MINI-REVIEW Bacterial nanocellulose production and application: a 10-year overview Angela Faustino Jozala1 & Leticia Celia de Lencastre-Novaes2 & André Moreni Lopes3 & Valéria de Carvalho Santos-Ebinuma4 & Priscila Gava Mazzola2 & Adalberto Pessoa-Jr3 & Denise Grotto1 & Marli Gerenutti1 & Marco Vinicius Chaud1 Received: 3 September 2015 /Revised: 7 December 2015 /Accepted: 9 December 2015 /Published online: 8 January 2016 # Springer-Verlag Berlin Heidelberg 2016 Abstract Production of bacterial nanocellulose (BNC) is be- coming increasingly popular owing to its environmentally friendly properties. Based on this benefit of BNC production, researchers have also begun to examine the capacity for cel- lulose production through microbial hosts. Indeed, several re- search groups have developed processes for BNC production, and many studies have been published to date, with the goal of developing methods for large-scale production. During BNC bioproduction, the culture medium represents approximately 30 % of the total cost. Therefore, one important and challeng- ing aspect of the fermentation process is identification of a new cost-effective culture medium that can facilitate the pro- duction of high yields within short periods of time, thereby improving BNC production and permitting application of BNC in the biotechnological, medical, pharmaceutical, and food industries. In this review, we addressed different aspects of BNC production, including types of fermentation processes and culture media, with the aim of demonstrating the impor- tance of these parameters. Keywords Bacterial nanocellulose . Biopolymers . Biomaterial . Bioprocess . Bioproducts . Fermentation process .Gluconacetobacter xylinus Introduction Ten years of advances in biopolymer research have demon- strated the importance and potential of biopolymers for a va- riety of applications, particularly for biopolymers produced by microorganisms, including bacterial nanocellulose (BNC). Many types of BNCs have been developed for various appli- cations, including tissue regeneration, drug delivery systems, vascular grafts, and scaffolds for tissue engineering in vitro and in vivo (Czaja et al. 2007; de Azeredo 2013; Almeida et al. 2014; Oliveira Barud et al. 2015; Martínez-Sanz et al. 2016). Depending on the purpose of the application, BNC can provide improved mechanical qualities to the biomaterial ow- ing to its biocompatibility, biofunctionality, lack of toxicity, and ease of sterilization (Klemm et al. 2011). For this reason, there are currently several methodologies for large-scale pro- duction of BNC. Researchers have focused on improving the efficiency of the production process, resulting in satisfactory yields that are compatible with the demand for this type of cellulose (Lin et al. 2014; Zhang et al. 2014; Cakar et al. 2014; Li et al. 2015). The culture medium is the most important factor for the total cost of production of BNC. Therefore, one important aspect in BNC production is to identify a low-cost culture medium that can improve the yield of BNC and be used as an economically viable solution for application in a range of fields (Cakar et al. 2014; Padmanaban et al. 2015). Therefore, the aim of this review is to discuss advance- ments in BNC production within the last 10 years. To this * Angela Faustino Jozala angela.jozala@prof.uniso.br 1 Department of Technological and Environmental Processes, Universidade de Sorocaba – UNISO, Sorocaba, SP, Brazil 2 Faculty of Pharmaceutical Sciences, Universidade de Campinas, UNICAMP, Campinas, Brazil 3 Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, USP, São Paulo, Brazil 4 Department of Bioprocess and Biotechnology, School of Pharmaceutical Sciences, Universidade Estadual Paulista – UNESP, Araraquara, SP, Brazil Appl Microbiol Biotechnol (2016) 100:2063–2072 DOI 10.1007/s00253-015-7243-4 http://crossmark.crossref.org/dialog/?doi=10.1007/s00253-015-7243-4&domain=pdf end, we will describe the types of processes and culture media used for BNC production. We also discuss the potential appli- cations of BNC. Cellulose Cellulose is the most common natural polymer world- wide. According to a worldwide estimate, 1014 t of cellu- lose pulp are produced each year, emphasizing the eco- nomic importance of this polymer (Donini et al. 2010; Lin et al. 2014). Due to the presence of components other than cellulose, different chemical treatments employing highly polluting chemical products, such as chlorine gas, caustic soda, carbon disulfide, carbon monoxide, and car- bon dioxide, are often needed prior to use in order to obtain pure cellulose (Basta and El-Saied 2009; Klemm et al. 2011). Donini et al. (2010) compared the productivity of cellulose from plants and microorganisms in order to determine the advantages of producing cellulose from microorganisms. In their analysis, they compared the production of cellulose from 1 ha of eucalyptus with a mean annual increment (MAI) of 50 m3, providing a basic density of 500 kg/m3; this generated an MAI of 25 t/ha/year. With 7 years from planting to culti- vation, yielding about 45 % cellulose contents, this process would yield about 80 t of cellulose/ha after 7 years of cultiva- tion. The authors found that the same production could be achieved with bacteria to a hypothetical yield of 15 g/L in 50 h of culture (average of 0.3 g/h) in a bioreactor of 500 m3 in approximately 22 days. This more efficient production method also yielded pure and ecologically sustainable BNC as the product. Unlike plant cellulose, BNC is produced in the pure form, devoid of lignin, hemicellulose, pectin, or any other compound present in the plant pulp and does not contain components of animal origin. In addition, it has superior mechanical properties compared with plant cellulose (Fu et al. 2013). The anhydroglucose units and various bacterial cellulose fibrils interact closely with each other to form a crystalline structure through internal and external hydrogen bonds, resulting in the compaction of fibers that are completely insol- uble in water but that can be hydrated (Lynd et al. 2002; Conley et al. 2016) The thin nanofibers have a diameter of 20–100 nm, with a large surface area per unit; this feature, combined with the hydrophilic nature of BNC, results in high water absorption capacity, better adherence, and increased moisture content (Fu et al. 2013; Numata et al. 2015b). These properties, combined with the distinct physical and mechani- cal properties of the molecule, including its insolubility, rapid biodegradability, tensile strength, elasticity, durability, and nontoxic and nonallergenic features, make BNC ideal for the production of several products with high added value, such as artificial skin used as a temporary substitute in the treatment of burns and other dermal injuries (Thompson and Hamilton 2001; Rehim et al. 2014; Cakar et al. 2014). BNC is a highly crystalline linear polymer of glucose syn- thesized mainly by the bacterium Gluconacetobacter xylinus (formerly named Acetobacter xylinus). Although BNC pro- duction has been studied primarily in G. xylinus, other micro- organisms also exhibit the ability to synthesize this biopoly- mer, such as other species of Gluconacetobacter, Agrobacterium tumefaciens, Rhizobium spp., and Gram- positive Sarcina ventriculli (Tanskul et al. 2013; Mohammadkazemi et al. 2015). G. xylinus is the primary microbial producer of BNC and has become a model system for the study of the biosyn- thetic mechanisms of BNC in bacteria (Keshk 2014). For cellulose production, G. xylinus builds a nanofibrilar film with a denser lateral surface and a gelatinous layer on the opposite side (Kurosumi et al. 2009; Cai and Kim 2009). The biochemical process of cellulose synthesis by G. xylinus consists of three main steps: (i) polymerization of glucose residues in β-1-4 glucan, (ii) extracellular secre- tion of linear chains, and (iii) organization and crystalliza- tion of glucan chains through hydrogen bonds and van der Waals forces arrayed in a hierarchy into strips. Thus, microfibril cellulose is produced (Donini et al. 2010; Klemm et al. 2011). Despite the above studies, the metabolic pathways through which microorganisms regulate BNC production remain un- clear. Moreover, it is still necessary to identify new microor- ganisms that can produce this biopolymer. Biotechnology-based production of BNC The production of environmentally friendly products is becoming increasingly important; in this context, the pro- duction of nanocellulose through microbial pathways is advantageous. Indeed, BNC production using microor- ganisms is industrially important because such microor- ganisms exhibit rapid growth, allowing for high yields and year-round availability of product (Santos-Ebinuma et al. 2013). There are two main methods for producing BNC using microorganisms: static culture, which results in the accumula- tion of a thick, leather-like white BC pellicle at the air-liquid interface (Kuo et al. 2015), and stirred culture, in which cel- lulose is synthesized in a dispersed manner in the culture me- dium, forming irregular pellets or suspended fibers (Krystynowicz et al. 2002; Czaja et al. 2004). The choice between these two types of production (i.e., static or stirred culture) depends on the final application of BNC since the morphological, physical, and mechanical properties of the 2064 Appl Microbiol Biotechnol (2016) 100:2063–2072 formed polymer vary according to the method of cultivation. For example, cellulose produced by stirred culture has low mechanical strength compared with that produced by static culture. Moreover, stirred culture results in lower yields than static cultures and a higher probability of mutations in the microorganism, which may affect the production if BNC. On the other hand, static culture requires a larger cultivation area and a longer culture time (Chawla et al. 2009; Keshk 2014; Cakar et al. 2014; Lee et al. 2014; Jeon et al. 2014; Tyagi and Suresh 2015). Some considerations must be taken into account when de- termining the conditions necessary to produce BNC. The cost- benefit from the culture medium in terms of yield of BNC is an important factor, and therefore, the composition and vol- ume of the medium should be considered. The composition of the culture medium can directly affect the profitability of the biotechnological process and is therefore critical for the pro- duction of any bioproduct, including BNC (Ruka et al. 2012; Lee et al. 2014; Mohammadkazemi et al. 2015). The fermentation medium must contain, at minimum, a carbon source, a nitrogen source, and other macro- and micronutrients required for the growth of the microorganism, such as phosphorus, sulfur, potassium, and magnesium salts (Krystynowicz et al . 2002; Chawla et al . 2009; Mohammadkazemi et al. 2015). The synthesis of cellulose is susceptible to chemical agents and the physical influence of the compounds present during its production. Thus, regardless of the method of production, factors such as yield, morphology, structure, and physical properties may be affected by the culture medium used (Jung et al. 2010; Ruka et al. 2012; Mohammadkazemi et al. 2015). The culture medium typically used for the production of BNC, regardless of the use of static or stirring culture, was first described in 1954 by Hestrin and Schramm (HS) (Schramm and Hestrin 1954). This medium is composed of 2 % glucose (the major carbon source), 0.5 % peptone, 0.5 % yeast extract, 0.27 % of anhydrous disodium phosphate, and 0.15 % citric acid monohydrate. However, HS medium can increase the final production cost of the biopolymer and is considered unfeasible for commercial production of BNC due to its high cost (Tyagi and Suresh 2015; Huang et al. 2016). For this reason, various studies have been performed over the last 10 years to improve BNC production based on several fermentation parameters, such as pH control, and al- ternative carbon sources, including sugar cane, molasses, su- crose, and rotten fruit, as well as culture in a static and agitated environment (Table 1). Gluconacetobacter can use several carbon sources to syn- thesize BNC. Glucose is the most often used because it is both an energy source and the ideal precursor for obtaining cellu- lose during the biosynthesis process. However, BNC yield may be low because of the presence of glucose dehydrogenase, which converts glucose into gluconic acid, thereby decreasing the pH of the culture and potentially af- fecting BNC biosynthesis, is present in the cell membrane of G. xylinus (Kuo et al. 2015)). Beginning in 2006, Keshk and Sameshima studied the use of HS culture medium alone and in the presence of 1 % lig- nosulfonate (HSL) in six strains of G. xylinus (G. xylinus IFO 13693, 13,772, 13,773, 14,815, and 15,237) in static culture to produce BNC. The strains G. xylinus IFO 13693 and 13,773 exhibited the highest BNC production in HSL (around 16.32 g/L for both strains), which was higher than that obtain- ed in HS (close to 7.92 g/L). According to the authors, the presence of lignosulfonate promotes an increase in BNC production due to the inhibition of gluconic acid formation in the presence of antioxidant poly- phenolic compounds in the lignosulfonate. In experiments performed with lignosulfonate, the pH was closer to 4.0 for all strains, whereas under other conditions, the final pH was around 3.0, which could be explained by gluconic acid pro- duction. Furthermore, FT-IR results showed that the BNC produced in the presence of lignosulfonate displayed a higher crystallinity index and Iα-rich cellulose. In 2009, Mikkelsen and coworkers studied the production of BNC by G. xylinus ATCC 53524 under static culture con- ditions using modified HS medium by replacing glucose with different carbon sources, i.e., mannitol, glycerol, fructose, su- crose, and galactose. Sucrose and glycerol showed the highest cellulose yields of 3.83 and 3.75 g/L, respectively, after 96 h of fermentation, whereas mannitol, fructose, and glucose (in the original HS medium) resulted in yields below 2.5 g/L. Cross-polarization/magic angle spinning (CP/MAS) 13C- NMR spectroscopy showed that irrespective of the carbon source used, the cellulose produced by was pure and crystal- line. These findings demonstrate the ability of G. xylinus to metabolize different sources of carbon to produce BNC. Ac- cording to the authors, although the rate and extent of cellu- lose production was characteristic for the carbon source, the microscopic and molecular organization of cellulose produced was highly conserved, suggesting that differences in produc- tivity due to the carbon source were due to substrate limita- tions, rather than changes in polymerization. In the same year, Kurosumi and collaborators reported the production of cellulose by Acetobacter xylinum NBRC 13693 using juices (orange, apple, pineapple, Japanese pear, and grape) as culture media. The authors evaluated different con- ditions for these juices: fruit juice adjusted pH 6 with a nitro- gen source of HS medium (medium I), fruit juice adjusted to pH 6 (medium II), and sugar reagents (glucose, fructose, and sucrose) with a nitrogen source in HS medium (medium III). The content and type of sugar present in each fruit juice var- ied, and the authors suggested that appreciable amounts of the bacterial cellulose could be produced from fruit juices contain- ing an abundance of sucrose and fructose. The authors found a Appl Microbiol Biotechnol (2016) 100:2063–2072 2065 higher cellulose yield (5.9 g/L) in culture medium containing orange juice supplemented with a nitrogen source after 96 h of bioprocessing. The BNC produced from this experiment was not characterized; therefore, it is not possible to determine whether the sugars present in different fruit juices generated BNC molecules with differential characteristics. Jung et al. (2010) employed molasses and corn steep liquor to reduce the cost of the culture media in stirred culture. The authors found that the final pH in the presence of molasses was around 5.0 under several conditions, resulting in reduced production of gluconic acid because molasses components have lower amounts of glucose. The authors also evaluated whether the presence of organic acids (i.e., acetic acid, citric acid, lactic acid, pyruvic acid, and malic acid) would promote an increase in BNC biosynthesis. As result, the presence of acetic acid generated the highest yield (3.12 g/L). Moreover, FT-IR spectra of the BNC produced from the molasses and complex media showed similarities, indicating that the micro- organisms could metabolize different carbon sources, produc- ing BNC with the same characteristics. Trovatti et al. (2011) first reported the production of BNC byGluconacetobacter sacchari, isolated from Kombucha tea. The strain harvested in HS medium containing glucose, su- crose, fructose, mannitol, or glycerol as the carbon source yielded the highest cellulose production (2.7 g/L in 96 h) when glucose was the carbon source. This value was consis- tent with that obtained from other cellulose-producing strains, and the structure of the cellulosic matrix obtained was identi- cal to that produced by other bacteria. Lu et al. (2011) studied the effects of six different alcohols (methanol, ethylene glycol, n-propanol, glycerol, n-butanol, and mannitol) added in the HS medium on cellulose produc- tion by strain A. xylinum 186 in static culture at 30 °C for 6 days. Interestingly, the addition of 1 % methanol produced a yield of 1.04 g/L, whereas the addition of 0.5 % ethylene glycol, n-propanol, or n-butanol produced yields of 1.06, 0.96, and 1.33 g/L BNC, respectively. The use of 3 % glycerol yielded 1.08 g/L BNC, and the addition of 4 % mannitol yielded 1.25 g/L BNC. Therefore, alcohols could be classified (in order from highest to lowest) based on BNC yield, as follows: n-butanol > mannitol > glycerol > ethylene glycol > methanol > n-propanol. Wu and Liu (2012) studied HS broth supplemented with thin stillage (TS), which is the liquid portion of distillery Table 1 Conditions, yields, production methods and microorganisms used to produce bacterial nanocellulose described in the literature starting in 2006 Carbon source BNC Yield (g/L) Production method Microorganism Reference HS in the presence of 1 % lignosulfonate 16.32 Static culture at 28 °C for 168 h G. xylinus IFO 13693 (Keshk and Sameshima 2006) Sucrose 3.83 Static culture at 30 °C for 96 h G. xylinus ATCC 53524 (Mikkelsen et al. 2009) Orange juice containing nitrogen sources of HS 5.90 Static culture at 30 °C for 96 h Acetobacter xylinum NBRC 13693 (Kurosumi et al. 2009) Glucose in the presence of MCP-1 1.20 Stirred culture at 30 °C and 125 rpm for 288 h Acetobacter xylinum JCM 9730 (Hu and Catchmark 2010) Molasses and corn steep liquor in the presence of acetic acid 3.12 Stirred culture at 30 °C and 200 rpm for 168 h Acetobacter sp. V6 (Jung et al. 2010)) Glucose 2.70 Static culture at 30 °C for 96 h G. sacchari (Trovatti et al. 2011)) Glucose (HS broth supplemented with n- butanol) 1.33 Static culture at 30 °C for 144 h A. xylinum 186 (Lu et al. 2011) HS broth supplemented with thin stillage 10.22 Static culture at 30 °C for 168 h G. xylinus (BCRC 12334) (Wu and Liu 2012) Industrial residues from olive oil production 1.28 - G. sacchari Gomes et al. (Gomes et al. 2013) Molasses 1.64 Static semicontinuous process for 168 h G. xylinus (FC01) Çakar et al. (Cakar et al. 2014) Waste beer yeast treated with ultrasonication 7.02 Stirred culture at 30 °C and 150 rpm G. hansenii CGMCC 3917 Lin et al. (Lin et al. 2014) Rotten fruit culture 60 Static culture at 30 °C and 96 h G. xylinus ATCC 53582 (Jozala et al. 2015)) Wood hot water extract 0.15 Static culture at 28 °C for 672 h Acetobacter xylinum 23,769 (Erbas Kiziltas et al. 2015b) Waste water of candied jujube hydrolysate 2.25 Static culture at 30 °C for 144 h G. xylinus CGMCC 2955 (Li et al. 2015) Citrus Juice and sucrose – Static culture at 30 °C G. sp. gel_SEA623-2 (Kim et al. 2015) Lipid fermentation wastewater 0.66 Static culture at 28 °C for 5 days G. xylinus CH001 (Huang et al. 2016) HS Hestrin-Schramm culture medium, MCP-1 methylcyclopropane-1 2066 Appl Microbiol Biotechnol (2016) 100:2063–2072 stillage from the fermentation of grain-based feedstock rich in organic acids and amino acids. The authors observed that complete replacement of glucose with TS enhanced the pro- duction of BNC, achieving a BNC yield of 10.22 g/L under conditions in which the TS was 100 % after 7 days of culti- vation. According to the authors because TS is rich in organic acids, it could support the growth of G. xylinus, and the glu- cose in HS medium could be employed for BC biosynthesis. Therefore, the production of gluconic acid was low, promot- ing the highest production of BNC. Gomes et al. (2013) studied the production of BNC by G. sacchari using industrial residues from olive oil (DOR) as nutrients and a carbon source. BNC production without the addition of any nutrients was around 0.80 g/L after 96 h of incubation, whereas conventional HS medium produced around 2.5 g/L BNC. Supplementation with olive oil residues containing nitrogen and phosphate sources [(NH4)2SO4 and KH2PO4, respectively] resulted in a 2-fold increase in BNC production compared with unsupplemented medium. The BNC produced employing DOR as carbon source exhibited a typical homogeneous three-dimensional network of nano- and microfibrils of cellulose, as previously reported for BNC. Çakar et al. (2014) evaluated the production of cellulose using a static semicontinuous process in molasses medium. The authors achieved a maximum cellulose yield (1.64 g/L) when using a molasses ratio of 1:2 for 7 days. The use of molasses as a carbon source produced BNCwith structure that changed from thin fibrils to a web-like pattern according to the incubation period. However, in general, the BNC produced exhibited a dense fibril structure. Lin et al. (2014) used waste beer yeast (WBY) to improve BNC production by Gluconacetobacter hansenii CGMCC 3917. WBY hydrolysates, treated with ultrasonication, exhib- ited a high cellulose yield (7.02 g/L), almost 6-fold higher than that from untreated WBY (1.21 g/L). This result can be ex- plained by the fact that the uncentrifuged samples after pre- treatment had a high sugar concentration (and showed the highest sugar yields), which could inhibit BNC production and reduce the supply of oxygen by the liquid medium. The properties and microstructure of BNC produced by WBY hy- drolysates were as good as those obtained from the conven- tionally used chemical media. Jozala et al. (2015) evaluated HS broth, milk whey, rotten fruit (plums, green grapes, pineapples, and apples) and com- bined milk whey/rotten fruit at different proportions as alter- native sources to produce BNC by G. xylinus ATCC 53582 at 30 °C in a static culture for 0, 24, 48, 72, or 96 h. The highest production was observed after 96 h of bioprocessing using rotten fruit as main carbon source. The production achieved with this alternative medium was higher than obtained with HS medium (standard medium) and those reported in several previous reports. Figure 1 shows BNC produced by culture medium containing rotten fruits. Li et al. (2015) studied the use of wastewater of candied jujube (WWCJ) forG. xylinus CGMCCNo. 2955 under static culture to obtain BNC. According to the authors, WWCJ containedmainly glucose, glucan, and very low levels of other carbohydrates, providing an interesting carbon source with which to obtain BNC. WWCJ was used in three different conditions, namely WWCJ media containing ammonium cit- rate, sodium dihydrogen phosphate, and calcium carbonate, WWCJ without ammonium citrate, and WWCJ hydrolysate at 80 °C. The bioprocess took 6 days and promoted the pro- duction of BNC in all conditions analyzed. However, the WWCJwithout ammonium citrate media generated the lowest BNC yield (0.25 g/L), indicating that ammonium citrate could be a key factor for BNC production. With WWCJ and the hydrolysate, the BNC yields were 1.50 and 2.25 g/L, respectively. Kim et al. (2015) isolated a new BCN-producing strain identified as G. sp. gel_SEA623-2 from citrus fruit juice. The authors evaluated BNC production through five fruit juices, including orange, grape, apple, and pear juices, at sev- eral pH values (2.0, 2.5, 3.0, 3.5, 4.0, and 5.0), temperatures (20, 30, 35, and 40 °C), and brix values (5, 10, 20, and 30) during static culture. Among the fruit juice sources examined, Fig. 1 Bacterial Nanocellulose produced by culture medium composed by rotten fruits. AAfter tretatment with NaOH; B1, B2 size and thikness, C transparency. (source: personal files) Appl Microbiol Biotechnol (2016) 100:2063–2072 2067 unshu juice was the most favorable for BNC production byG. sp. gel_SEA623-2, showing that this bacteria had a high pro- ductive capacity in a citrus processing medium. The optimum pH and temperature for BNC production were 3.5 and 30 °C, respectively. Erbas Kiziltas et al. (2015b)evaluated wood hot water ex- tract (HWE), a residual material originating from pulp mills and lignocellulosic biorefineries for the production of BNC using A. xylinum 23,769. This source had mainly monomeric sugars, organic acids, and organics compounds. The cultiva- tion was performed under static culture by varying the pH range from 5 to 8 and temperature range from 26 to 30 °C for BC production from A. xylinum 23,769 in HWE. Although an acidic pH generally promotes high BNC production, the authors found that the maximum production of BNC (0.15 g/ L) was achieved at a pH of 8 and a temperature of 28 °C. In addition, the results achieved by the authors showed that the fractured surface morphology of the BNC pellicles fromwood HWE exhibited a smaller cellulose fibril diameter compared with the BC pellicles from the HS medium. Kuo et al. (2015) evaluated the effects of 100 mM acetate buffered at different pH on BNC production by static cultiva- tion of G. xylinus. After 8 days of cultivation, the maximum amount of BNC produced was 2.98 g/L when 20 g/L glucose was employed in 100 mM acetate-buffered medium at pH 4.75. In contrast, the BC produced in yeast extract- peptone-dextrose broth (YPD) and HS media was only 0.66 and 1.23 g/L, respectively. The final pH of acetate-buffered medium (buffered at pH 4.75, 5.50, and 6.00) was close to its initial value. However, the final pH of YPD and HS media was lower than 3.5. Acetate-buffered medium can maintain a pH environment suitable for BC biosynthesis for a longer time as compared with traditional unbuffered HS medium. These results clearly showed the effects of pH on BNC production. Huang and co-authors (2016) were the first to use lipid fermentation wastewater (fermentation broth after separation with yeast biomass) as a substrate for BNC production by G. xylinus. The chemical oxygen demand (COD) value of lipid fermentation wastewater was 25.59 mg/L, which could result in low BNC yield. According to the authors, the pretreatment of lipid fermentation wastewater to hydrolyze the extracellular polysaccharides may make the wastewater more biodegrad- able and could improve BNC production by reducing the pro- duction cost of BNC. Moreover, the lipid fermentation waste- water environment had only minor effects on the structure of BNC. During the last 10 years, several groups have tested alter- native carbon sources aiming to increase BNC yields and de- crease production costs (Table 1). Carbon sources with low sugar contents have generated interesting results. Although the use of alternative carbon sources can improve BNC pro- duction, it is also necessary to control the environmental con- ditions, such as pH and temperature. Temperature is a crucial factor that affects the growth of microorganisms, thereby influencing cellulose production. In addition to temperature and pH, the dissolved oxygen concentration in the culture medium is an important factor that can affect the production of cellulose. In static cultures, the substrate must be transported entirely by diffusion, and be- cause the carbon sources are generally available, the low availability of oxygen can become the limiting factor for cell metabolism and can have a negative effect on cellulose pro- duction and quality (Chawla et al. 2009). Ruka and collaborators (2012) found that the production of cellulose increases as the surface area of static medium and medium volume increase; however, this enhanced yield is also associ- ated with increased cost and production time. During the biosynthesis of BNC, if the culture broth con- tains different components, such as organic, inorganic, or polymeric materials, these components can be incorporated into the membrane of BNC, promoting the functionalization of BNC. There are two basic synthetic approaches for creating BNC matrix composites: in situ and ex situ. In the in situ method, secondary components can be introduced into the BNC culture media at the beginning of the BNC synthesis process. For the ex situ method, secondary components can be introduced into the BNC matrix by the solution impregna- tion method (Erbas Kiziltas et al. 2015a). The effects of chondroitin sulfate and hyaluronic acid in bacterial cellulose production were studied by Molina de Olyveira et al. (2013). The authors analyzed BNC production using transmission infrared spectroscopy (FTIR), X-ray dif- fraction (XRD), and scanning electron microscopy (SEM). FTIR analysis showed an interaction between bacterial cellu- lose nanobiocomposites and calcium phosphate. Thus, the ad- dition of different compounds in the culture medium can di- rect the formation of bacterial cellulose with specific characteristics. Kiziltas et al. (2015b) studied the biosynthesis of BNC by A. xylinum 23,769 in the presence of different nanoparticles (cellulose nanofibrils [CNFs], exfoliated graphite nanoplatelets [xGnPs], and nanoclay [NC]) using an in situ approach. All BC-based nanomaterials produced exhibited good dispersion of the NPs within the BC matrix, and the NPs were found embedded among the voids and microfibrils. The thermal stability and residual mass of BNC-xGnP and BNC-NC nanomaterials were significantly increased com- pared with that of pure BNC. CNF incorporation into the BNC matrix did not change the thermal stability and residual mass of the BNC matrix. The cultivation method is also an important parameter that should be analyzed in greater detail. Static culture is the most commonly usedmethod; however, many bioreactors contain a stirred tank, conventional airlift, and modified airlift with a rectangular wire-mesh draft tube. The BNC obtained from these types of bioreactors is fibrous or in pellet form 2068 Appl Microbiol Biotechnol (2016) 100:2063–2072 (Kralisch et al. 2010; Lee et al. 2014; Wu and Li, 2015), and this technology may generate promising results. Therefore, further studies are needed to examine BNC functionalization during its biosynthesis, which may be a key factor to promote the market expansion of this biomaterial. Applications of BNC Based on the properties of BNC, including its high purity, high degree of crystallinity, high density, good shape retention, high water-binding capacity, and higher surface area as com- pared to native cellulose, BNC may have applications in a variety of contexts, such as the textile industry, nonwoven cloth, paper, food, pharmaceuticals, waste treatment, broad- casting, mining, and refineries (Table 2) (Wu and Liu 2012; Ashjaran et al. 2013; Lin and Dufresne, 2014). These distinc- tive properties have facilitated the use of BNC in the fabrica- tion of several different products, including tires, headphone membranes, high performance speaker diaphragms, high- grade paper, make-up pads, diet foods, and textiles (Shah et al. 2013). Fragmented BNC has potential applications in paper- making, allowing the production of flexible/durable paper and paper with high filler content, which is ideal for bank- note paper (Chawla et al. 2009; Ashjaran et al. 2013), and its use as a binding agent in papermaking has been inves- tigated (Basta and El-Saied 2009). Mautner et al. (2015) demonstrated that BNC-based nanopaper was suitable for tight ultrafiltration operations, while Li et al. (2015) de- veloped a low-cost and environmentally friendly paper- based energy-storage device using bacterial cellulose– polypyrrole nanofibers in combination with multiwalled carbon. Chemically pure cellulose can be used in processed foods as a thickening and stabilizing agent or for the pro- motion of gelling and water binding. Moreover, BNC is a type of dietary fiber and has been classified as a Bgenerally recognized as safe^ (GRAS) food, approved for marketing by the US Food and Drug Administration (FDA) in 1992 (Shi et al. 2014). The first use of BNC in the food industry was in BNata^ in the Philippines; Nata is made from a BNC gel and is a traditional dessert in Southeast Asia (Chawla et al. 2009; Shi et al. 2014). There are many types of Nata, including Nata de coco and Nata de pina, and the flavors of these products are controlled by the culture medium source. For example, Nata de coco uses coconut as the source, whereas Nata de Pina uses pineapple as the source (Shi et al. 2014). Cellulose-producing microorganisms can be grown in cul- ture medium sources, such as fruit syrup, that allow the pro- duced cellulose to acquire the nature flavor and pigment of the fruit. Moreover, BNC can be produced to have a variety of shapes and textures, giving BNC many different applications in foods (Shi et al. 2014). Owing to its unique nanoscaled 3D network structure, BNC can serve as a natural scaffold material for the regener- ation of a wide variety of tissues (Fu et al. 2013). The most exciting applications of this biomaterial are in the biomedical field, where BNCs have been used as wound dressing mate- rials, artificial skin, vascular grafts, scaffolds for tissue engi- neering, artificial blood vessels, medical pads, and dental im- plants (Shah et al. 2013). The many advantages of BNC, in- cluding its biocompatibility, conformability, elasticity, trans- parency, ability tomaintain a moist environment in the wound, and ability to absorb exudates during the inflammatory phase, provide great potential for applications in wound healing sys- tems. A thorough review of the most recent developments in Table 2 Bacterial nanocellulose applications in different areas Area Application Cosmetics Stabilizer of emulsions like creams, tonics, conditioners, nail polishes. Textile industry Sports clothing, tents and camping equipment Mining and refinery Sponges to collect leaking oil, materials for absorbing toxins. Waste treatment Recycling of minerals and oils Sewage purification Urban sewage purification, ultra filtration water Communications Diaphragms for microphones and stereo headphones Food industry Edible cellulose (nata de coco) Paper industry Artificial replacement of wood, special papers Medicine/ biomedical Temporary artificial skin for burns and ulcers, dental implant components; Antimicrobial wound dressing, Nanofilm, Drug Delivery, Drug excipient. Laboratories Protein immobilization, chromatographic techniques, tissue culture medium Electronics Opto-electronics materials (liquid crystal displays) Energy Membrane fuel cell (palladium) Appl Microbiol Biotechnol (2016) 100:2063–2072 2069 BNC-based skin tissue repair materials was published by Chawla et al. (2009). Besides improving the existing properties of BNC, com- posite materials have imparted BNC with new features displayed by typical inorganic or organic nanomaterials; these features include antibacterial effects; optical, electrical, and magnetic properties and catalytic and biomedical activities (Hu et al. 2014). For example, Shah et al. (2013) reviewed the applications of BNC composites in biomedical products, conducting materials, electrical devices, separation and waste purification, and composites with high mechanical strength for industrial applications. Additionally, Hu et al. (2014) reviewed the potential advantages and different applications of BNC-based functional nanomaterials, focusing mainly on application as sensors, photocatalytic nanomaterials, optoelec- tronic materials and devices, and magnetically responsive membranes. The architecture of BNC materials can be engineered over length scales ranging from nano- to macro-sized by control- ling the biofabrication process. Additionally, surface modifi- cations have a vital role in determining the in vivo perfor- mance of biomaterials. Molina de Olyveira et al. (2013) stud- ied the potential of gamma irradiation treatment for the mod- ification of the surface properties of BNC, enhancing its po- tential for biomedical applications. Samples did not show sig- nificant variations in thermal properties; however, a higher pore density was produced in irradiated samples than in non- irradiated samples, resulting in slower diffusion than that ob- served in nonirradiated membranes. BNC has a potential role in drug delivery systems. Müller et al. (2013) studied the applicability of BNC as a drug deliv- ery system for proteins using serum albumin as a model drug. They found that freeze-dried samples showed lower uptake capacity for albumin than native BNC, which could be ex- plained by changes in the fiber network during the freeze- drying process. The integrity and biological activity of proteins could be retained during the loading and release processes. Rajwade et al. (2015) recently published a review of the applications of BNC in the biomedical field, such as scaffolds, carriers for drug delivery, and wound-dressing ma- terials. Numata et al. (2015a) studied the combination BNC gel and amphiphilic block copolymer nanoparticles as a drug delivery system, and Cacicedo et al. (2015) created a hybrid microparticle system utilizing BNC and stereospecific nucle- ation of mesoporous hybrid microspheres composed of CaCO3. This hybrid system can be potentially used as an implantable drug delivery system for personalized oncological therapies. Through enzymatic or acidic hydrolysis, BNC can form cellulose nanocrystals (NCCs), cellulose acicular particles with high crystallinity and with widths and lengths of 5– 70 nm and between 100 nm and several micrometers, respec- tively (Klemm et al. 2011). NCCs also have many beneficial properties, including biocompatibility, biodegradability, and a lack of toxicity, making NCCs an excellent candidate for phar- maceutical applications. Owing to its negative change and large surface area, abundant amounts of drugs may be conju- gated to the NCC surface. Furthermore, the hydroxyl groups on the surface of NCC can be modified with different func- tional groups, allowing the loading and release of drugs to be controlled (Akhlaghi et al. 2013). According to Basmaji et al. (2014), the use of BNC as a part of the extracellular matrix is a novel biotechnology and unique medicine indicated for chronic wound treat- ment and management, drug delivery, tissue engineering, and skin cancer. Additionally, this material offers a tangi- ble, effective solution to a serious medical and social problem, promoting rapid healing in lesions caused by diabetes, burns, ulcers of the lower limbs, or any other circumstances involving loss of epidermal or dermal tis- sue. In this context, novel antimicrobial peptides (AMPs) and bacterial cellulose/polyhexanide biguanide (PHMB), which are produced by symbioses culture between PHMB and green tea culture medium, result in a pure 3D struc- ture consisting of an ultrafine network of novel matrix comprising biocellulose/PHMB nanofibers (2–8 nm) that is highly hydrated (99 % in weight), has a high molecular weight, and exhibits good biocompatibility. Nimeskern et al. (2013) evaluated the potential applications of BNC as a graft material for replacement of ear cartilage. More- over, Bäckdahl et al. (2011) evaluated the applications of BNC as vascular grafts. Future trends In 10 years, many attempts have been made to isolate strains that exhibit efficient production of cellulose, and many sources have been shown to enhance BNC production How- ever, most studies have been performed using G. xylinus, and further analyses are needed to determine whether other bacte- rial strains may exhibit higher productivity. Additionally, stud- ies on the cost-effectiveness of culture medium have provided improvements to BNC yield and productivity. Because BNC is a material of great industrial interest, with applications in a variety of fields, further efforts are necessary to make this biotechnological material a competitive product and econom- ically viable. In brief, although several studies have investi- gated the applicability of BNC, many more studies are needed to explore the feasibility of biotechnological production, par- ticularly the cost effectiveness of culture medium. Thereby, permitting more applications of BNC especially on nanotech- nological area (i.e., nanoparticles for drug delivery, cosmetics, and food) and environmental (i.e., reduction of organic sol- vents or metals). 2070 Appl Microbiol Biotechnol (2016) 100:2063–2072 Acknowledgments The authors received grants from the Coordination for Higher Level Graduate Improvements (CAPES/Brazil), National Council for Scientific and Technological Development (CNPq/Brazil), and State of São Paulo Research Foundation (FAPESP/Brazil, process numbers 2009/14897-7 and 2013/08617-7). Compliance with ethical standards Ethical statement/conflict of interest The authors, whose names ap- pear on the submission, declare have contributed sufficiently to the sci- entific work and therefore share collective responsibility and accountabil- ity for the results. This manuscript has not been published or presented elsewhere in part or in entirety, and is not under consideration by another journal. There are no conflicts of interest to declare and this research not involved human participants or animals. All the authors have approved the manuscript and agree with submis- sion to your esteemed journal. References Akhlaghi SP, Berry RC, Tam KC (2013) Surface modification of cellu- lose nanocrystal with chitosan oligosaccharide for drug delivery applications. Cellulose 20:1747–1764. doi:10.1007/s10570-013- 9954-y Almeida IF, Pereira T, Silva NHCS, Gomes FP, Silvestre AJD, Freire CSR, Sousa Lobo JM, Costa PC (2014) Bacterial cellulose mem- branes as drug delivery systems: an in vivo skin compatibility study. Eur J Pharm Biopharm 86:332–336. doi:10.1016/j.ejpb.2013.08. 008 Ashjaran A, Yazdanshenas ME, Rashidi A, Khajavi R, Rezaee A (2013) Overview of bio nanofabric from bacterial cellulose. J Text Inst 104: 121–131. doi:10.1080/00405000.2012.703796 Bäckdahl H, Risberg B, Gatenholm P (2011) Observations on bacterial cellulose tube formation for application as vascular graft. Mater Sci Eng C 31:14–21. doi:10.1016/j.msec.2010.07.010 Basmaji P, de Olyveira GM, dos Santos ML, Guastaldi AC (2014) Novel antimicrobial peptides bacterial cellulose obtained by symbioses culture between polyhexanide biguanide (PHMB) and green tea. J Biomater Tissue Eng 4:59–64. doi:10.1166/jbt.2014.1133 Basta AH, El-Saied H (2009) Performance of improved bacterial cellu- lose application in the production of functional paper. J Appl Microbiol 107:2098–2107. doi:10.1111/j.1365-2672.2009.04467.x Cacicedo ML, Cesca K, Bosio VE, Porto LM, Castro GR (2015) Self- assembly of carrageenin–CaCO3 hybrid microparticles on bacterial cellulose films for doxorubicin sustained delivery. J Appl Biomed 13:239–248. doi:10.1016/j.jab.2015.03.004 Cai Z, Kim J (2009) Bacterial cellulose/poly(ethylene glycol) composite: characterization and first evaluation of biocompatibility. Cellulose 17:83–91. doi:10.1007/s10570-009-9362-5 Cakar F, Ozer I, Aytekin AÖ, Sahin F (2014) Improvement production of bacterial cellulose by semi-continuous process in molasses medium. Carbohydr Polym 106:7–13. doi:10.1016/j.carbpol.2014.01.103 Chawla PR, Bajaj IB, Survase SA, Singhal RS (2009) Microb Cellul : Fermentative Prod Appl 47:107–124 Conley K, Godbout L, Whitehead MA, Tony, Van De Ven TGM (2016) Origin of the twist of cellulosic materials. Carbohydr Polym 135: 285–299. doi:10.1016/j.carbpol.2015.08.029 Czaja W, Romanovicz D, Brown malcolm R (2004) Structural investiga- tions of microbial cellulose produced in stationary and agitated cul- ture. Cellulose 11:403–411. doi:10.1023/B:CELL.0000046412. 11983.61 Czaja WK, Young DJ, Kawecki M, Brown RM (2007) The future pros- pects of microbial cellulose in biomedical applications 8:1–12 de Azeredo HMC (2013) Antimicrobial nanostructures in food packag- ing. Trends Food Sci Technol 30:56–69. doi:10.1016/j.tifs.2012.11. 006 Donini I, De Salvi D, Fukumoto F, Lustri W, Barud H, Marchetto R, Messaddeq Y, Ribeiro S (2010) Biossíntese e recentes avanços na produção de celulose bacteriana. Eclética Química 35:165–178 Erbas Kiziltas E, Kiziltas A, Blumentritt M, Gardner DJ (2015a) Biosynthesis of bacterial cellulose in the presence of different nano- particles to create novel hybrid materials. Carbohydr Polym 129: 148–155. doi:10.1016/j.carbpol.2015.04.039 Erbas Kiziltas E, Kiziltas A, Gardner DJ (2015b) Synthesis of bacterial cellulose using hot water extracted wood sugars. Carbohydr Polym 124:131–138. doi:10.1016/j.carbpol.2015.01.036 Fu L, Zhang J, Yang G (2013) Present status and applications of bacterial cellulose-based materials for skin tissue repair. Carbohydr Polym 92:1432–1442. doi:10.1016/j.carbpol.2012.10.071 Gomes FP, Silva NHCS, Trovatti E, Serafim LS, Duarte MF, Silvestre AJD, Neto CP, Freire CSR (2013) Production of bacterial cellulose by Gluconacetobacter sacchari using dry olive mill residue. Biomass Bioenergy 55:205–211. doi:10.1016/j.biombioe.2013.02. 004 Hu Y, Catchmark JM (2010) Influence of 1-methylcyclopropene (1- MCP) on the production of bacterial cellulose biosynthesized by Acetobacter xylinum under the agitated culture. Lett Appl Microbiol 51:109–113. doi:10.1111/j.1472-765X.2010.02866 Hu W, Chen S, Yang J, Li Z, Wang H (2014) Functionalized bacterial cellulose derivatives and nanocomposites. Carbohydr Polym 101: 1043–1060. doi:10.1016/j.carbpol.2013.09.102 Huang C, Guo H-J, Xiong L, Wang B, Shi S-L, Chen X-F, Lin X-Q, Wang C, Luo J, Chen X-D (2016) Using wastewater after lipid fermentation as substrate for bacterial cellulose production by Gluconacetobacter xylinus. Carbohydr Polym 136:198–202. doi: 10.1016/j.carbpol.2015.09.043 Jeon S, Yoo Y-M, Park J-W, Kim H-J, Hyun J (2014) Electrical conduc- tivity and optical transparency of bacterial cellulose based composite by static and agitated methods. Curr Appl Phys 14:1621–1624. doi: 10.1016/j.cap.2014.07.010 Jozala AF, Aparecida R, Pértile N, Alves C (2015) Bacterial cellulose production by Gluconacetobacter xylinus by employing alternative culture media. ApplMicrobiol Biotechnol 99(3):1181–1190. doi:10. 1007/s00253-014-6232-3 Jung H-I, Lee O-M, Jeong J-H, Jeon Y-D, Park K-H, Kim H-S, An W-G, Son H-J (2010) Production and characterization of cellulose by Acetobacter sp. V6 using a cost-effective molasses-corn steep liquor medium. Appl Biochem Biotechnol 162:486–497. doi:10.1007/ s12010-009-8759-9 Keshk S, Sameshima K (2006) Influence of lignosulfonate on crystal structure and productivity of bacterial cellulose in a static culture. Enzym Microb Technol 40:4–8. doi:10.1016/j.enzmictec.2006.07. 037 Keshk SM (2014) Bacterial cellulose production and its industrial appli- cations. J Bioprocess Biotech 4:150. doi:10.4172/2155-9821. 1000150 Kim SS, Lee SY, Park KJ, Park SM, An HJ, Hyun JM, Choi YH (2015) Gluconacetobacter sp. gel_ SEA623-2, bacterial cellulose produc- ing bacterium isolated from citrus fruit juice. Saudi J Biol Sci. doi: 10.1016/j.sjbs.2015.09.031 Klemm D, Kramer F, Moritz S, Lindström T, Ankerfors M, Gray D, Dorris A (2011) Nanocelluloses: a new family of nature-based ma- terials. Angew Chem Int Ed Engl 50:5438–5466. doi:10.1002/anie. 201001273 Kralisch D, Hessler N, Klemm D, Erdmann R, Schmidt W (2010) White biotechnology for cellulose manufacturing - the HoLiR concept. Biotechnol Bioeng 105:740-747. doi:10.1002/bit.22579 Appl Microbiol Biotechnol (2016) 100:2063–2072 2071 http://dx.doi.org/10.1007/s10570-013-9954-y http://dx.doi.org/10.1007/s10570-013-9954-y http://dx.doi.org/10.1016/j.ejpb.2013.08.008 http://dx.doi.org/10.1016/j.ejpb.2013.08.008 http://dx.doi.org/10.1080/00405000.2012.703796 http://dx.doi.org/10.1016/j.msec.2010.07.010 http://dx.doi.org/10.1166/jbt.2014.1133 http://dx.doi.org/10.1111/j.1365-2672.2009.04467.x http://dx.doi.org/10.1016/j.jab.2015.03.004 http://dx.doi.org/10.1007/s10570-009-9362-5 http://dx.doi.org/10.1016/j.carbpol.2014.01.103 http://dx.doi.org/10.1016/j.carbpol.2015.08.029 http://dx.doi.org/10.1023/B:CELL.0000046412.11983.61 http://dx.doi.org/10.1023/B:CELL.0000046412.11983.61 http://dx.doi.org/10.1016/j.tifs.2012.11.006 http://dx.doi.org/10.1016/j.tifs.2012.11.006 http://dx.doi.org/10.1016/j.carbpol.2015.04.039 http://dx.doi.org/10.1016/j.carbpol.2015.01.036 http://dx.doi.org/10.1016/j.carbpol.2012.10.071 http://dx.doi.org/10.1016/j.biombioe.2013.02.004 http://dx.doi.org/10.1016/j.biombioe.2013.02.004 http://dx.doi.org/10.1111/j.1472-765X.2010.02866 http://dx.doi.org/10.1016/j.carbpol.2013.09.102 http://dx.doi.org/10.1016/j.carbpol.2015.09.043 http://dx.doi.org/10.1016/j.cap.2014.07.010 http://dx.doi.org/10.1007/s00253-014-6232-3 http://dx.doi.org/10.1007/s00253-014-6232-3 http://dx.doi.org/10.1007/s12010-009-8759-9 http://dx.doi.org/10.1007/s12010-009-8759-9 http://dx.doi.org/10.1016/j.enzmictec.2006.07.037 http://dx.doi.org/10.1016/j.enzmictec.2006.07.037 http://dx.doi.org/10.4172/2155-9821.1000150 http://dx.doi.org/10.4172/2155-9821.1000150 http://dx.doi.org/10.1016/j.sjbs.2015.09.031 http://dx.doi.org/10.1002/anie.201001273 http://dx.doi.org/10.1002/anie.201001273 http://dx.doi.org/10.1002/bit.22579 Krystynowicz A, Czaja W, Wiktorowska-Jezierska A, Gonçalves- Miśkiewicz M, Turkiewicz M, Bielecki S (2002) Factors affecting the yield and properties of bacterial cellulose. J Ind Microbiol Biotechnol 29:189–195. doi:10.1038/sj.jim.7000303 Kuo C-H, Chen J-H, Liou B-K, Lee C-K (2015) Utilization of acetate buffer to improve bacter ia l ce l lu lose product ion by Gluconacetobacter xylinus. Food Hydrocoll 53:98–103. doi:10. 1016/j.foodhyd.2014.12.034 Kurosumi A, Sasaki C, Yamashita Y, Nakamura Y (2009) Utilization of various fruit juices as carbon source for production of bacterial cel- lulose by Acetobacter xylinumNBRC 13693. Carbohydr Polym 76: 333–335. doi:10.1016/j.carbpol.2008.11.009 Lee K-Y, Buldum G, Mantalaris A, Bismarck A (2014) More than meets the eye in bacterial cellulose: biosynthesis, bioprocessing, and ap- plications in advanced fiber composites. Macromol Biosci 14:10– 32. doi:10.1002/mabi.201300298 Li Z, Wang L, Hua J, Jia S, Zhang J, Liu H (2015) Production of nano bacterial cellulose from waste water of candied jujube-processing industry using Acetobacter xylinum. Carbohydr Polym 120:115– 119. doi:10.1016/j.carbpol.2014.11.061 Lin N, Dufresne A (2014) Nanocellulose in biomedicine: current status and future prospect. Eur Polym J 59:302–325. doi:10.1016/j. eurpolymj.2014.07.025 Lin D, Lopez-Sanchez P, Li R, Li Z (2014) Production of bacterial cellu- lose by Gluconacetobacter hansenii CGMCC 3917 using only waste beer yeast as nutrient source. Bioresour Technol 151:113– 119. doi:10.1016/j.biortech.2013.10.052 Lu Z, Zhang Y, Chi Y, Xu N, YaoW, Sun B (2011) Effects of alcohols on bacterial cellulose production by Acetobacter xylinum 186. World J Microbiol Biotechnol 27:2281–2285. doi:10.1007/s11274-011- 0692-8 Lynd LR, Weimer PJ, van Zyl WH, Pretorius IS (2002) Microbial cellu- lose utilization: fundamentals and biotechnology. Microbiol Mol Biol Rev 66:506–577 Mautner A, Lee K-Y, Tammelin T, Mathew AP, Nedoma AJ, Li K, Bismarck A (2015) Cellulose nanopapers as tight aqueous ultra- filtration membranes. React Funct Polym 86:209–214. doi:10. 1016/j.reactfunctpolym.2014.09.014 Martínez-Sanz M, Lopez-Rubio A, Villano M, Oliveira CSS, Majone M, Reis M, Lagarón JM (2016) Product ion of bacter ia l nanobiocomposites of polyhydroxyalkanoates derived from waste and bacterial nanocellulose by the electrospinning enabling melt compounding method. J Appl Polym Sci 133. doi:10.1002/app. 42486 Mohammadkazemi F, Azin M, Ashori A (2015) Production of bacterial cellulose using different carbon sources and culture media. Carbohydr Polym 117:518–523. doi:10.1016/j.carbpol.2014.10.008 Molina de Olyveira G, Maria Manzine Costa L, Basmaji P (2013) Physically modified bacterial cellulose as alternative routes for transdermal drug delivery. J Biomater Tissue Eng 3:227–232. doi: 10.1166/jbt.2013.1079 Mikkelsen D, Flanagan BM, Dykes GA, Gidley MJ (2009) Influence of different carbon sources on bacterial cellulose production by Gluconacetobacter xylinus strain ATCC 53524. J Appl Microbiol 107:576–583. doi:10.1111/j.1365-2672.2009.04226.x Müller A, Ni Z, Hessler N, Wesarg F, Müller FA, Kralisch D, Fischer D (2013) The biopolymer bacterial nanocellulose as drug delivery sys- tem: investigation of drug loading and release using the model pro- tein albumin. J Pharm Sci 102:579–592. doi:10.1002/jps.23385 Nimeskern L, Martínez Ávila H, Sundberg J, Gatenholm P, Müller R, Stok KS (2013) Mechanical evaluation of bacterial nanocellulose as an implant material for ear cartilage replacement. J Mech Behav Biomed Mater 22:12–21. doi:10.1016/j.jmbbm.2013.03.005 Numata Y, Mazzarino L, Borsali R (2015a) A slow-release system of bacterial cellulose gel and nanoparticles for hydrophobic active ingredients. Int J Pharm 486:217–225. doi:10.1016/j.ijpharm.2015. 03.068 Numata Y, Sakata T, Furukawa H, Tajima K (2015b) Bacterial cellulose gels with high mechanical strength. Mater Sci Eng C Mater Biol Appl 47:57–62. doi:10.1016/j.msec.2014.11.026 Oliveira Barud HG, Barud Hda S, Cavicchioli M, do Amaral TS, de Oliveira Junior OB, Santos DM, Petersen AL, de OA, Celes F, Borges VM, de Oliveira CI, de Oliveira PF, Furtado RA, Tavares DC, SJL R (2015) Preparation and characterization of a bacterial cellulose/silk fibroin sponge scaffold for tissue regeneration. Carbohydr Polym 128:41–51. doi:10.1016/j.carbpol.2015.04.007 Padmanaban S, Balaji N, Muthukumaran C, Tamilarasan K (2015) Statistical optimization of process parameters for exopolysaccharide production by Aureobasidium pullulans using sweet potato based medium. Biotech 5:1067–1073. doi:10.1007/s13205-015-0308-3 Rajwade JM, Paknikar KM, Kumbhar JV (2015) Applications of bacte- rial cellulose and its composites in biomedicine. Appl Microbiol Biotechnol 99:2491–2511. doi:10.1007/s00253-015-6426-3 Rehim SA, Singhal M, Chung KC (2014) Dermal skin substitutes for upper limb reconstruction. Hand Clin 30:239–252. doi:10.1016/j. hcl.2014.02.001 Ruka DR, Simon GP, Dean KM (2012) Altering the growth conditions of Gluconacetobacter xylinus to maximize the yield of bacterial cellu- lose. Carbohydr Polym 89:613–622. doi:10.1016/j.carbpol.2012.03. 059 Santos-Ebinuma VC, Roberto IC, Simas Teixeira MF, Pessoa A (2013) Improving of red colorants production by a new Penicillium purpurogenum strain in submerged culture and the effect of different parameters in their stability. Biotechnol Prog 29:778–785. doi:10. 1002/btpr.1720 SchrammM, Hestrin S (1954) Factors affecting production of cellulose at the air/liquid interface of a culture of Acetobacter xylinum. J Gen Microbiol 11:123–129. doi:10.1099/00221287-11-1-123 Shah N, Ul-Islam M, Khattak WA, Park JK (2013) Overview of bacterial cellulose composites: a multipurpose advanced material. Carbohydr Polym 98:1585–1598. doi:10.1016/j.carbpol.2013.08.018 Shi Z, Zhang Y, Phillips GO, Yang G (2014) Utilization of bacterial cellulose in food. Food Hydrocoll 35:539–545. doi:10.1016/j. foodhyd.2013.07.012 Tanskul S, Amornthatree K, Jaturonlak N (2013) A new cellulose- producing bacterium, Rhodococcus sp.MI 2: screening and optimi- zation of culture conditions. Carbohydr Polym 92:421–428. doi:10. 1016/j.carbpol.2012.09.017 Thompson DN, Hamilton MA (2001) Production of bacterial cellulose from alternate feedstocks. Appl Biochem Biotechnol 91-93:503– 514. doi:10.1385/ABAB:91-93:1-9:503 Trovatti E, Serafim LS, Freire CSR, Silvestre AJD, Neto CP (2011) Gluconacetobacter sacchari: an efficient bacterial cellulose cell-fac- tory. Carbohydr Polym 86:1417–1420. doi:10.1016/j.carbpol.2011. 06.046 Tyagi N, Suresh S (2015) Production of cellulose from sugarcane molas- ses using Gluconacetobacter intermedius SNT-1: optimization & characterization. J Clean Prod. doi:10.1016/j.jclepro.2015.07.054 Wu J-M, Liu R-H (2012) Thin stillage supplementation greatly enhances bacterial cellulose production by Gluconacetobacter xylinus. Carbohydr Polym 90:116–121. doi:10.1016/j.carbpol.2012.05.003 Wu S-C, Li M-H (2015) Production of bacterial cellulose membranes in a modified airlift bioreactor by Gluconacetobacter xylinus. J Biosc Bioeng 120(4):444–449. doi:10.1016/j.jbiosc.2015.02.018 Zhang S, Winestrand S, Guo X, Chen L, Hong F, Jönsson LJ (2014) Effects of aromatic compounds on the production of bacterial nanocellulose by Gluconacetobacter xylinus. Microb Cell Factories 13:62. doi:10.1186/1475-2859-13-62 2072 Appl Microbiol Biotechnol (2016) 100:2063–2072 http://dx.doi.org/10.1038/sj.jim.7000303 http://dx.doi.org/10.1016/j.foodhyd.2014.12.034 http://dx.doi.org/10.1016/j.foodhyd.2014.12.034 http://dx.doi.org/10.1016/j.carbpol.2008.11.009 http://dx.doi.org/10.1002/mabi.201300298 http://dx.doi.org/10.1016/j.carbpol.2014.11.061 http://dx.doi.org/10.1016/j.eurpolymj.2014.07.025 http://dx.doi.org/10.1016/j.eurpolymj.2014.07.025 http://dx.doi.org/10.1016/j.biortech.2013.10.052 http://dx.doi.org/10.1007/s11274-011-0692-8 http://dx.doi.org/10.1007/s11274-011-0692-8 http://dx.doi.org/10.1016/j.reactfunctpolym.2014.09.014 http://dx.doi.org/10.1016/j.reactfunctpolym.2014.09.014 http://dx.doi.org/10.1002/app.42486 http://dx.doi.org/10.1002/app.42486 http://dx.doi.org/10.1016/j.carbpol.2014.10.008 http://dx.doi.org/10.1166/jbt.2013.1079 http://dx.doi.org/10.1111/j.1365-2672.2009.04226.x http://dx.doi.org/10.1002/jps.23385 http://dx.doi.org/10.1016/j.jmbbm.2013.03.005 http://dx.doi.org/10.1016/j.ijpharm.2015.03.068 http://dx.doi.org/10.1016/j.ijpharm.2015.03.068 http://dx.doi.org/10.1016/j.msec.2014.11.026 http://dx.doi.org/10.1016/j.carbpol.2015.04.007 http://dx.doi.org/10.1007/s13205-015-0308-3 http://dx.doi.org/10.1007/s00253-015-6426-3 http://dx.doi.org/10.1016/j.hcl.2014.02.001 http://dx.doi.org/10.1016/j.hcl.2014.02.001 http://dx.doi.org/10.1016/j.carbpol.2012.03.059 http://dx.doi.org/10.1016/j.carbpol.2012.03.059 http://dx.doi.org/10.1002/btpr.1720 http://dx.doi.org/10.1002/btpr.1720 http://dx.doi.org/10.1099/00221287-11-1-123 http://dx.doi.org/10.1016/j.carbpol.2013.08.018 http://dx.doi.org/10.1016/j.foodhyd.2013.07.012 http://dx.doi.org/10.1016/j.foodhyd.2013.07.012 http://dx.doi.org/10.1016/j.carbpol.2012.09.017 http://dx.doi.org/10.1016/j.carbpol.2012.09.017 http://dx.doi.org/10.1385/ABAB:91-93:1-9:503 http://dx.doi.org/10.1016/j.carbpol.2011.06.046 http://dx.doi.org/10.1016/j.carbpol.2011.06.046 http://dx.doi.org/10.1016/j.jclepro.2015.07.054 http://dx.doi.org/10.1016/j.carbpol.2012.05.003 http://dx.doi.org/10.1016/j.jbiosc.2015.02.018 http://dx.doi.org/10.1186/1475-2859-13-62 Bacterial nanocellulose production and application: a 10-year overview Abstract Introduction Cellulose Biotechnology-based production of BNC Applications of BNC Future trends References