细菌纤维素在生物医学材料中应用的研究进展

细菌纤维素是一种天然的生物高聚物,具有生物活性、生物可降解性、生物适应性,具有独特的物理、化学和机械性能,例如高的结晶度、高的持水性、超细纳米纤维网络、高抗张强度和弹性模量等,因而成为近来国际上新型生物医学材料的研究热点。本文概括了细菌纤维素的性质、研究历史以及在生物医学材料上的应用,重点阐述了细菌纤维素在组织工程支架、人工血管、人工皮肤和治疗皮肤损伤方面的应用以及当前研究现状。     

Latest Advances on Bacterial Cellulose‐Based Materials for Wound Healing,Delivery Systems,and Tissue Engineering

Bacterial cellulose (BC) is a nanocellulose form produced by some nonpathogenic bacteria. BC presents unique physical, chemical, and biological properties that make it a very versatile material and has found application in several fields, namely in food industry, cosmetics, and biomedicine. This review overviews the latest state‐of‐the‐art usage of BC on three important areas of the biomedical field, namely delivery systems, wound dressing and healing materials, and tissue engineering for regenerative medicine. BC will be reviewed as a promising biopolymer for the design and development of innovative materials for the mentioned applications. Overall, BC is shown to be an effective and versatile carrier for delivery systems, a safe and multicustomizable patch or graft for wound dressing and healing applications, and a material that can be further tuned to better adjust for each tissue engineering application, by using different methods.     

Increased yield and selected properties of bacterial cellulose exposed to different modes of a rotating magnetic field

Rotating magnetic field (RMF) is an interesting alternative to conventional bacterial cellulose (BC) production methods. The BC synthesis processes may be affected by RMF, which facilitates the transfer of oxygen and nutrients from the media to the microbial cells. RMF may also directly influence the various physical and chemical properties of BC. The main aim of the present study was to evaluate the impact of the RMF on the BC in regard to its yield and material properties. The correlation between the efficiency of polymer production and the different time of exposure to the RMF was also analyzed to determine the conditions of lower energy consumption during the cellulose formation process. It was found that the Gluconacetobacter xylinus cultures exposed to the RMF for a half of the time of the entire cellulose production process (72 h), considering the results obtained in controls, synthesized BC more effectively than bacteria continuously exposed to the RMF for 144 h. Furthermore, the application of the RMF, regardless of the exposure mode, did not negatively affect the polymer material properties. It was concluded that the use of the RMF may provide a novel technique for altering cellulose biogenesis and may be used in multiple biotechnological applications.     

Bacterial cellulose: a versatile biopolymer for wound dressing applications

Although several therapeutic approaches are available for wound and burn treatment and much progress has been made in this area, room for improvement still exists, driven by the urgent need of better strategies to accelerate wound healing and recovery, mostly for cases of severe burned patients. Bacterial cellulose (BC) is a biopolymer produced by bacteria with several advantages over vegetal cellulose, such as purity, high porosity, permeability to liquid and gases, elevated water uptake capacity and mechanical robustness. Besides its biocompatibility, BC can be modified in order to acquire antibacterial response and possible local drug delivery features. Due to its intrinsic versatility, BC is the perfect example of a biotechnological response to a clinical problem. In this review, we assess the BC main features and emphasis is given to a specific biomedical application: wound dressings. The production process and the physical–chemical properties that entitle this material to be used as wound dressing namely for burn healing are highlighted. An overview of the most common BC composites and their enhanced properties, in particular physical and biological, is provided, including the different production processes. A particular focus is given to the biochemistry and genetic manipulation of BC. A summary of the current marketed BC-based wound dressing products is presented, and finally, future perspectives for the usage of BC as wound dressing are foreseen.     

Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals

Cellulosic nanomaterials provide a novel and sustainable platform for the production of high performance materials enabled by nanotechnology. Bacterial cellulose (BC) is a highly crystalline material and contains pure cellulose without lignin and hemicellulose. BC offers an opportunity to provide control of the products’ properties in-situ, via specific BC production methods and culture conditions. The BC potential in advanced material applications are hindered by a limited knowledge of optimal BC production conditions, efficient process scale-up, separation methods, and purification methods. There is a growing body of work on the production of bacterial cellulose nanocrystals (BCNs) from BC fibers. However, there is limited information regarding the effect of BC fibers’ characteristics on the production of nanocrystals. This review describes developments in BC and BCNs production methods and factors affecting their yield and physical characteristics.     

Overview of bacterial cellulose composites: A multipurpose advanced material

Bacterial cellulose (BC) has received substantial interest owing to its unique structural features and impressive physico-mechanical properties. BC has a variety of applications in biomedical fields, including use as biomaterial for artificial skin, artificial blood vessels, vascular grafts, scaffolds for tissue engineering, and wound dressing. However, pristine BC lacks certain properties, which limits its applications in various fields; therefore, synthesis of BC composites has been conducted to address these limitations. A variety of BC composite synthetic strategies have been developed based on the nature and relevant applications of the combined materials. BC composites are primarily synthesized through in situ addition of reinforcement materials to BC synthetic media or the ex situ penetration of such materials into BC microfibrils. Polymer blending and solution mixing are less frequently used synthetic approaches. BC composites have been synthesized using numerous materials ranging from organic polymers to inorganic nanoparticles. In medical fields, these composites are used for tissue regeneration, healing of deep wounds, enzyme immobilization, and synthesis of medical devices that could replace cardiovascular and other connective tissues. Various electrical products, including biosensors, biocatalysts, E-papers, display devices, electrical instruments, and optoelectronic devices, are prepared from BC composites with conductive materials. In this review, we compiled various synthetic approaches for BC composite synthesis, classes of BC composites, and applications of BC composites. This study will increase interest in BC composites and the development of new ideas in this field.     

Statistical optimization of bacterial cellulose production by Leifsonia soli and its physico-chemical characterization

Bacterial cellulose has multiple applications in various industries such as food, biomedical, textile due to its uniqueness of being a better bio-compatible coating agent, binding material, etc. In this study, optimization of the culture medium for producing BC from Leifsonia soli was carried out by selecting different parameters. Five significant factors such as maltose, pH, incubation days, soy whey and calcium chloride were estimated through ANOVA based response surface methodology. Maximum cellulose production (5.97 g/L) was obtained where maltose 1 % (w/v) supplemented with 0.8 % (v/v) soy whey and calcium chloride 0.8 % (w/v) at pH 6.5 for 7 days of incubation. In addition, assurance of cellulose production from bacteria was done by using High-performance liquid chromatography analysis. Further, the structure and purity of obtained cellulose were examined by SEM and elemental analysis where it was observed that the sample holds the value of carbon 44.1 ± 0.20 % and hydrogen 6.2 ± 0.3 %, respectively. This study concludes that the addition of maltose and soy whey could be used as carbon, nitrogen sources and calcium chloride was used as an additive for the bacterial cellulose production compared to the Hestrin Schramm medium. In addition, the calculated water holding capacity of the sample was found to be 73 %.     

Bacterial cellulose as carrier for immobilization of laccase: Optimization and characterization

Bacterial cellulose (BC) has attracted attention as a new functional material due to its excellent mechanical strength, tridimensional nanostructure, high purity, and increased water absorption, compared to plant cellulose. In this work, commercial laccase was immobilized on BC and the influence of enzyme concentration, contact time, and pH was optimized toward the recovery activity of immobilized laccase. This optimization was carried out using a 3³ experimental design and response surface methodology. Enzyme concentration played a critical role in laccase immobilization. Under optimized conditions (0.15 μL L^?1 of enzyme concentration, 4.8 h of contact time, pH 5.4), the predicted and experimental response were equal to 47.88 and 49.30%, respectively. The thermal stability of the immobilized laccase was found to increase notably at 60 and 70°C presenting stabilization factor equal to 1.79 and 2.11, respectively. The immobilized laccase showed high operational stability, since it retained 86% of its initial activity after seven consecutive biocatalytic cycles of reaction with 2,2′‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid). Kinetic studies showed that the values of Michaelis–Menten constant and maximum reaction rate decreased upon immobilization (9.9‐ and 1.6‐fold, respectively). Globally, the use of immobilized laccase on BC offers an interesting tool for industrial biocatalytic applications.     

Polylactic acid: synthesis and biomedical applications

Social and economic development has driven considerable scientific and engineering efforts on the discovery, development and utilization of polymers. Polylactic acid (PLA) is one of the most promising biopolymers as it can be produced from nontoxic renewable feedstock. PLA has emerged as an important polymeric material for biomedical applications on account of its properties such as biocompatibility, biodegradability, mechanical strength and process ability. Lactic acid (LA) can be obtained by fermentation of sugars derived from renewable resources such as corn and sugarcane. PLA is thus an eco-friendly nontoxic polymer with features that permit use in the human body. Although PLA has a wide spectrum of applications, there are certain limitations such as slow degradation rate, hydrophobicity and low impact toughness associated with its use. Blending PLA with other polymers offers convenient options to improve associated properties or to generate novel PLA polymers/blends for target applications. A variety of PLA blends have been explored for various biomedical applications such as drug delivery, implants, sutures and tissue engineering. PLA and their copolymers are becoming widely used in tissue engineering for function restoration of impaired tissues due to their excellent biocompatibility and mechanical properties. The relationship between PLA material properties, manufacturing processes and development of products with desirable characteristics is described in this article. LA production, PLA synthesis and their applications in the biomedical field are also discussed.     

Improvement of biofouling resistance on bacterial cellulose membranes

Bacterial cellulose possesses excellent biocompatibility and mechanical strength that show great potentials for biomaterial applications. In this study, the surface modifications of bacterial cellulose (BC) membranes were facilitated using either simple coating or chemical grafting methods. The surface coating method is to simply immobilize BC membranes with poly(ethylene glycol) (PEG) solutions of concentration from 1 to 10%, followed by post-treatment with argon (Ar) plasma. The chemical method involved grafting mPEG (monofunctional methyl ether PEG) on BCs. The outcomes of surface modifications were characterized by surface chemical compositions (electron spectroscopy for chemical analysis (ESCA), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetry analysis (TGA), and surface morphology (atomic force microscopy (AFM) and scanning electron microscopy (SEM)). The effects of resistance to biofouling were verified by quantifying the adsorption of proteins and mammalian cells. The results showed that the PEG coating on BCs improved the resistance to cell adhesion by more than 30%. On the other hand, the specific chemical grafting resulted in a particularly high resistance to biofouling that the density of adherent cells reduced by more than 70% when compared to that on pristine BC. We have demonstrated that the two proposed methods were effective for the preparation of bioinert BC membranes with great potentials for applications in biomaterials and tissue engineering.     

Production of nanocellulose in miniature-bioreactor: Optimization and characterization

Bacterial cellulose (BC) is a very fascinating microbial biopolymer which is mainly produced by Gluconacetobacter xylinum. Optimization of BC production by G. xylinum was performed based on scale-down studies in miniature-bioreactor and response surface methodology in which the optimum pH value (6.5) and shaking rate (50?rpm) were obtained. The static culture condition for BC production has newly been defined. Nanostructure of BC includes nanofibers up to (60?nm) and nanoporosity up to (265?nm) was observed by scanning electron microscopy. By Fourier transform infrared spectroscopy study, the most expected BC interaction is nucleophilic interaction. MTT assay showed high biocompatibility. Appropriate mechanical strength (0.37?MPa) and Young’s modulus (3.36?MPa) evinced BC scaffold utilization for skin tissue. The results indicate that BC sheets can be utilized in biomedical application and nanotechnology approaches.     

Enhanced production of bacterial cellulose by using a biofilm reactor and its material property analysis

Bacterial cellulose has been used in the food industry for applications such as low-calorie desserts, salads, and fabricated foods. It has also been used in the paper manufacturing industry to enhance paper strength, the electronics industry in acoustic diaphragms for audio speakers, the pharmaceutical industry as filtration membranes, and in the medical field as wound dressing and artificial skin material. In this study, different types of plastic composite support (PCS) were implemented separately within a fermentation medium in order to enhance bacterial cellulose (BC) production by Acetobacter xylinum. The optimal composition of nutritious compounds in PCS was chosen based on the amount of BC produced. The selected PCS was implemented within a bioreactor to examine the effects on BC production in a batch fermentation. The produced BC was analyzed using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), and dynamic mechanical analysis (DMA). Among thirteen types of PCS, the type SFYR+ was selected as solid support for BC production by A. xylinum in a batch biofilm reactor due to its high nitrogen content, moderate nitrogen leaching rate, and sufficient biomass attached on PCS. The PCS biofilm reactor yielded BC production (7.05 g/L) that was 2.5-fold greater than the control (2.82 g/L). The XRD results indicated that the PCS-grown BC exhibited higher crystallinity (93%) and similar crystal size (5.2 nm) to the control. FESEM results showed the attachment of A. xylinum on PCS, producing an interweaving BC product. TGA results demonstrated that PCS-grown BC had about 95% water retention ability, which was lower than BC produced within suspended-cell reactor. PCS-grown BC also exhibited higher T _max compared to the control. Finally, DMA results showed that BC from the PCS biofilm reactor increased its mechanical property values, i.e., stress at break and Young's modulus when compared to the control BC. The results clearly demonstrated that implementation of PCS within agitated fermentation enhanced BC production and improved its mechanical properties and thermal stability.     

Invited review nonmulberry silk biopolymers

The silk produced by silkworms are biopolymers and can be classified into two types--mulberry and nonmulberry. Mulberry silk of silkworm Bombyx mori has been extensively explored and used for century old textiles and sutures. But for the last few decades it is being extensively exploited for biomedical applications. However, the transformation of nonmulberry silk from being a textile commodity to biomaterials is relatively new. Within a very short period of time, the combination of load bearing capability and tensile strength of nonmulberry silk has been equally envisioned for bone, cartilage, adipose, and other tissue regeneration. Adding to its advantage is its diverse morphology, including macro to nano architectures with controllable degradation and biocompatibility yields novel natural material systems in vitro. Its follow on applications involve sustained release of model compounds and anticancer drugs. Its 3D cancer models provide compatible microenvironment systems for better understanding of the cancer progression mechanism and screening of anticancer compounds. Diversely designed nonmulberry matrices thus provide an array of new cutting age technologies, which is unattainable with the current synthetic materials that lack biodegradability and biocompatibility. Scientific exploration of nonmulberry silk in tissue engineering, regenerative medicine, and biotechnological applications promises advancement of sericulture industries in India and China, largest nonmulberry silk producers of the world. This review discusses the prospective biomedical applications of nonmulberry silk proteins as natural biomaterials.     

Bacterial Cellulose as a Substrate for Microbial Cell Culture

Bacterial cellulose (BC) has a range of structural and physicochemical properties that make it a particularly useful material for the culture of bacteria. We studied the growth of 14 genera of bacteria on BC substrates produced by Acetobacter xylinum and compared the results to growth on the commercially available biopolymers agar, gellan, and xanthan. We demonstrate that BC produces rates of bacterial cell growth that typically exceed those on the commercial biopolymers and yields cultures with higher titers of cells at stationary phase. The morphology of the cells did not change during growth on BC. The rates of nutrient diffusion in BC being higher than those in other biopolymers is likely a primary factor that leads to higher growth rates. Collectively, our results suggest that the use of BC may open new avenues in microbiology by facilitating bacterial cell culture and isolation.     

Biocellulose membranes as supports for dermal release of lidocaine

Biocellulose (BC) is a highly pure form of cellulose, produced in the form of a swollen membrane, with several applications in the biomedical area. In this study, the behavior of BC membranes as systems for topical delivery of lidocaine was evaluated. The BC-lidocaine membranes were prepared and characterized in terms of structural and morphological properties. A uniform distribution of the drug inside the BC membranes was observed. In vitro diffusion studies with Franz cells were conducted using human epidermal membranes and showed that the permeation rate of the drug in BC membranes was slightly slower than that obtained with the conventional systems, which was attributed to the establishment of interactions between the lidocaine molecules and the BC membrane, as evidenced by FTIR and NMR analysis. These results indicate that this methodology can be successfully applied for the dermal administration of lidocaine regarding the release profile and ease of application.     

The future prospects of microbial cellulose in biomedical applications

Microbial cellulose has proven to be a remarkably versatile biomaterial and can be used in wide variety of applied scientific endeavors, such as paper products, electronics, acoustics, and biomedical devices. In fact, biomedical devices recently have gained a significant amount of attention because of an increased interest in tissue-engineered products for both wound care and the regeneration of damaged or diseased organs. Due to its unique nanostructure and properties, microbial cellulose is a natural candidate for numerous medical and tissue-engineered applications. For example, a microbial cellulose membrane has been successfully used as a wound-healing device for severely damaged skin and as a small-diameter blood vessel replacement. The nonwoven ribbons of microbial cellulose microfibrils closely resemble the structure of native extracellular matrices, suggesting that it could function as a scaffold for the production of many tissue-engineered constructs. In addition, microbial cellulose membranes, having a unique nanostructure, could have many other uses in wound healing and regenerative medicine, such as guided tissue regeneration (GTR), periodontal treatments, or as a replacement for dura mater (a membrane that surrounds brain tissue). In effect, microbial cellulose could function as a scaffold material for the regeneration of a wide variety of tissues, showing that it could eventually become an excellent platform technology for medicine. If microbial cellulose can be successfully mass produced, it will eventually become a vital biomaterial and will be used in the creation of a wide variety of medical devices and consumer products.     

Bacterial cellulose modified using recombinant proteins to improve neuronal and mesenchymal cell adhesion

A wide variety of biomaterials and bioactive molecules have been applied as scaffolds in neuronal tissue engineering. However, creating devices that enhance the regeneration of nervous system injuries is still a challenge, due the difficulty in providing an appropriate environment for cell growth and differentiation and active stimulation of nerve regeneration. In recent years, bacterial cellulose (BC) has emerged as a promising biomaterial for biomedical applications because of its properties such as high crystallinity, an ultrafine fiber network, high tensile strength, and biocompatibility. The small signaling peptides found in the proteins of extracellular matrix are described in the literature as promoters of adhesion and proliferation for several cell lineages on different surfaces. In this work, the peptide IKVAV was fused to a carbohydrate-binding module (CBM3) and used to modify BC surfaces, with the goal of promoting neuronal and mesenchymal stem cell (MSC) adhesion. The recombinant proteins IKVAV-CBM3 and (19)IKVAV-CBM3 were successfully expressed in E. coli, purified through affinity chromatography, and stably adsorbed to the BC membranes. The effect of these recombinant proteins, as well as RGD-CBM3, on cell adhesion was evaluated by MTS colorimetric assay. The results showed that the (19)IKVAV-CBM3 was able to significantly improve the adhesion of both neuronal and mesenchymal cells and had no effect on the other cell lineages tested. The MSC neurotrophin expression in cells grown on BC membranes modified with the recombinant proteins was also analyzed.     

Recombinant DNA production of spider silk proteins

Spider dragline silk is considered to be the toughest biopolymer on Earth due to an extraordinary combination of strength and elasticity. Moreover, silks are biocompatible and biodegradable protein-based materials. Recent advances in genetic engineering make it possible to produce recombinant silks in heterologous hosts, opening up opportunities for large-scale production of recombinant silks for various biomedical and material science applications. We review the current strategies to produce recombinant spider silks.     

Life cycle assessment of bacterial cellulose production

The International Journal of Life Cycle Assessment - Bacterial cellulose (BC), obtained by fermentation, is an innovative and promising material with a broad spectrum of potential applications....     

Applications of functionalized and nanoparticle-modified nanocrystalline cellulose

Nanocrystalline cellulose (NCC), a rod-shaped nanoscale material with exceptional strength and physicochemical properties, can be prepared from inexpensive renewable biomass. Besides its potential use as a reinforcing agent for industrial biocomposites, pristine NCC exhibits low toxicity and poses no serious environmental concerns, providing impetus for its use in bioapplications. Here, we review recent developments in the use of modified NCC for emerging bioapplications, specifically enzyme immobilization, antimicrobial and medical materials, green catalysis, biosensing and controlled drug delivery. We focus on the modification of NCC with chemical functionalities and inorganic nanoparticles, reviewing practical considerations such as reusability, toxicity and scale-up capability.