Bacterial Cellulose: Production, Modification and Perspectives in Biomedical Applications

Abstract

Bacterial cellulose (BC) is ultrafine, nanofibrillar material with an exclusive combination of properties such as high crystallinity (84%-89%) and polymerization degree, high surface area (high aspect ratio of fibers with diameter 20-100 nm), high flexibility and tensile strength (Young modulus of 15-18 GPa), high water-holding capacity (over 100 times of its own weight), etc. Due to high purity, i.e., absence of lignin and hemicellulose, BC is considered as a non-cytotoxic, non-genotoxic and highly biocompatible material, attracting interest in diverse areas with hallmarks in medicine. The presented review summarizes the microbial aspects of BC production (bacterial strains, carbon sources and media) and versatile in situ and ex situ methods applied in BC modification, especially towards bionic design for applications in regenerative medicine, from wound healing and artificial skin, blood vessels, coverings in nerve surgery, dura mater prosthesis, arterial stent coating, cartilage and bone repair implants, etc. The paper concludes with challenges and perspectives in light of further translation in highly valuable medical products.

Keywords: bacterial cellulose; biomedical applications; carbon source; ex situ modification; in situ modification.

Figure 8

(a) BC dressings as produced and when applied on wounded torso, face and hand. Reproduced from [106], with permission from Biomacromolecules, 2007; (b) vascular graft and blood vessel tubes with different sizes and shape, produced by fermentation onto a branched silicone tube. Reproduced from [107,108,109], with permission from Frontiers, 2016, European Polymer Journal, 2014 and Biotechnology and Bioengeneering, 2007, respectively.

Figure 1

Scheme presenting the most important aspects which have to be considered for bacterial cellulose (BC)-production with biomedical application.

Figure 2

Influence of different organic acids and ethanol on cellulose yield. Reproduced from [21] with permission from Research & Reviews: Journal of Microbiology and Biotechnology, 2016.

Figure 3

Static production of cellulose by Komagataeibacter maltaceti 1529^T on complex microbiological medium.

Figure 4

Different length-scale presentation of BC: (A) photographs of wet (left) and dry (right) BC membrane, (B) confocal fluorescent microscopy (CFM) image obtained under argon laser excitation at 458 nm from bright field and fluorescence channel, utilizing the cellulose autofluorescence and (C) high magnification scanning electron microscopy (SEM) image presenting entrapped K. xylinus bacteria and cellulose backbone insert.

Figure 5

Synthesis of 6CF-BC by in situ microbial fermentation method, using glucose (Glc) modified with 6CF as a carbon source for K. sucrofermentans fermentation. (a) Glc and 6CF-Glc molecules; (b) microorganism fermentation; (c) the synthesis of 6CF-BC fibers through K. sucrofermentans, (d) microstructure of 6CF-BC; (e) the 6CF-BC pellicle obtained through microorganism fermentation. Reproduced from [65], with permission from Nature Communications, 2019.

Figure 6

Schematic presentation of the BC foam formation process by K. xylinus suspension foaming and stabilization by Cremodan and xanthan as a thickener. Reproduced from [75], with permission from npj Biofilms and Microbiomes, 2018.

Figure 7

Scanning electron microscopy images of (A) native and post-synthetically modified BC; (B) oxidation with NaIO₄; (C) further coupling with gelatin (GEL), carbodiimide crosslinking and freeze-thawing; (D) in situ mineralization by incubation in (10× concentrated) simulated body fluid medium. Adapted from [92], with permission from Nanomaterials, 2019.

Figure 9

(a) Fluorescent microscopy images of top, bottom and cross-section aspect of BC-gelatin composite membranes; (b) their degradation kinetic; (c) barrier effect towards MRC-5 cells. Adapted from [92], with permission from Nanomaterials, 2019.