100, 105440. http://dx.doi.org/10.1016/j.foodhyd.2019.105440.
http://dx.doi.org/10.1016/j.foodhyd.2019...
].

Recently, BC has gained prominence in studies related to the immobilization processes of cells, enzymes and probiotics for application in food[6565 Fijałkowski, K., Peitler, D., Rakoczy, R., & Zywicka, A. (2016). Survival of probiotic lactic acid bacteria immobilized in different forms of bacterial cellulose in simulated gastric juices and bile salt solution. Lebensmittel-Wissenschaft + Technologie, 68, 322-328. http://dx.doi.org/10.1016/j.lwt.2015.12.038.
http://dx.doi.org/10.1016/j.lwt.2015.12....
]. Some authors immobilize yeast in BC for wine production. Immobilized yeast reduced expenses for inoculum preparation, since the yeast was recovered and separated at the end of the fermentation process[6666 Nguyen, D. N., Ton, N. M. N., & Le, V. V. M. (2009). Optimization of Saccharomyces cerevisiae immobilization in bacterial cellulose by ‘adsorption- incubation ’ method. International Food Research Journal, 64, 59-64.]. Similarly, Fijałkowski et al.[6565 Fijałkowski, K., Peitler, D., Rakoczy, R., & Zywicka, A. (2016). Survival of probiotic lactic acid bacteria immobilized in different forms of bacterial cellulose in simulated gastric juices and bile salt solution. Lebensmittel-Wissenschaft + Technologie, 68, 322-328. http://dx.doi.org/10.1016/j.lwt.2015.12.038.
http://dx.doi.org/10.1016/j.lwt.2015.12....
] obtained promising results in immobilizing probiotic strains of Lactobacillus spp in BC.

In the literature, the most explored food area worldwide is the development of films and packaging. BC has been incorporated into a wide variety of substances in order to increase the shelf life of food products[6767 Gedarawatte, S. T. G., Ravensdale, J. T., Johns, M. L., Azizi, A., Al-Salami, H., Dykes, G. A., & Coorey, R. (2020). Effectiveness of bacterial cellulose in controlling purge accumulation and improving physicochemical, microbiological, and sensorial properties of vacuum-packaged beef. Journal of Food Science, 85(7), 2153-2163. http://dx.doi.org/10.1111/1750-3841.15178. PMid:32572986.
http://dx.doi.org/10.1111/1750-3841.1517...
]. Among the substances to which BC has been incorporated for the production of packaging can be mentioned: cotton fibers[6868 Ma, X., Chen, Y., Huang, J., Lv, P., Hussain, T., & Wei, Q. (2020). In situ formed active and intelligent bacterial cellulose/cotton fiber composite containing curcumin. Cellulose, 27(16), 9371-9382. http://dx.doi.org/10.1007/s10570-020-03413-1.
http://dx.doi.org/10.1007/s10570-020-034...
], postbiotics of lactic acid bacterium[6969 Shafipour Yordshahi, A., Moradi, M., Tajik, H., & Molaei, R. (2020). Design and preparation of antimicrobial meat wrapping nanopaper with bacterial cellulose and postbiotics of lactic acid bacteria. International Journal of Food Microbiology, 321, 108561. http://dx.doi.org/10.1016/j.ijfoodmicro.2020.108561. PMid:32078868.
http://dx.doi.org/10.1016/j.ijfoodmicro....
] and potato peel[7070 Xie, Y., Niu, X., Yang, J., Fan, R., Shi, J., Ullah, N., Feng, X., & Chen, L. (2020). Active biodegradable films based on the whole potato peel incorporated with bacterial cellulose and curcumin. International Journal of Biological Macromolecules, 150, 480-491. http://dx.doi.org/10.1016/j.ijbiomac.2020.01.291. PMid:32007551.
http://dx.doi.org/10.1016/j.ijbiomac.202...
]. Other BC applications in the food field can be found in Table 1.

Table 1
Exemples of BC applications in the world.

1.3.1.2 Brazil

In Brazil, the research groups have focused more on the development of edible films and food packaging. Viana et al.[108108 Viana, R. M., Sá, N. M. S. M., Barros, M. O., Borges, M. de F., & Azeredo, H. M. C. (2018). Nanofibrillated bacterial cellulose and pectin edible films added with fruit purees. Carbohydrate Polymers, 196, 27-32. http://dx.doi.org/10.1016/j.carbpol.2018.05.017. PMid:29891296.
http://dx.doi.org/10.1016/j.carbpol.2018...
] produced films with different ratios of nanofibrillated BC (NFBC) to pectin, with or without the addition of fruit purees. In their study, films (with or without purees) with higher NFBC contents showed improvement in physical properties and were proposed for use in food wrapping or coating.

Studies conducted by Malheiros et al.[109109 Malheiros, P. S., Jozala, A. F., Pessoa-Jr., A., Vila, M. M. D. C., Balcão, V. M., & Franco, B. D. G. M. (2018). Immobilization of antimicrobial peptides from Lactobacillus sakei subsp. sakei 2a in bacterial cellulose: structural and functional stabilization. Food Packaging and Shelf Life, 17, 25-29. http://dx.doi.org/10.1016/j.fpsl.2018.05.001.
http://dx.doi.org/10.1016/j.fpsl.2018.05...
] show that the immobilization of antimicrobial peptides from Lactobacillus sakei subsp. sakei 2a in BC is a promising strategy for the control of Listeria monocytogenes in foods. Similarly, a new material composed of BC/poly(3-hydroxybutyrate) with the addition of clove essential oil demonstrated a reduction of 65% in microbial growth and attractive properties for active food packaging[110110 Albuquerque, R. M. B., Meira, H. M., Silva, I. D. L., Silva, C. J. G., Almeida, F. C. G., & Amorim, J. D. P. … Sarubbo, L. A. (2020). Production of a bacterial cellulose/poly(3-hydroxybutyrate) blend activated with clove essential oil for food packaging. Polymers & Polymer Composites. In press. http://dx.doi.org/10.1177/0967391120912098.
http://dx.doi.org/10.1177/09673911209120...
].

In order to develop active composite films from cashew by-products, Sá et al.[111111 Sá, N. M. S. M., Mattos, A. L. A., Silva, L. M. A., Brito, E. S., Rosa, M. F., & Azeredo, H. M. C. (2020). From cashew byproducts to biodegradable active materials: bacterial cellulose-lignin-cellulose nanocrystal nanocomposite films. International Journal of Biological Macromolecules, 161, 1337-1345. http://dx.doi.org/10.1016/j.ijbiomac.2020.07.269. PMid:32777430.
http://dx.doi.org/10.1016/j.ijbiomac.202...
] produced BC from cashew juice and then they added nanocrystals of lignin and cellulose (both from cashew pruning fiber) to produce the film. Although lignin gave brown color and opacity, the films showed good mechanical properties and interesting antioxidant capacity. Other works involve the preparation of biodegradable films made from blends of potato starch/BC/ glycerol[112112 Almeida, D. M., Prestes, R. A., Pinheiro, L. A., Woiciechowski, A. L., & Wosiacki, G. (2013). Phisical, chemical and barrier properties in films made with bacterial celullose and potato starch blend. Polímeros, 23(4), 538-546. http://dx.doi.org/10.4322/polimeros.2013.038.
http://dx.doi.org/10.4322/polimeros.2013...
] and BC/ polycaprolactone acetone solution[113113 Barud, H. S., Ribeiro, S. J. L., Carone, C. L. P., Ligabue, R., Einloft, S., Queiroz, P. V. S., Borges, A. P. B., & Jahno, V. D. (2013). Optically transparent membrane based on bacterial cellulose/ polycaprolactone. Polímeros, 23(1), 135-138. http://dx.doi.org/10.1590/S0104-14282013005000018.
http://dx.doi.org/10.1590/S0104-14282013...
].

1.3.2 Electronic, electrochemical and magnetic field

1.3.2.1 World

In electronic field, BC has attracted great attention mainly due to depletion of non-renewable resources[114114 Amorim, J. D. P., Souza, K. C., Duarte, C. R., Silva Duarte, I., Ribeiro, F. A. S., Silva, G. S., Farias, P. M. A., Stingl, A., Costa, A. F. S., Vinhas, G. M., & Sarubbo, L. A. (2020). Plant and bacterial nanocellulose: production, properties and applications in medicine, food, cosmetics, electronics and engineering: a review. Environmental Chemistry Letters, 18(3), 851-869. http://dx.doi.org/10.1007/s10311-020-00989-9.
http://dx.doi.org/10.1007/s10311-020-009...
]. Moreover, due to its porous nanofibrous network structure, BC is used as a flexible matrix for developing biomaterials with desired properties. BC-based materials have been developed using conducting polymers, graphene, graphene oxide, carbon nanotube and carbon nanofiber (Table 1). Their application occurs especially in flexible supercapacitors, ion battery, fuel cell, and other electrochemical devices[115115 Chen, X., Yuan, F., Zhang, H., Huang, Y., Yang, J., & Sun, D. (2016). Recent approaches and future prospects of bacterial cellulose-based electroconductive materials. Journal of Materials Science, 51(12), 5573-5588. http://dx.doi.org/10.1007/s10853-016-9899-2.
http://dx.doi.org/10.1007/s10853-016-989...
].

Actually, several works have combined BC nanofibers with conducting polymers as polyaniline and polypyrrole. When Graphene/Carbon Nanotube/Bacterial Cellulose (RGO/CNT/BC) architecture was designed as substrate for loading polypyrrole (PPy), Bai et al.[116116 Bai, Y., Liu, R., Li, E., Li, X., Liu, Y., & Yuan, G. (2019). Graphene/Carbon Nanotube/Bacterial Cellulose assisted supporting for polypyrrole towards flexible supercapacitor applications. Journal of Alloys and Compounds, 777, 524-530. http://dx.doi.org/10.1016/j.jallcom.2018.10.376.
http://dx.doi.org/10.1016/j.jallcom.2018...
] showed that flexible supercapacitor exhibits stable electrochemical performance under bending and flat conditions. Similarly, Rebelo et al.[117117 Rebelo, A. R., Liu, C., Schäfer, K. H., Saumer, M., Yang, G., & Liu, Y. (2019). Poly(4-vinylaniline)/polyaniline bilayer-functionalized bacterial cellulose for flexible electrochemical biosensors. Langmuir, 35(32), 10354-10366. http://dx.doi.org/10.1021/acs.langmuir.9b01425. PMid:31318565.
http://dx.doi.org/10.1021/acs.langmuir.9...
] synthesized an electrically conductive BC/Polyvinylaniline/Polyaniline (BC/PVAN/PANI) nanobiosensor for potential use in nerve regenerative medicine, which demands both electroactivity and biocompatibility. BC has also become a valuable for production of lithium-ion batteries (LIB).

Yuan et al.[118118 Yuan, F., Huang, Y., Qian, J., Rahman, M. M., Ajayan, P. M., & Sun, D. (2020). Free-standing SnS/carbonized cellulose film as durable anode for lithium-ion batteries. Carbohydrate Polymers, 255, 117400. http://dx.doi.org/10.1016/j.carbpol.2020.117400. PMid:33436227.
http://dx.doi.org/10.1016/j.carbpol.2020...
] designed free-standing films of tin sulfide (SnS) nanosheets distributed uniformly on carbonized BC (CBC) nanofibers. LIB using SnS/CBC as anode could be a promising electrode material, since exhibited high capacity, excellent cycling stability and high-rate capability. In order to develop proton exchange membranes (PEMs) for application in polymer electrolyte fuel cells (PEFC), Vilela et al.[119119 Vilela, C., Silva, A. C. Q., Domingues, E. M., Gonçalves, G., Martins, M. A., Figueiredo, F. M. L., Santos, S. A. O., & Freire, C. S. R. (2020). Conductive polysaccharides-based proton-exchange membranes for fuel cell applications: the case of bacterial cellulose and fucoidan. Carbohydrate Polymers, 230, 115604. http://dx.doi.org/10.1016/j.carbpol.2019.115604. PMid:31887959.
http://dx.doi.org/10.1016/j.carbpol.2019...
] combined BC (support), fucoidan (polyelectrolyte) and tannic acid (cross-linker). The membranes presented thermal-oxidative stability (180-200 °C), good dynamic mechanical performance and the protonic conductivity increased with the increase in relative humidity. The authors concluded that BC/fucoidan membranes have potential as eco-friendly alternatives to other PEMs for application in PEFCs.

1.3.2.2 Brazil

In Brazil, Müller et al.[120120 Müller, D., Cercená, R., Gutiérrez Aguayo, A. J., Porto, L. M., Rambo, C. R., & Barra, G. M. O. (2016). Flexible PEDOT-nanocellulose composites produced by in situ oxidative polymerization for passive components in frequency filters. Journal of Materials Science Materials in Electronics, 27(8), 8062-8067. http://dx.doi.org/10.1007/s10854-016-4804-y.
http://dx.doi.org/10.1007/s10854-016-480...
] carried out an in situ oxidative polymerization of EDOT on nanocellulose fibers to obtain PEDOT-nanocellulose flexible composites. The nanocomposites showed an increase in electrical conductivity and in elongation at break, with a lower thermal stability when compared to pure BC. Therefore, the authors concluded that the flexible membranes have potential use for flexible organic electronics.

In a recent study, Legnani et al.[121121 Legnani, C., Barud, H. S., Caiut, J. M. A., Calil, V. L., Maciel, I. O., Quirino, W. G., Ribeiro, S. J. L., & Cremona, M. (2019). Transparent bacterial cellulose nanocomposites used as substrate for organic light-emitting diodes. Journal of Materials Science Materials in Electronics, 30(18), 16718-16723. http://dx.doi.org/10.1007/s10854-019-00979-w.
http://dx.doi.org/10.1007/s10854-019-009...
] produced multifunctional membranes based on BC and an organic-inorganic sol, composed of boehmite (Boe) nanoparticles and epoxy modified siloxane (GTPS), to be used as substrates in organic light-emitting diodes (OLEDs). Then, they covered the BC/Boe-GTPS with silicon dioxide (SiO2) and indium tin oxide (ITO), thereby obtaining eco-friendly, biocompatible substrates comparable to fabricated commercial glass substrate.

Conductive composite membranes of BC and polyaniline, using different oxidizing agents like FeCl3.6H2O[122122 Müller, D., Mandelli, J. S., Marins, J. A., Soares, B. G., Porto, L. M., Rambo, C. R., & Barra, G. M. O. (2012). Electrically conducting nanocomposites: preparation and properties of polyaniline (PAni)-coated bacterial cellulose nanofibers (BC). Cellulose, 19(5), 1645-1654. http://dx.doi.org/10.1007/s10570-012-9754-9.
http://dx.doi.org/10.1007/s10570-012-975...
] and ammonium peroxydisulfate[123123 Marins, J. A., Soares, B. G., Dahmouche, K., Ribeiro, S. J. L., Barud, H., & Bonemer, D. (2011). Structure and properties of conducting bacterial cellulose-polyaniline nanocomposites. Cellulose, 18(5), 1285-1294. http://dx.doi.org/10.1007/s10570-011-9565-4.
http://dx.doi.org/10.1007/s10570-011-956...
], may allow for important technological applications, such as sensors, electronic devices, intelligent clothes, flexible electrodes and tissue engineering scaffolds. Other interesting approachs exploit the intrinsic properties of BC, combined with the physical and chemical characteristics of compounds such as nanoparticulated Boe and GTPS[124124 Barud, H. S., Tercjak, A., Gutierrez, J., Viali, W. R., Nunes, E. S., Ribeiro, S. J. L., Jafellici, M., Nalin, M., & Marques, R. F. C. (2015). Biocellulose-based flexible magnetic paper. Journal of Applied Physics, 117(17), 1-5. http://dx.doi.org/10.1063/1.4917261.
http://dx.doi.org/10.1063/1.4917261...
], polypyrrole[125125 Müller, D., Rambo, C. R., Porto, L. M., & Barra, G. M. O. (2011). Chemical in situ polymerization of polypyrrole on bacterial cellulose nanofibers. Synthetic Metals, 161(1-2), 106-111. http://dx.doi.org/10.1016/j.synthmet.2010.11.005.
http://dx.doi.org/10.1016/j.synthmet.201...
] and laponite[126126 Perotti, G. F., Barud, H. S., Messaddeq, Y., Ribeiro, S. J. L., & Constantino, V. R. L. (2011). Bacterial cellulose-laponite clay nanocomposites. Polymer, 52(1), 157-163. http://dx.doi.org/10.1016/j.polymer.2010.10.062.
http://dx.doi.org/10.1016/j.polymer.2010...
], to produce new materials that may be suitable for biomedical and electronic applications. Other studies are shown in Table 2.

Table 2
Summary of studies of BC applications in electronics/electrochemical/magnetic field.

1.3.3 Biomedical area

1.3.3.1 World

Most BC studies are currently focused in the biomedical field, where the multifunctionality of this polymer has been shown mainly through the development of biomaterials as wound dressing, scaffold for tissue engineering and drug delivery[135135 Ahmed, J., Gultekinoglu, M., & Edirisinghe, M. (2020). Bacterial cellulose micro-nano fibres for wound healing applications. Biotechnology Advances, 41, 107549. http://dx.doi.org/10.1016/j.biotechadv.2020.107549. PMid:32302653.
http://dx.doi.org/10.1016/j.biotechadv.2...
] (Table 1).

BC membranes have several advantages that allow it to be considered as an ideal wound dressing material. It forms a bacteriological barrier that allows for gas exchange and reduces pain, it maintains moisture of the environment, its transparency favors direct visualization of the wound, and it also reduces the treatment time and the costs of hospitalization of patients with burns and chronic wounds[88 Picheth, G. F., Pirich, C. L., Sierakowski, M. R., Woehl, M. A., Sakakibara, C. N., de Souza, C. F., Martin, A. A., da Silva, R., & de Freitas, R. A. (2017). Bacterial cellulose in biomedical applications: a review. International Journal of Biological Macromolecules, 104(Pt A), 97-106. http://dx.doi.org/10.1016/j.ijbiomac.2017.05.171. PMid:28587970.
http://dx.doi.org/10.1016/j.ijbiomac.201...
,136136 Fischer, M. R., Garcia, M. C. F., Nogueira, A. L., Porto, L. M., Schneider, A. L. dos S., & Pezzin, A. P. T. (2017). Biossíntese e caracterização de nanocelulose bacteriana para engenharia de tecidos. Revista Materia, 22(3), e11934. http://dx.doi.org/10.1590/s1517-707620170005.0270.
http://dx.doi.org/10.1590/s1517-70762017...
]. The direct use of BC itself has no antimicrobial activity to prevent wound infection[137137 Barud, H. S., Regiani, T., Marques, R. F. C., Lustri, W. R., Messaddeq, Y., & Ribeiro, S. J. L. (2011). Antimicrobial bacterial cellulose-silver nanoparticles composite membranes. Journal of Nanomaterials, 2011, 1-8. http://dx.doi.org/10.1155/2011/721631.
http://dx.doi.org/10.1155/2011/721631...
]; therefore, recently, several studies have incorporated active compounds into its structure to improve the properties and functionalities.

Cao et al.[138138 Cao, Y., Liu, M. Y., Xue, Z. W., Qiu, Y., Li, J., Wang, Y., & Wu, Q. K. (2019). Surface-structured bacterial cellulose loaded with hUSCs accelerate skin wound healing by promoting angiogenesis in rats. Biochemical and Biophysical Research Communications, 516(4), 1167-1174. http://dx.doi.org/10.1016/j.bbrc.2019.06.161. PMid:31284954.
http://dx.doi.org/10.1016/j.bbrc.2019.06...
] evaluated the potential use of a structured surface BC biomaterial incorporated with human urine-derived stem cells for use as wound dressing. The in vivo results were promising for this combination, since the healing rate was significantly higher compared to the control. BC was also incorporated with sodium alginate, chitosan and copper sulfate, in order to provide an antimicrobial for use as wound dressing. The material obtained showed antimicrobial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli[139139 Wichai, S., Chuysinuan, P., Chaiarwut, S., Ekabutr, P., & Supaphol, P. (2019). Development of bacterial cellulose/alginate/chitosan composites incorporating copper (II) sulfate as an antibacterial wound dressing. Journal of Drug Delivery Science and Technology, 51, 662-671. http://dx.doi.org/10.1016/j.jddst.2019.03.043.
http://dx.doi.org/10.1016/j.jddst.2019.0...
]. In another study, BC was combined with poly(methylmethacrylate) (PMMA) in order to obtain biocompatible and biodegradable bandages to support wound healing. Preliminary analyses of swelling characteristics and mechanical properties indicated that this biomaterial is a promising candidate for biomedical applications[140140 Altun, E., Aydogdu, M. O., Koc, F., Crabbe-Mann, M., Brako, F., Kaur-Matharu, R., Ozen, G., Kuruca, S. E., Edirisinghe, U., Gunduz, O., & Edirisinghe, M. (2018). Novel making of bacterial cellulose blended polymeric fiber bandages. Macromolecular Materials and Engineering, 303(3), 1700607. http://dx.doi.org/10.1002/mame.201700607.
http://dx.doi.org/10.1002/mame.201700607...
].

Tissue cells, scaffold and growth factors are extremely important factors in the success of tissue engineering. Scaffolding is used to support the newly formed tissues, interact with cells and release substances necessary for cell growth. Since BC's morphological structure has a high degree of purity, excellent biocompatibility and high tensile strength, BC has been extensively studied as a candidate for tissue engineering[141141 Wu, J., Yin, N., Chen, S., Weibel, D. B., & Wang, H. (2019). Simultaneous 3D cell distribution and bioactivity enhancement of bacterial cellulose (BC) scaffold for articular cartilage tissue engineering. Cellulose, 26(4), 2513-2528. http://dx.doi.org/10.1007/s10570-018-02240-9.
http://dx.doi.org/10.1007/s10570-018-022...
]. Ahn et al.[142142 Ahn, S. J., Shin, Y. M., Kim, S. E., Jeong, S. I., Jeong, J. O., Park, J. S., Gwon, H.-J., Seo, D. E., Nho, Y.-C., Kang, S. S., Kim, C.-Y., Huh, J.-B., & Lim, Y.-M. (2015). Characterization of hydroxyapatite-coated bacterial cellulose scaffold for bone tissue engineering. Biotechnology and Bioprocess Engineering, 20(5), 948-955. http://dx.doi.org/10.1007/s12257-015-0176-z.
http://dx.doi.org/10.1007/s12257-015-017...
] developed a structure of BC coated with hydroxyapatite (HA) for bone tissue regeneration. The bone regeneration capacity was assessed using a rat calvary defect model. The results showed that both scaffold (BC coated with BC and HA) were effective in bone formation derived from existing bone, in addition, a new bone was found inside the scaffold.

Torgbo and Sukyai[143143 Torgbo, S., & Sukyai, P. (2019). Fabrication of microporous bacterial cellulose embedded with magnetite and hydroxyapatite nanocomposite scaffold for bone tissue engineering. Materials Chemistry and Physics, 237, 121868. http://dx.doi.org/10.1016/j.matchemphys.2019.121868.
http://dx.doi.org/10.1016/j.matchemphys....
] synthesized a nanocomposite by combining BC, hydroxyapatite (HA) and magnetite nanoparticles (Fe3O4) through ultrasonic irradiation. The scaffold was not toxic to mouse fibroblast cells and was also biocompatible to osteoblasts attachment and proliferation. Aiming to promote the formation of blood vessels, Wang et al.[144144 Wang, B., Lv, X., Chen, S., Li, Z., Yao, J., Peng, X., Feng, C., Xu, Y., & Wang, H. (2018). Use of heparinized bacterial cellulose based scaffold for improving angiogenesis in tissue regeneration. Carbohydrate Polymers, 181, 948-956. http://dx.doi.org/10.1016/j.carbpol.2017.11.055. PMid:29254059.
http://dx.doi.org/10.1016/j.carbpol.2017...
] modified BC/gelatin (BC/G) scaffold with heparin and studied its skill of promoting angiogenesis in terms of vascular endothelial growth factor (VEGF) release. The scaffold provided prolonged VEGF release. Proliferation and migration (in vitro cellular assay) were observed in the presence of VEGF. Furthermore, heparinized scaffolds loaded with VEGF (V-BC/G/H) improved the angiogenesis compared to BC/G scaffold.

During the past few years, the number of studies related to the incorporation of drugs into BC membranes has increased. The most common drugs to be loaded in BC are non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics[3030 Blanco Parte, F. G., Santoso, S. P., Chou, C. C., Verma, V., Wang, H. T., Ismadji, S., & Cheng, K. C. (2020). Current progress on the production, modification, and applications of bacterial cellulose. Critical Reviews in Biotechnology, 40(3), 397-414. http://dx.doi.org/10.1080/07388551.2020.1713721. PMid:31937141.
http://dx.doi.org/10.1080/07388551.2020....
]. Shao et al.[145145 Shao, W., Liu, H., Wang, S., Wu, J., Huang, M., Min, H., & Liu, X. (2016). Controlled release and antibacterial activity of tetracycline hydrochloride-loaded bacterial cellulose composite membranes. Carbohydrate Polymers, 145, 114-120. http://dx.doi.org/10.1016/j.carbpol.2016.02.065. PMid:27106158.
http://dx.doi.org/10.1016/j.carbpol.2016...
] loaded BC membrane with tetracycline hydrochloride (TCH). The biomaterial showed biocompatibility, high antibacterial activity and it was not toxic in HEK293 cells. Similarly, BC, PVA and chitosan mono and multilayer films were effective for controlled release of ibuprofen sodium salt[146146 Pavaloiu, R. D., Stoica-Guzun, A., Stroescu, M., Jinga, S. I., & Dobre, T. (2014). Composite films of poly(vinyl alcohol)-chitosan-bacterial cellulose for drug controlled release. International Journal of Biological Macromolecules, 68, 117-124. http://dx.doi.org/10.1016/j.ijbiomac.2014.04.040. PMid:24769089.
http://dx.doi.org/10.1016/j.ijbiomac.201...
].

1.3.3.2 Brazil

In Brazil, although considerable research has been devoted to wound dressings and tissue engineering, the incorporation and modification of BC with countless substances has further expanded the spectrum of applications in the biomedical area (Table 3). For example, BC and carboxymethylcelullose (CMC) biocomposites loaded with methotrexate were developed in order to evaluate their effectiveness as a drug delivery system, as an alternative for the topical treatment of psoriasis. The results showed that different amounts of DS-CMC can generate distinct biomaterials, to be applied through the cutaneous route at different stages of evolution of a pathology[160160 Fontes, M. L., Meneguin, A. B., Tercjak, A., Gutierrez, J., Cury, B. S. F., Santos, A. M., Ribeiro, S. J. L., & Barud, H. S. (2018). Effect of in situ modification of bacterial cellulose with carboxymethylcellulose on its nano/microstructure and methotrexate release properties. Carbohydrate Polymers, 179, 126-134. http://dx.doi.org/10.1016/j.carbpol.2017.09.061. PMid:29111035.
http://dx.doi.org/10.1016/j.carbpol.2017...
].

Table 3
Summary of studies of potential applications of BC in the biomedical area.

In the case of application for cancer therapeutics, photodynamic therapy (PDT) has emerged as an innovative therapeutic modality, focused mainly on skin cancer treatment. Peres et al.[161161 Peres, M. F. S., Nigoghossian, K., Primo, F. L., Saska, S., Capote, T. S. O., Caminaga, R. M. S., Messaddeq, Y., Ribeiro, S. J. L., & Tedesco, A. C. (2016). Bacterial cellulose membranes as a potential drug delivery system for photodynamic therapy of skin cancer. Journal of the Brazilian Chemical Society, 27(11), 1949-1959. http://dx.doi.org/10.5935/0103-5053.20160080.
http://dx.doi.org/10.5935/0103-5053.2016...
] utilized chloroaluminum phthalocyanine (ClAlPc) as a photosensitizer and impregnated BC membranes with it, with the goal of developing such applications as a drug delivery system for PDT skin cancer protocols. Photophysical studies of BC-ClAlPc showed that the properties of photosensitizer were not affected, and the result of the cell viability test using Chinese hamster ovary cells (CHO-K1) demonstrated their potential for safe biological use. Another study of great relevance is related to Leishmaniasis, a group of parasitic diseases caused by protozoa of the genus Leishmania. Brazil, together with nine other countries, is responsible for 70-75% of the global Cutaneous Leishmaniasis (CL) occurrence. In this context, Celes et al.[162162 Celes, F. S., Trovatti, E., Khouri, R., Van Weyenbergh, J., Ribeiro, S. J. L., Borges, V. M., Barud, H. S., & de Oliveira, C. I. (2016). DETC-based bacterial cellulose bio-curatives for topical treatment of cutaneous leishmaniasis. Scientific Reports, 6(1), 38330. http://dx.doi.org/10.1038/srep38330. PMid:27922065.
http://dx.doi.org/10.1038/srep38330...
] described a topical formulation by incorporating Diethyldithiocarbamate (DETC), a superoxide dismutase 1 inhibitor, into BC membranes for CL treatment. BC-DETC did not cause noticeable toxic effects and resulted in parasite killing. The topical formulation significantly reduced the lesion size, inflammatory response at the infection site and parasite load, highlighting its availability for treatment of CL.

Dengue is an endemic disease widespread throughout the tropics, in which the regions most affected are the Americas, South-East Asia and Western Pacific[163163 Picheth, G. F., Pirich, C. L., Sierakowski, M. R., Woehl, M. A., Sakakibara, C. N., Souza, C. F., Martin, A. A., Silva, R., & Freitas, R. A. (2017). Bacterial cellulose in biomedical applications: a review. International Journal of Biological Macromolecules, 104(Pt A), 97-106. http://dx.doi.org/10.1016/j.ijbiomac.2017.05.171. PMid:28587970.
http://dx.doi.org/10.1016/j.ijbiomac.201...
,164164 World Health Organization (WHO) (2016). Dengue Control: Epidemiology (2020, September 15). Retrieved from https://www.who.int/denguecontrol/epidemiology/en/
https://www.who.int/denguecontrol/epidem...
]. According to the World Health Organization[164164 World Health Organization (WHO) (2016). Dengue Control: Epidemiology (2020, September 15). Retrieved from https://www.who.int/denguecontrol/epidemiology/en/
https://www.who.int/denguecontrol/epidem...
], in Brazil, the average of number of reported dengue infections was over 100 thousand between 2010-2016. Since misdiagnosis is still a problem[165165 Bhatt, S., Gething, P. W., Brady, O. J., Messina, J. P., Farlow, A. W., Moyes, C. L., Drake, J. M., Brownstein, J. S., Hoen, A. G., Sankoh, O., Myers, M. F., George, D. B., Jaenisch, T., Wint, G. R., Simmons, C. P., Scott, T. W., Farrar, J. J., & Hay, S. I. (2013). The global distribution and burden of dengue. Nature, 496(7446), 504-507. http://dx.doi.org/10.1038/nature12060. PMid:23563266.
http://dx.doi.org/10.1038/nature12060...
], Picheth et al.[163163 Picheth, G. F., Pirich, C. L., Sierakowski, M. R., Woehl, M. A., Sakakibara, C. N., Souza, C. F., Martin, A. A., Silva, R., & Freitas, R. A. (2017). Bacterial cellulose in biomedical applications: a review. International Journal of Biological Macromolecules, 104(Pt A), 97-106. http://dx.doi.org/10.1016/j.ijbiomac.2017.05.171. PMid:28587970.
http://dx.doi.org/10.1016/j.ijbiomac.201...
] proposed that diagnostic assays were more sensible, faster and less expensive for this disease. For this purpose, piezoelectric sensors were coated with thin BC nanocrystals (CN) in order to facilitate anchoring of monoclonal immunoglobulin G (IgGNS1) against NS1 dengue antigen. The authors observed that biosensors, compared to cellulosic surfaces, increased the total IgGNS1 immobilized mass by twofold and reduced the need for sample dilution by tenfold. Lastly, they concluded the sensors can be used qualitatively in clinical diagnosis after suitable validation.

In the ophthalmological area, Coelho et al.[166166 Coelho, F., Vale Braido, G. V., Cavicchioli, M., Mendes, L. S., Specian, S. S., Franchi, L. P., Lima Ribeiro, S. J., Messaddeq, Y., Scarel-Caminaga, R. M., & O Capote, T. S. (2019). Toxicity of therapeutic contact lenses based on bacterial cellulose with coatings to provide transparency. Contact Lens & Anterior Eye, 42(5), 512-519. http://dx.doi.org/10.1016/j.clae.2019.03.006. PMid:30948195.
http://dx.doi.org/10.1016/j.clae.2019.03...
] developed and evaluated the cytoxicity, genotoxicity and mutagenicity of contact lenses based on BC, coated with either glycidoxypropyltrimethoxysilane (H) or chitosan (Q), incorporating ciclodextrin (CD) to release diclofenac sodium (DS) or ciprofloxacin (CP). Functionalized BC lenses safely allowed for the bioavailability of ophthalmic drugs, in which only BC-H-CD-DS presented cytotoxic and genotoxic effects and BC-Q-CD-DS showed cytotoxic effects. Therefore, the authors suggested other specific tests with corneal lineage to ensure safe ophthalmologic use. Additionally, unmodified BC also proved to be a useful material in medical displacement procedures of the vocal folds. Souza et al.[167167 Souza, F. C., Olival-Costa, H., da Silva, L., Pontes, P. A., & Lancellotti, C. L. P. (2011). Bacterial cellulose as laryngeal medialization material: an experimental study. Journal of Voice, 25(6), 765-769. http://dx.doi.org/10.1016/j.jvoice.2010.07.005. PMid:21051197.
http://dx.doi.org/10.1016/j.jvoice.2010....
] demonstrated that laryngeal medialization with BC in the larynx of rabbits did not cause rejection or absorption and it was stable over a long period.

In order to obtain antimicrobial properties, Brazilian researchers have incorporated different antimicrobial to BC. For example, silver nanoparticles composites[137137 Barud, H. S., Regiani, T., Marques, R. F. C., Lustri, W. R., Messaddeq, Y., & Ribeiro, S. J. L. (2011). Antimicrobial bacterial cellulose-silver nanoparticles composite membranes. Journal of Nanomaterials, 2011, 1-8. http://dx.doi.org/10.1155/2011/721631.
http://dx.doi.org/10.1155/2011/721631...
,168168 Maria, L. C. S., Santos, A. L. C., Oliveira, P. C., Valle, A. S. S., Barud, H. S., Messaddeq, Y., & Ribeiro, S. J. L. (2010). Preparation and antibacterial activity of silver nanoparticles impregnated in bacterial cellulose. Polímeros: Ciência e Tecnologia, 20(1), 72-77. http://dx.doi.org/10.1590/S0104-14282010005000001.
http://dx.doi.org/10.1590/S0104-14282010...
] (cerium nitrate and silver nanoparticles[136136 Fischer, M. R., Garcia, M. C. F., Nogueira, A. L., Porto, L. M., Schneider, A. L. dos S., & Pezzin, A. P. T. (2017). Biossíntese e caracterização de nanocelulose bacteriana para engenharia de tecidos. Revista Materia, 22(3), e11934. http://dx.doi.org/10.1590/s1517-707620170005.0270.
http://dx.doi.org/10.1590/s1517-70762017...
], copper nitrate (Cu(NO3)2)[169169 Araújo, I. M. S., Silva, R. R., Pacheco, G., Lustri, W. R., Tercjak, A., Gutierrez, J., Santos, J. R., Jr., Azevedo, F. H. C., Figuêredo, G. S., Vega, M. L., Ribeiro, S. J. L., & Barud, H. S. (2018). Hydrothermal synthesis of bacterial cellulose–copper oxide nanocomposites and evaluation of their antimicrobial activity. Carbohydrate Polymers, 179, 341-349. http://dx.doi.org/10.1016/j.carbpol.2017.09.081. PMid:29111060.
http://dx.doi.org/10.1016/j.carbpol.2017...
] and ceftriaxone[170170 Lazarini, S. C., Aquino, R., Amaral, A. C., Corbi, F. C. A., Corbi, P. P., Barud, H. S., & Lustri, W. R. (2016). Characterization of bilayer bacterial cellulose membranes with different fiber densities: a promising system for controlled release of the antibiotic ceftriaxone. Cellulose, 23(1), 737-748. http://dx.doi.org/10.1007/s10570-015-0843-4.
http://dx.doi.org/10.1007/s10570-015-084...
]) have been incorporated in BC membranes and exhibited strong antimicrobial activity against Gram-negative (Pseudomonas aeruginosa, Salmonella and Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, which are commonly found in skin infections.

The antimicrobial activity and the wound healing properties of novel BC containing Brazilian propolis was also demonstrated by Wei et al.[171171 Wei, B., Yang, G., & Hong, F. (2011). Preparation and evaluation of a kind of bacterial cellulose dry films with antibacterial properties. Carbohydrate Polymers, 84(1), 533-538. http://dx.doi.org/10.1016/j.carbpol.2010.12.017.
http://dx.doi.org/10.1016/j.carbpol.2010...
], Marquele-Oliveira et al.[172172 Marquele-Oliveira, F., da Silva Barud, H., Torres, E. C., Machado, R. T. A., Caetano, G. F., Leite, M. N., Frade, M. A. C., Ribeiro, S. J. L., & Berretta, A. A. (2019). Development, characterization and pre-clinical trials of an innovative wound healing dressing based on propolis (EPP-AF®)-containing self-microemulsifying formulation incorporated in biocellulose membranes. International Journal of Biological Macromolecules, 136, 570-578. http://dx.doi.org/10.1016/j.ijbiomac.2019.05.135. PMid:31226369.
http://dx.doi.org/10.1016/j.ijbiomac.201...
] and Picolotto et al.[173173 Picolotto, A., Pergher, D., Pereira, G. P., Machado, K. G., Barud, H. S., Roesch-Ely, M., Gonzalez, M. H., Tasso, L., Figueiredo, J. G., & Moura, S. (2019). Bacterial cellulose membrane associated with red propolis as phytomodulator: improved healing effects in experimental models of diabetes mellitus. Biomedicine and Pharmacotherapy, 112, 108640. http://dx.doi.org/10.1016/j.biopha.2019.108640. PMid:30784929.
http://dx.doi.org/10.1016/j.biopha.2019....
]. The first two authors proved the antimicrobial efficacy of in vitro BC/propolis membranes against Gram-negative and Gram-positive bacteria; their in vitro studies suggested that the biomaterial may promote fast re-epithelization and tissue organization, setting up a potential therapy for infected wounds. The accelerated wound healing process in a diabetic mouse model was also evidenced by Picolotto et al.[173173 Picolotto, A., Pergher, D., Pereira, G. P., Machado, K. G., Barud, H. S., Roesch-Ely, M., Gonzalez, M. H., Tasso, L., Figueiredo, J. G., & Moura, S. (2019). Bacterial cellulose membrane associated with red propolis as phytomodulator: improved healing effects in experimental models of diabetes mellitus. Biomedicine and Pharmacotherapy, 112, 108640. http://dx.doi.org/10.1016/j.biopha.2019.108640. PMid:30784929.
http://dx.doi.org/10.1016/j.biopha.2019....
].

Other approaches favoring wound healing have also been developed. Picheth et al.[5151 Picheth, G. F., Sierakowski, M. R., Woehl, M. A., Ono, L., Cofré, A. R., Vanin, L. P., Pontarolo, R., & De Freitas, R. A. (2014). Lysozyme-triggered epidermal growth factor release from bacterial cellulose membranes controlled by smart nanostructured films. Journal of Pharmaceutical Sciences, 103(12), 3958-3965. http://dx.doi.org/10.1002/jps.24205. PMid:25308839.
http://dx.doi.org/10.1002/jps.24205...
] assembled a novel wound dressing sensitive to lysozyme by depositing nanopolymeric chitosan and alginate films onto oxidized BC membranes incorporated with epidermal growth factor (EGF). The proposed system proved to be effective as wound dressing and presented a local delivery mechanism to recognize infections and to respond with a burst of EGF release. Wound dressing based on BC/collagen hydrogel in rat dorsum stimulated better wound healing than commercial collagenase and control group (untreated wound)[174174 Moraes, P. R. F. S., Saska, S., Barud, H., Lima, L. R., Martins, V. C. A., Plepis, A. M. G., Ribeiro, S. J. L., & Gaspar, A. M. M. (2016). Bacterial cellulose/collagen hydrogel for wound healing. Materials Research, 19(1), 106-116. http://dx.doi.org/10.1590/1980-5373-MR-2015-0249.
http://dx.doi.org/10.1590/1980-5373-MR-2...
].

As previously commented, BC has also become a promising biopolymer for tissue engineering and regenerative medicine applications; many studies have been conducted to synthesize new biomaterials based on BC (Table 3). Saska et al.[175175 Saska, S., Barud, H. S., Gaspar, A. M. M., Marchetto, R., Ribeiro, S. J. L., & Messaddeq, Y. (2011). Bacterial cellulose-hydroxyapatite nanocomposites for bone regeneration. International Journal of Biomaterials, 2011, 175362. http://dx.doi.org/10.1155/2011/175362. PMid:21961004.
http://dx.doi.org/10.1155/2011/175362...
] developed and evaluated the biological properties of bacterial cellulose-hydroxyapatite (BC-HA) nanocomposite membranes in noncritical bone defects in rat tibiae at 1, 4, and 16 weeks. BC-HA composites have presented properties similar to that of physiological bone and have accelerated new bone formation of rat tibiae, without showing inflammatory reaction. Furthermore, the authors concluded that the membranes exhibited slow reabsorption, suggesting that the material takes longer to be completely reabsorbed. Afterwards, Saska et al.[176176 Saska, S., Scarel-Caminaga, R. M., Teixeira, L. N., Franchi, L. P., Dos Santos, R. A., Gaspar, A. M., de Oliveira, P. T., Rosa, A. L., Takahashi, C. S., Messaddeq, Y., Ribeiro, S. J., & Marchetto, R. (2012). Characterization and in vitro evaluation of bacterial cellulose membranes functionalized with osteogenic growth peptide for bone tissue engineering. Journal of Materials Science. Materials in Medicine, 23(9), 2253-2266. http://dx.doi.org/10.1007/s10856-012-4676-5. PMid:22622695.
http://dx.doi.org/10.1007/s10856-012-467...
] demonstrated that the peptide (osteogenic growth peptide (OGP) and its C-terminal pentapeptide OGP (10-14)) incorporation did not change the BC properties. Furthermore, in vitro assays revealed BC membranes influenced osteogenic cell proliferation and do not present cytotoxic, genotoxic or mutagenic action.

Similarly, Coelho et al.[177177 Coelho, F., Cavicchioli, M., Specian, S. S., Scarel-Caminaga, R. M., Penteado, L. A., Medeiros, A. I., Ribeiro, S. J. L., & Capote, T. S. O. (2019). Bacterial cellulose membrane functionalized with hydroxiapatite and anti-bone morphogenetic protein 2: A promising material for bone regeneration. PLoS One, 14(8), e0221286. http://dx.doi.org/10.1371/journal.pone.0221286. PMid:31425530.
http://dx.doi.org/10.1371/journal.pone.0...
] associated BC, HA and anti-bone morphogenetic protein antibody (anti-BMP-2) (BC-HA-anti-BMP-2), and did not observe toxicity of the membranes in MC3T3-E1 cells. BC-HA-anti-BMP-2 increased the expression of genes related to bone repair, the mineralization nodules and the levels of alkaline phosphatase activity when compared to the control group. Biocompatibility tests of BC, BC-HA and PTFE (polytetrafluoroethylene) using rats (Wistar) complemented prior studies[175175 Saska, S., Barud, H. S., Gaspar, A. M. M., Marchetto, R., Ribeiro, S. J. L., & Messaddeq, Y. (2011). Bacterial cellulose-hydroxyapatite nanocomposites for bone regeneration. International Journal of Biomaterials, 2011, 175362. http://dx.doi.org/10.1155/2011/175362. PMid:21961004.
http://dx.doi.org/10.1155/2011/175362...
,176176 Saska, S., Scarel-Caminaga, R. M., Teixeira, L. N., Franchi, L. P., Dos Santos, R. A., Gaspar, A. M., de Oliveira, P. T., Rosa, A. L., Takahashi, C. S., Messaddeq, Y., Ribeiro, S. J., & Marchetto, R. (2012). Characterization and in vitro evaluation of bacterial cellulose membranes functionalized with osteogenic growth peptide for bone tissue engineering. Journal of Materials Science. Materials in Medicine, 23(9), 2253-2266. http://dx.doi.org/10.1007/s10856-012-4676-5. PMid:22622695.
http://dx.doi.org/10.1007/s10856-012-467...
] which displayed that BC and BC/HA materials have the same inflammatory pattern when compared to PTFE, thus proving to be biocompatible materials[178178 Massari, K. V., Marinho, G. O., Silva, J. L., Holgado, L. A., Leão, A. L., Chaves, M. R. M., & Kinoshita, A. (2015). Tissue reaction after subcutaneous implantation of a membrane composed of bacterial cellulose embedded with hydroxyapatite. Dental, Oral, and Craniofacial Research, 1(2), 25-30. http://dx.doi.org/10.15761/docr.1000106.
http://dx.doi.org/10.15761/docr.1000106...
].

Composites based on collagen have demonstrated improvement of the biological and mechanical properties in bone tissue engineering. This protein is plentiful in the natural extracellular matrix (ECM) and in the human body, in addition to stimulating the regeneration process[179179 Saska, S., Teixeira, L. N., Castro Raucci, L. M. S., Scarel-Caminaga, R. M., Franchi, L. P., Santos, R. A., Santagneli, S. H., Capela, M. V., Oliveira, P. T., Takahashi, C. S., Gaspar, A. M. M., Messaddeq, Y., Ribeiro, S. J. L., & Marchetto, R. (2017). Nanocellulose-collagen-apatite composite associated with osteogenic growth peptide bone regeneration. International Journal of Biological Macromolecules, 103, 467-476. http://dx.doi.org/10.1016/j.ijbiomac.2017.05.086. PMid:28527999.
http://dx.doi.org/10.1016/j.ijbiomac.201...
]. Based on this, Saska et al.[180180 Saska, S., Teixeira, L. N., Tambasco de Oliveira, P., Minarelli Gaspar, A. M., Lima Ribeiro, S. J., Messaddeq, Y., & Marchetto, R. (2012). Bacterial cellulose-collagen nanocomposite for bone tissue engineering. Journal of Materials Chemistry, 22(41), 22102-22112. http://dx.doi.org/10.1039/c2jm33762b.
http://dx.doi.org/10.1039/c2jm33762b...
] developed a composite based on BC and type I collagen (COL) and evaluated the in vitro bone regeneration. BC-COL presented a more flexible structure than BC membranes, and showed osteoblastic differentiation that was observed by way of higher levels of alkaline phosphatase activity. Aiming to functionalize BC-COL with other proteins and/or peptides and promote bone formation, the group later synthesized and evaluated in vitro the biomaterial based on BC, COL, apatite (Ap) and OGP or OGP(10-14). The nanocomposites (OGP/OGP(10-14)-BC-COL-Ap) produced did not display cytotoxic, genotoxic or mutagenic action, and in vitro tests showed a synergism between the elements that provided cell growth regarding the BC-Ap nanocomposite. The authors consider that (BC-COL)-Ap associated with OGP peptides might be potential candidates for bone tissue engineering applications .

Recently, Birkheur et al.[181181 Birkheur, S., Faria-Tischer, P. C. de S., Tischer, C. A., Pimentel, E. F., Fronza, M., Endringer, D. C., Butera, A. P., & Ribeiro-Viana, R. M. (2017). Enhancement of fibroblast growing on the mannosylated surface of cellulose membranes. Materials Science and Engineering C, 77, 672-679. http://dx.doi.org/10.1016/j.msec.2017.04.006. PMid:28532078.
http://dx.doi.org/10.1016/j.msec.2017.04...
] prepared aminoaryl mannoside and conjugated it to a succinic group of BC without disrupting the microfibril network. The use of glycoconjugates to BC showed good fibroblast compatibility. Conversely, Souza et al.[182182 Souza, C. F., Lucyszyn, N., Woehl, M. A., Riegel-Vidotti, I. C., Borsali, R., & Sierakowski, M. R. (2013). Property evaluations of dry-cast reconstituted bacterial cellulose/tamarind xyloglucan biocomposites. Carbohydrate Polymers, 93(1), 144-153. http://dx.doi.org/10.1016/j.carbpol.2012.04.062. PMid:23465913.
http://dx.doi.org/10.1016/j.carbpol.2012...
] developed films from mechanical defibrillation of BC followed by the dry-cast generation and incorporation of the xyloglucan (XGT), extracted from tamarind seeds, at various percentages. According to the authors, both mannosylated cellulose[181181 Birkheur, S., Faria-Tischer, P. C. de S., Tischer, C. A., Pimentel, E. F., Fronza, M., Endringer, D. C., Butera, A. P., & Ribeiro-Viana, R. M. (2017). Enhancement of fibroblast growing on the mannosylated surface of cellulose membranes. Materials Science and Engineering C, 77, 672-679. http://dx.doi.org/10.1016/j.msec.2017.04.006. PMid:28532078.
http://dx.doi.org/10.1016/j.msec.2017.04...
] and BC combined with hydrocolloids[182182 Souza, C. F., Lucyszyn, N., Woehl, M. A., Riegel-Vidotti, I. C., Borsali, R., & Sierakowski, M. R. (2013). Property evaluations of dry-cast reconstituted bacterial cellulose/tamarind xyloglucan biocomposites. Carbohydrate Polymers, 93(1), 144-153. http://dx.doi.org/10.1016/j.carbpol.2012.04.062. PMid:23465913.
http://dx.doi.org/10.1016/j.carbpol.2012...
] demonstrated promise as biomaterials for this area.

1.3.4 Bioengineering area

1.3.4.1 World

In bioengineering area, BC has been used mainlny for bioanalysis, enzyme and cell immobilization and to produce biosensors. BC based biosensors have been explored for different applications. These biomaterials have been used in the food and biomedical areas and also to detect contaminants in the environment. Several studies have provided advantageous results to detect contaminants in aqueous matrices, such as bisphenol A in effluent[183183 Li, G., Sun, K., Li, D., Lv, P., Wang, Q., Huang, F., & Wei, Q. (2016). Biosensor based on bacterial cellulose-Au nanoparticles electrode modified with laccase for hydroquinone detection. Colloids and Surfaces. A, Physicochemical and Engineering Aspects, 509, 408-414. http://dx.doi.org/10.1016/j.colsurfa.2016.09.028.
http://dx.doi.org/10.1016/j.colsurfa.201...
] and heavy metal traces as Cd (II) and Pb (II) in drinking water[184184 Qin, D., Hu, X., Dong, Y., Mamat, X., Li, Y., Wågberg, T., & Hu, G. (2018). An electrochemical sensor based on green γ-AlOOH-carbonated bacterial cellulose hybrids for simultaneous determination trace levels of Cd(II) and Pb(II) in drinking water. Journal of the Electrochemical Society, 165(7), B328-B334. http://dx.doi.org/10.1149/2.1321807jes.
http://dx.doi.org/10.1149/2.1321807jes...
]. Pollutant biosensors for detection of H2O2 in the environment[185185 Wang, J., Tavakoli, J., & Tang, Y. (2019). Bacterial cellulose production, properties and applications with different culture methods: a review. Carbohydrate Polymers, 219, 63-76. http://dx.doi.org/10.1016/j.carbpol.2019.05.008. PMid:31151547.
http://dx.doi.org/10.1016/j.carbpol.2019...
] and formaldehyde vapors in houses and workplaces[186186 Hu, W., Chen, S., Liu, L., Ding, B., & Wang, H. (2011). Formaldehyde sensors based on nanofibrous polyethyleneimine/bacterial cellulose membranes coated quartz crystal microbalance. Sensors and Actuators. B, Chemical, 157(2), 554-559. http://dx.doi.org/10.1016/j.snb.2011.05.021.
http://dx.doi.org/10.1016/j.snb.2011.05....
] were also developed showing low detection limits. In foods, BC has been used as an optical sensor for detection and determination of ethylene concentration in fruits[187187 Pirsa, S., & Chavoshizadeh, S. (2018). Design of an optical sensor for ethylene based on nanofiber bacterial cellulose film and its application for determination of banana storage time. Polymers for Advanced Technologies, 29(5), 1385-1393. http://dx.doi.org/10.1002/pat.4250.
http://dx.doi.org/10.1002/pat.4250...
] and potential biosensors for detecting and measuring the growth of pathogenic bacteria[188188 Ghasemi, S., Bari, M. R., Pirsa, S., & Amiri, S. (2020). Use of bacterial cellulose film modified by polypyrrole/TiO2-Ag nanocomposite for detecting and measuring the growth of pathogenic bacteria. Carbohydrate Polymers, 232, 115801. http://dx.doi.org/10.1016/j.carbpol.2019.115801. PMid:31952600.
http://dx.doi.org/10.1016/j.carbpol.2019...
]. Other studies are related to the development of colorimetric pH indicators through the incorporation of anthocyanin from several sources into BC. These indicators demonstrate to be ideal candidates to monitor the freshness/spoilage of foods and beneficial for further development of smart indicator films for practical use[189189 Roy, S., & Rhim, J. W. (2020). Anthocyanin food colorant and its application in pH-responsive color change indicator films. Critical Reviews in Food Science and Nutrition. In press. http://dx.doi.org/10.1080/10408398.2020.1776211. PMid:32543217.
http://dx.doi.org/10.1080/10408398.2020....
].

Many researchers have also applied BC as a carrier of enzymes and cells since the immobilization method provides greater stability, reusability, more tolerance to changes in environmental conditions and less vulnerability to toxic substances present in the surrounding[190190 Żur, J., Piński, A., Michalska, J., Hupert-Kocurek, K., Nowak, A., Wojcieszyńska, D., & Guzik, U. (2020). A whole-cell immobilization system on bacterial cellulose for the paracetamol-degrading Pseudomonas moorei KB4 strain. International Biodeterioration & Biodegradation, 149, 104919. http://dx.doi.org/10.1016/j.ibiod.2020.104919.
http://dx.doi.org/10.1016/j.ibiod.2020.1...
]. In biomedical area, BC based biosensor for dopamine detection in human urine was used successfully[191191 Li, D., Ao, K., Wang, Q., Lv, P., & Wei, Q. (2016). Preparation of Pd/bacterial cellulose hybrid nanofibers for dopamine detection. Molecules, 21(5), 618. http://dx.doi.org/10.3390/molecules21050618. PMid:27187327.
http://dx.doi.org/10.3390/molecules21050...
]. When enzymes such as lysozyme were immobilized onto BC, Bayazidi et al.[192192 Bayazidi, P., Almasi, H., & Asl, A. K. (2018). Immobilization of lysozyme on bacterial cellulose nanofibers: characteristics, antimicrobial activity and morphological properties. International Journal of Biological Macromolecules, 107(Pt B), 2544-2551. http://dx.doi.org/10.1016/j.ijbiomac.2017.10.137. PMid:29079438.
http://dx.doi.org/10.1016/j.ijbiomac.201...
] verified the system obtained good antimicrobial activity against several microorganisms, with potential applications in water treatment or food industry.

Aiming to develop an innovative treatment to remove the paracetamol from wastewater, Żur et al.[190190 Żur, J., Piński, A., Michalska, J., Hupert-Kocurek, K., Nowak, A., Wojcieszyńska, D., & Guzik, U. (2020). A whole-cell immobilization system on bacterial cellulose for the paracetamol-degrading Pseudomonas moorei KB4 strain. International Biodeterioration & Biodegradation, 149, 104919. http://dx.doi.org/10.1016/j.ibiod.2020.104919.
http://dx.doi.org/10.1016/j.ibiod.2020.1...
] immobilized Pseudomonas moorei KB4 onto BC, since this strain is one of the few bacteria able to degrade the analgesic drug. Using the Real-Time PCR technique, they verified that paracetamol exposure influenced the expression of the selected genes encoding the degradation enzymes and KB4 strain was able to degrade 150 mg L-1 of paracetamol in the three cycles. Żywicka et al.[193193 Żywicka, A., Banach, A., Junka, A. F., Drozd, R., & Fijałkowski, K. (2019). Bacterial cellulose as a support for yeast immobilization: correlation between carrier properties and process efficiency. Journal of Biotechnology, 291, 1-6. http://dx.doi.org/10.1016/j.jbiotec.2018.12.010. PMid:30579888.
http://dx.doi.org/10.1016/j.jbiotec.2018...
] immobilized rod-shaped bacteria Lactobacillus delbruecki, spherical-shaped yeast Saccharomyces cerevisiae and hyphae forms of Yarrowia lipolytica) onto BC. As a result, the authors concluded that carrier must be individually combined to the cell type, considering mainly the carrier’s porosity parameter.

1.3.4.2 Brazil

In Brazil, studies in this area still need to be explored. However, recently, Vasconcelos et al.[194194 Vasconcelos, N. F., Cunha, A. P., Ricardo, N. M. P. S., Freire, R. S., Vieira, L., Brígida, A. I. S., Borges, M. F., Rosa, M. F., Vieira, R. S., & Andrade, F. K. (2020). Papain immobilization on heterofunctional membrane bacterial cellulose as a potential strategy for the debridement of skin wounds. International Journal of Biological Macromolecules, 165(Pt B), 3065-3077. http://dx.doi.org/10.1016/j.ijbiomac.2020.10.200. PMid:33127544.
http://dx.doi.org/10.1016/j.ijbiomac.202...
] developed a new process of purification (via alkaline treatment with K2CO3) and chemical modification (NaIO4 oxidation) for covalent immobilization of papain into BC. Oxidized BC (OxBC) demonstrated no cytotoxicity and a greater amount of immobilized enzyme than BC alone, with recovered enzyme activity of 93.1%. The authors immobilized papain in BC by surface response methodology, exhibiting 53% of the generalized papain activity. They concluded that the biomaterial facilitate debridement of skin wounds[195195 Vasconcelos, N. F., Andrade, F. K., Vieira, L., Vieira, R. S., Vaz, J. M., Chevallier, P., Mantovani, D., Borges, M. F., & Rosa, M. F. (2020). Oxidized bacterial cellulose membrane as support for enzyme immobilization: properties and morphological features. Cellulose, 27(6), 3055-3083. http://dx.doi.org/10.1007/s10570-020-02966-5.
http://dx.doi.org/10.1007/s10570-020-029...
].

In another study, Gomes et al.[196196 Gomes, N. O., Carrilho, E., Machado, S. A. S., & Sgobbi, L. F. (2020). Bacterial cellulose-based electrochemical sensing platform: a smart material for miniaturized biosensors. Electrochimica Acta, 349, 136341. http://dx.doi.org/10.1016/j.electacta.2020.136341.
http://dx.doi.org/10.1016/j.electacta.20...
] developed a flexible biosensor for detection of lactate in artificial sweat by immobilizing lactate oxidase (Lox) into BC. The biosensor displayed excellent amperometric response to lactate in artificial sweat, high sensitivity, superior mechanical resistance and biocompatibility; offering new opportunities for the development of wearable devices.

1.3.5 Cosmetics

1.3.5.1 World

In addition to the bioengineering area, scientists have studied the cosmetic application of BC in face masks for delivery of active compounds and increased skin hydration, as well as an emulsion stabilizer[197197 Bianchet, R. T., Vieira Cubas, A. L., Machado, M. M., & Siegel Moecke, E. H. (2020). Applicability of bacterial cellulose in cosmetics: bibliometric review. Biotechnology Reports, 27, e00502. http://dx.doi.org/10.1016/j.btre.2020.e00502. PMid:32695618.
http://dx.doi.org/10.1016/j.btre.2020.e0...
]. In vivo studies conducted by Perugini et al.[198198 Perugini, P., Bleve, M., Redondi, R., Cortinovis, F., & Colpani, A. (2020). In vivo evaluation of the effectiveness of biocellulose facial masks as active delivery systems to skin. Journal of Cosmetic Dermatology, 19(3), 725-735. http://dx.doi.org/10.1111/jocd.13051. PMid:31301106.
http://dx.doi.org/10.1111/jocd.13051...
] demonstrated that BC masks loaded with different bioactive ingredients (peptides, natural extracts and biopolymers) can be used as an effective delivery method for revitalization of facial tissue.

Likewise, Stasiak-Różańska and Płoska[199199 Stasiak-Różańska, L., & Płoska, J. (2018). Study on the use of microbial cellulose as a biocarrier for 1,3-dihydroxy-2-propanone and its potential application in industry. Polymers, 10(4), 438. http://dx.doi.org/10.3390/polym10040438. PMid:30966473.
http://dx.doi.org/10.3390/polym10040438...
] used BC as a biocarrier for 1,3-dihydroxy 2-propanone (DHA) also for cosmetic purposes. The biomaterial showed as an alternative in masking the effects of vitiligo, without leaving unpleasant odor, typical of commercial cosmetics containing DHA. The application of BC is attracting attention of the cosmetics industry and scientific community[197197 Bianchet, R. T., Vieira Cubas, A. L., Machado, M. M., & Siegel Moecke, E. H. (2020). Applicability of bacterial cellulose in cosmetics: bibliometric review. Biotechnology Reports, 27, e00502. http://dx.doi.org/10.1016/j.btre.2020.e00502. PMid:32695618.
http://dx.doi.org/10.1016/j.btre.2020.e0...
] (Table 1).

1.3.5.2 Brazil

In Brazil, as well as in the world, this area has been few explored[200200 Fernandes, I. A. A., Pedro, A. C., Ribeiro, V. R., Bortolini, D. G., Ozaki, M. S. C., Maciel, G. M., & Haminiuk, C. W. I. (2020). Bacterial cellulose: from production optimization to new applications. International Journal of Biological Macromolecules, 164, 2598-2611. http://dx.doi.org/10.1016/j.ijbiomac.2020.07.255. PMid:32750475.
http://dx.doi.org/10.1016/j.ijbiomac.202...
]. BC was successfully loaded with different cosmetic actives for skin treatment and then evaluated through sensorial tests carried out by humans. The sensory tests revealed that masks based on BC were effective for skin adhesion and handling, and the actives improved the skin moisture of the volunteers[201201 Pacheco, G., Mello, C. V., Chiari-Andréo, B. G., Isaac, V. L. B., Ribeiro, S. J. L., Pecoraro, É., & Trovatti, E. (2018). Bacterial cellulose skin masks: properties and sensory tests. Journal of Cosmetic Dermatology, 17(5), 840-847. http://dx.doi.org/10.1111/jocd.12441. PMid:28963772.
http://dx.doi.org/10.1111/jocd.12441...
]. Amorim et al.[114114 Amorim, J. D. P., Souza, K. C., Duarte, C. R., Silva Duarte, I., Ribeiro, F. A. S., Silva, G. S., Farias, P. M. A., Stingl, A., Costa, A. F. S., Vinhas, G. M., & Sarubbo, L. A. (2020). Plant and bacterial nanocellulose: production, properties and applications in medicine, food, cosmetics, electronics and engineering: a review. Environmental Chemistry Letters, 18(3), 851-869. http://dx.doi.org/10.1007/s10311-020-00989-9.
http://dx.doi.org/10.1007/s10311-020-009...
] aiming to develop a biomask that helps in the healing of inflammations caused by acne, loaded BC with natural propolis extract. The dermatological and cosmetic products improved the hydration and texture skin, accelerated the healing process and improved the self-esteem of acne patients.

2. Conclusions

BC stands out as a versatile biomaterial that allows promising applications in the areas of food, electronics, bioengineering, cosmetics and biomedics. In Brazil, the areas of food, bioengeering and cosmectics are still scarce for economic reasons. In the food field, Brazilian studies are essentially focused on the development of food packaging. Although a large amount of research have been developed worldwide in the electronic/ electrochemical/ magnetic fields, in Brazil, research in this area has only started to be more explored recently. Certainly, the most significant contributions of Brazilian researchers using BC have been made in the biomedical area. We highlight here the use of BC to treat psoriasis and cutaneous leishmaniasis, and the development of sensors in the clinical diagnosis of dengue. In addition, the incorporation of antimicrobials, polysaccharides, proteins / peptides and other compounds into BC has shown promising results in wound healing properties. In tissue engineering and regenerative medicine, the immobilization of biomolecules and their potential in vitro and in vivo is still being explored for greater activity and stability. In conclusion, Brazil is one of the countries that most develops research using BC. However, the expansion of the use and commercialization of BC products could be increased through improvements in its productivity, using, for example, residues generated in Brazilian agribusiness, which could contribute to an environmentally friendly society. Studies with new methods and technologies for the production of cellulose need to be explored, in addition to new biochemical and genetic investigations. Greater government financial support for Brazilian research is also sorely needed.

3. Acknowledgements

The authors would like to thank the Universidade Estadual de Londrina, the Instituto Federal do Paraná, the Universidade de Araraquara, the Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES. H. S. Barud thanks CNPq (Grant No. 407822/2018-6; INCT-INFO), São Paulo Research Foundation (FAPESP) (Grants no. 2018/25512-8 and no. 2013/07793-6), and TA Instruments Brazil.

  • How to cite: Marestoni, L. D., Barud, H. S., Gomes, R. J., Catarino, R. P. F., Hata, N. N. Y., Ressutte, J. B., & Spinosa, W. A. (2020). Commercial and potential applications of bacterial cellulose in Brazil: ten years review. Polímeros: Ciência e Tecnologia, 30(4), e2020047. https://doi.org/10.1590/0104-1428.09420

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Publication Dates

  • Publication in this collection
    23 Apr 2021
  • Date of issue
    2020

History

  • Received
    15 Oct 2020
  • Reviewed
    04 Jan 2021
  • Accepted
    05 Jan 2021
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