Bacterial Cellulose Composites Research Articles

Effects of the modification of bacterial cellulose as a template for the in situ enzyme-catalyzed polymerization of catechol

In this study, we investigated the effects of the modification of bacterial cellulose used as a template on the in situ polymerization of catechol by laccase. The bacterial cellulose was modified by sulfonation and the entrapment of carboxymethyl cellulose. The catechol polymerization was optimized at a pH of 5.5, catechol concentration of 50 mM, and synthesis time of 24 h. After the in situ polymerization, conductive and colored bacterial cellulose composites were obtained. The bacterial cellulose composites containing oligomers/polymers were analyzed using Fourier-transform infrared spectroscopy, scanning electron microscopy, and color strength measurements, and the conductivity of the bacterial cellulose composites was evaluated using a four-probe method. The results revealed that the modification of bacterial cellulose as a template for catechol oxidation resulted in the production of fibers with enhanced coloration and conductive properties owing to the presence of the enzymatically-obtained polymers. The results suggest the promising potential of both sulfonated bacterial cellulose and carboxymethyl cellulose-bacterial cellulose as templates for the formation of other functional polymers and composite materials.

Bacterial Cellulose-Based Materials as Dressings for Wound Healing.

Bacterial cellulose (BC) is produced by several microorganisms as extracellular structures and can be modified by various physicochemical and biological strategies to produce different cellulosic formats. The main advantages of BC for biomedical applications can be summarized thus: easy moldability, purification, and scalability; high biocompatibility; and straightforward tailoring. The presence of a high amount of free hydroxyl residues, linked with water and nanoporous morphology, makes BC polymer an ideal candidate for wound healing. In this frame, acute and chronic wounds, associated with prevalent pathologies, were addressed to find adequate therapeutic strategies. Hence, the main characteristics of different BC structures-such as membranes and films, fibrous and spheroidal, nanocrystals and nanofibers, and different BC blends, as well as recent advances in BC composites with alginate, collagen, chitosan, silk sericin, and some miscellaneous blends-are reported in detail. Moreover, the development of novel antimicrobial BC and drug delivery systems are discussed.

Bacterial Cellulose-Carboxymethylcellulose Composite Loaded with Turmeric Extract for Antimicrobial Wound Dressing Applications.

Bacterial cellulose (BC) is a biopolymer whose properties have been intensively studied, especially for biomedical applications. Since BC has no antimicrobial activity, it is necessary to use bioactive substances for developing wound healing applications. Another drawback of BC is the loss if its water retention capacity after dehydration. In order to overcome these problems, carboxymethyl cellulose (CMC) and turmeric extract (TE) were selected for the preparation of BC composites. Citric acid (CA) was used as the crosslinking agent. These composites were tested as potential antimicrobial wound dressing materials. TE-loaded BC-CMC composites were characterized in terms of their morphology, crystallinity, and thermal behavior. Swelling tests and curcumin-release kinetic analysis were also performed. All the composites tested had high swelling degrees, which is an advantage for the exudate adsorption from chronic wounds. The antibacterial potential of such composites was tested against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Candida albicans (C. albicans). The in vitro cytotoxicity toward L929 fibroblast cells was studied as well. The obtained results allow us to recommend these composites as good candidates for wound dressing applications.

A Mini-review for the Application of Bacterial Cellulose-based Composites

Countries are duly focusing more on biomass resources because of the increasing oil crisis. Owing to their excellent properties, such as natural characteristics, good mechanical performance, and outstanding chemical properties, cellulose-based materials are highly valued as promising bio-derived nanomaterials, especially bacterial cellulose (BC). The main advantage lies in eliminating the problem of removing lignin and hemicellulose from woody cellulose. Moreover, the use of BC reduces the consumption of wood, the excessive use of which aggravates global warming. Herein, we summarize the applications of BC composites in filter, medical, and conductive materials, and other fields. This review contributes to further expand the applications of this renewable polymer.

Employed Bacterial Species and Bacterial Cellulose (BC) Applications: The State of Play

Bacterial cellulose (BC) is an uprising bio-polymer produced by various bacterial strains, which is infamous for its prominent biological properties and applications. Receiving ample attention due to those unique properties, various genus and bacterial strains have been used for BC biosynthesis and the studies of its production have been recorded throughout the years. Although a lot of research and implementation has been done on BC, studies in the search for low-cost, effective medium contributing to higher BC yields were still in continuation to this day. This review article overviews the employed bacterial strains and their recent advance, modified, and low-cost medium in the development of BC composites. Special emphasis is placed on the new-novel strains for BC production and BC applications. Compilations of literature were compiled to outline the sources and also findings by previous and recent researchers. It was found that numerous studies have attempted to enhance BC production, which includes the utilization of various bacterial strains to fulfill industrial needs. Hence, this review comprises bacterial genera and species, which are mainly used in the production of BC such as Komagataeibacter, Gluconobacter, Gluconacetobacter, Enterobacter, and Pseudomonas.The recent studies enforced on BC focusing on higher production and the application of BC on an industrial scale will also be reviewed.

Development of FexOy particle onto bacterial cellulose network by forced hydrolysis and its electrical conductivity

FexOy particle and bacterial cellulose composite sheet was successfully prepared by forced hydrolysis. The presence of Fe3+ ions in bacterial cellulose suspension significantly provided the positive charge due to electrostatic force as reported by Zeta potential. With the pH of 12 of bacterial cellulose suspension, particle was nucleated between bacterial cellulose networks. Fourier transform infrared exhibited Fe-O stretching. X-ray diffraction reported that the mixture of Fe2O3 and Fe3O4 was existed onto bacterial cellulose composite. Scanning electron microscope reported that FexOy particle was randomly distributed in bacterial cellulose network. Intensity of Fe was qualitatively observed by energy dispersive analysis. With the existence of FexOy particle, the composite illustrated the inferiority of thermal stability of 150℃. Furthermore, it was noted that the resistivity was reduced with respect to increment of FexOy particle, suggesting that electrical conductivity was then enhanced. It was remarkable to note that FexOy particle and bacterial cellulose composite sheet prepared from forced hydrolysis showed the excellent properties as a candidate for flexible electrode.

Bacterial Cellulose Hybrid Composites with Calcium Phosphate for Bone Tissue Regeneration.

Bacterial cellulose (BC) is a unique microbial biopolymer with a huge number of significant applications in the biomedical field, including bone tissue engineering. The present study proposes to obtain and characterize BC hybrid composites with calcium phosphate as biocompatible and bioactive membranes for bone tissue engineering. BC precursor membranes were obtained in static culture fermentation, and after purification, were oxidized to obtain 2,3-dialdehyde bacterial cellulose (DABC). Calcium phosphate-BC oxidized membranes were produced by successive immersion in precursor solutions under ultrasonic irradiation. The samples were characterized for their physicochemical properties using scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy grazing incidence X-ray diffraction (GI-XRD), solid-state 13C nuclear magnetic resonance (CP/MAS 13C NMR), and complex thermal analysis. In vitro cell studies were also performed to evaluate the influence of modified morphological characteristics on cell adhesion and proliferation. The results showed an increase in porosity and biodegradability for DABC hybrid composites compared with BC. In vitro cell studies have revealed that both hybrid composites favor cell adhesion to the surface. The new BC and DABC hybrid composites with calcium phosphate could be considered promising materials for bone tissue regeneration.

Low cost production of bacterial cellulose through statistical optimization and developing its composites for multipurpose applications

The current investigation reports the enhanced bacterial cellulose (BC) productivity from previously isolated bacteria, Enterobacter hormaechei subsp. steigerwaltii strain ZKE7 using different raw sources. Optimization by Plackett–Burman and central composite designs revealed improved BC production of 31.7 g/L BC (In-situ) with 7.54-fold enhancement. Different BC composites were synthesized using optimized In-situ BC that showed excellent water retention capability, moisture content, water release rate, porosity, thickness and protein adsorption. In vitro drug (methylene blue dye and ceftriaxone) release profile of the composites (BC-Cu and BC-CMC) suggested a sustained drug delivery and indicated a non-Fickian diffusion behavior based on Peppas model. The quick catalytic activity of BC-Cu in fast reduction of 4-nitrophenol was demonstrated spectrophotometrically with decline in the characteristic absorbance peak of 4-nitrophenol. In-situ BC and composites exhibited antimicrobial properties with differential activity against different pathogens. Significant antibacterial and inhibitory effect was evidenced against Bacillus cereus. Only In-situ BC showed a pronounced antifungal activity against Candida albicans. In-situ BC and composites were characterized by various analytical techniques including FTIR, SEM-EDS, TGA and DSC. The current study reveals enhanced BC yield with the reduction of 4-nitrophenol by BC-Cu composite and antimicrobial property suggests its employability in drug delivery systems and environmental applications.

Bacterial Cellulose Composites with Polysaccharides Filled with Nanosized Cerium Oxide: Characterization and Cytocompatibility Assessment.

A new biocompatible nanocomposite film material for cell engineering and other biomedical applications has been prepared. It is based on the composition of natural polysaccharides filled with cerium oxide nanoparticles (CeONPs). The preparative procedure consists of successive impregnations of pressed bacterial cellulose (BC) with a sodium alginate (ALG) solution containing nanoparticles of citrate-stabilized cerium oxide and a chitosan (CS) solution. The presence of CeONPs in the polysaccharide composite matrix and the interaction of the nanoparticles with the polymer, confirmed by IR spectroscopy, change the network architecture of the composite. This leads to noticeable changes in a number of properties of the material in comparison with those of the matrix's polysaccharide composition, viz., an increase in mechanical stiffness, a decrease in the degree of planar orientation of BC macrochains, an increase in hydrophilicity, and the shift of the processes of thermo-oxidative destruction of the material to a low-temperature region. The latter effect is considered to be caused by the redox activity of cerium oxide (reversible transitions between the states Ce4+ and Ce3+) in thermally stimulated processes in the nanocomposite films. In the equilibrium swollen state, the material retains a mechanical strength at the level of ~2 MPa. The results of in vitro tests (cultivation of multipotent mesenchymal stem cells) have demonstrated the good biocompatibility of the BC-ALG(CeONP)-CS film as cell proliferation scaffolds.

Insights into the contributions of hemicelluloses to assembly and mechanical properties of cellulose networks

In order to explore the contributions of hemicelluloses to the assembly and mechanical properties of cellulose networks, the bacterial cellulose (BC) composites containing xylan and glucomannan were prepared to mimic the polysaccharides network of plant cell walls. Both polysaccharides could induce the change of diameters of cellulose ribbons and influence the crystallization of cellulose. Besides, small-angle X-ray scattering (SAXS) demonstrated that xylan inhibited the assembly of microfibrils into cellulose ribbons, while glucomannan promoted the packing of microfibrils. The changes of cellulose crystalline structure and assembly pattern of cellulose contributed to the lower tensile strength and higher strain at break of the BC composites as compared with the BC. The results provide a profound insight into the structure-property relationships of cellulose networks affected by hemicelluloses, which could be conducive to the development of cellulose biomaterials.

Development of plant extract impregnated bacterial cellulose as a green antimicrobial composite for potential biomedical applications

The current study was designed to develop cost effective antibacterial bacterial cellulose (BC) composites without following the traditional method of metal nanoparticles or drug incorporation. Briefly, the waste of tomato was employed as the main carbon source instead of commonly used commercial glucose for BC synthesis by Gluconacetobacter hansenii . Further the bioactive extract of Dracaena serrulata (D. serrulata ) plant was impregnated into BC and the resulting BC- D. serrulata (BC-D) composites were investigated for their physicochemical and biological features. Field emission scanning electron microscopy (FE-SEM) micrographs illustrated the successful impregnation of plant extracts in between the BC fibers. Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction (XRD) analysis further confirmed the BC-D fabrication. Synthesized BC-D composites were able to withhold 115 % water of its dry weight. The antibacterial activities of BC-D composite were investigated against Escherichia coli and Staphylococcus aureus pathogens. A moderate level of activity was displayed at the extract level in MIC assays. BC-D composite displayed an inhibition zone of 0.7 mm and 0.5 mm against S. aureus and against E. coli, respectively . Besides moderate level of activity at extract level, BC-D composites exhibited impressive antibacterial activity where BC-D reduced the growth of S. aureus and E. coli from 70 % to 75 % in their live cell density while observed through optical density method. Moreover, this is the first study of exploring the antibacterial characteristics of D. serrulata plant extract and their composite with BC, which could be of vital significance for researchers to develop green biomedical materials . Furthermore, utilization of such wastes for bioproduct development can highly reduce the environmental risks associated with waste management and disposal. • Bacterial cellulose was produced from tomatoes waste. • The Dracaena serrulata leaves extract and bacterial cellulose were mixed to form composite. • Improved physical properties of BC composite were observed as compared to pure BC. • Adequate antibacterial characteristic was achieved with the use of Dracaena serrulata extract with MIC of 12.5 mg/mL.

Bacterial cellulose adhesive patches designed for soft mucosal interfaces

The wet environment in the oral cavity is challenging for topical disease management approaches. The compromised material properties leading to weak adhesion and short retention (<8 h) in such environment result in frequent reapplication of the therapeutics. Composites of bacterial cellulose (BC) and carbene-based bioadhesives attempt to address these shortcomings. Previous designs comprised of aqueous formulations. The current design, for the first time, presents dry, shelf-stable cellulose patches for convenient ready-to-use application. The dry patches simultaneously remove tissue surface hydration while retaining carbene-based photocuring and offers on-demand adhesion. The dry patch prototypes are optimized by controlling BC/adhesive mole ratios and dehydration technique. The adhesion strength is higher than commercial denture adhesives on soft mucosal tissues. The structural integrity is maintained for a minimum of 7 days in aqueous environment. The patches act as selective nanoporous barrier against bacteria while allowing permeation of proteins. The results support the application of BC-based adhesive patches as a flexible platform for wound dressings, drug depots, or combination thereof.

Fabrication of efficient protein imprinted materials based on pearl necklace-like MOFs bacterial cellulose composites

The acquisition of efficient protein isolation substances is vital for proteomic research, whereas it's still challenging nowadays. Herein, an elaborately designed protein imprinted material based on a bacterial cellulose@ZIF-67 composite carrier (BC@ZIF-67) is proposed for the first time. In particular, due to the ultrafine fiber diameter and abundant hydroxyl functional groups of the bacterial cellulose, BC@ZIF-67 presented a compact arrangement structure similar to a pearl necklace, which greatly promoted template immobilization and mass transfer resistance in protein imprinting technology. Therefore, the protein-imprinted material (BC@ZIF-67@MIPs) fabricated by surface imprinting technology and template immobilization strategy could exhibit ultrahigh adsorption capacity (1017.0 mg g−1), excellent recognition (IF = 5.98) and rapid adsorption equilibrium time (50 min). In addition, based on the experiment outcomes, our team employed BC@ZIF-67@MIPs to enrich template protein in blended protein solutions and biosamples, identifying them as underlying candidates for isolating and purifying proteins.

Bacterial cellulose/soybean protein isolate composites with promoted inflammation inhibition, angiogenesis and hair follicle regeneration for wound healing

Soybean protein, as a safe and low-cost alternative to animal protein, attracts increasing attention in wound healing. In the present study, beta-conglycinin (7S) and glycinin (11S) with high solubility were obtained through separation of soybean protein. Afterward, 7S or 11S modified bacterial cellulose (BC) composites were produced by self-assembly method. Results confirmed the successful self-assembly of soybean protein isolates on the nanofibers of BC. The surface roughness and hydrophilicity of BC/7S and BC/11S decreased compared with native BC. Soybean protein could be steadily released from BC/7S and BC/11S and BC/11S released more soybean proteins than BC/7S. In vitro, BC/7S and BC/11S supported fibroblasts attachment and promoted fibroblasts proliferation and type I collagen expression. In vivo, BC/7S and BC/11S facilitated wound healing and collagen deposition, enhanced angiogenesis and hair follicle regeneration, as well as reduced scar formation and inflammation in full-thickness skin wounds of rats. Moreover, wounds treated with BC/11S showed a faster wound healing rate and more collagen depositions than those of BC/7S, which may be attributed to the larger considerable amount of soybean protein released by BC/11S. These results indicate that BC/7S and BC/11S are potential candidates for wound dressings.

Silver impregnated bacterial cellulose-chitosan composite hydrogels for antibacterial and catalytic applications

The current study was aimed to develop bacterial cellulose (BC) composites synergistically with polymer (Chitosan (chi)) and a nanomaterial (green synthesized silver nanoparticles (AgNPs) using an Azadirachta indica leaves extract). BC-Chi-Ag composites were developed through ex-situ composite development strategy and evaluated for their structural, biological and catalytic activities. Field emission scanning electron microscopy (FE-SEM) displayed the impregnation of Chi and AgNPs in porous BC network. The composite formulation was further confirmed by the X-ray diffraction (XRD) analysis which showed the presence of additional crystallinic peaks together with pure BC ones. Bactericidal assays of BC-Chi-Ag composites against modern pathogen including Staphylococcus aureus and Escherichia coli depicted significant reduction in growth results compared to pure BC. Kapp value were found to be 0.37081 min−1 and 0.35108 min−1 for catalytic reduction of Rh B and 4-NP, respectively. High bactericidal and catalytic potentials of synthesized BC-Chi-Ag composites seriously justify their potential applications in medical and environmental fields.

An Artificial PVA-BC Composite That Mimics the Biomechanical Properties and Structure of a Natural Intervertebral Disc.

Disc herniation is one of the most ubiquitous healthcare problems in modern cities—severe patients eventually require surgical intervention. However, the existing operations—spinal fusion and artificial disc replacement—alter the biomechanics of the spine, leaving much room for improvement. The appropriateness of polyvinyl alcohol (PVA) for biomedical applications has been recognised due to its high water content, excellent biocompatibility, and versatile mechanical properties. In this study, a newly-designed PVA–bacterial cellulose (PVA-BC) composite was assembled to mimic both the biomechanics and annular structure of natural intervertebral discs (IVDs). PVA-BC composites of various concentrations were fabricated and tested under unconfined compression and compressive creep in order to acquire the values of the normalised compressive stiffness and whole normalised deformation. The normalised compressive stiffness increased considerably with an increasing PVA concentration, spanning from 1.82 (±0.18) to 3.50 (±0.14) MPa, and the whole normalised deformation decreased from 0.25 to 0.13. Formulations of 40% PVA provided the most accurate mimicry of natural human IVDs in normalised whole deformation, and demonstrated higher dimensional stability. The biocompatible results further confirmed that the materials had excellent biocompatibility. The novel bionic structure and formulations of the PVA-BC materials mimicked the biomechanics and structure of natural IVDs, and ensured dimensional stability under prolonged compression, reducing the risk of impingement on the surrounding tissue. The PVA-BC composite is a promising material for third-generation artificial IVDs with integrated construction.

Antimicrobial Food Packaging Based on Prodigiosin-Incorporated Double-Layered Bacterial Cellulose and Chitosan Composites.

Nowadays, food packaging systems have shifted from a passive to an active role in which the incorporation of antimicrobial compounds into biopolymers can promote a sustainable way to reduce food spoilage and its environmental impact. Accordingly, composite materials based on oxidized-bacterial cellulose (BC) and poly(vinyl alcohol)-chitosan (PVA-CH) nanofibers were produced by needleless electrospinning and functionalized with the bacterial pigment prodigiosin (PG). Two strategies were explored, in the first approach PG was incorporated in the electrospun PVA-CH layer, and TEMPO-oxidized BC was the substrate for nanofibers deposition (BC/PVA-CH_PG composite). In the second approach, TEMPO-oxidized BC was functionalized with PG, and afterward, the PVA-CH layer was electrospun (BC_PG/PVA-CH composite). The double-layer composites obtained were characterized and the nanofibrous layers displayed smooth fibers with average diameters of 139.63 ± 65.52 nm and 140.17 ± 57.04 nm, with and without pigment incorporation, respectively. FTIR-ATR analysis confirmed BC oxidation and revealed increased intensity at specific wavelengths, after pigment incorporation. Moreover, the moderate hydrophilic behavior, as well as the high porosity exhibited by each layer, remained mostly unaffected after PG incorporation. The composites’ mechanical performance and the water vapor transmission rate (WVTR) evaluation indicated the suitability of the materials for certain food packaging solutions, especially for fresh products. Additionally, the red color provided by the bacterial pigment PG on the external surface of a food packaging material is also a desirable effect, to attract the consumers’ attention, creating a multifunctional material. Furthermore, the antimicrobial activity was evaluated and, PVA-CH_PG, and BC_PG layers exhibited the highest antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Thus, the fabricated composites can be considered for application in active food packaging, owing to PG antimicrobial potential, to prevent foodborne pathogens (with PG incorporated into the inner layer of the food packaging material, BC/PVA-CH_PG composite), but also to prevent external contamination, by tackling the exterior of food packaging materials (with PG added to the outer layer, BC_PG/PVA-CH composite).

Bacterial Cellulose (BC) and BC Composites: Production and Properties.

The synthesis of bacterial cellulose (BC) by Komagataeibacter xylinus strain B-12068 was investigated on various C-substrates, under submerged conditions with stirring and in static surface cultures. We implemented the synthesis of BC on glycerol, glucose, beet molasses, sprat oil, and a mixture of glucose with sunflower oil. The most productive process was obtained during the production of inoculum in submerged culture and subsequent growth of large BC films (up to 0.2 m2 and more) in a static surface culture. The highest productivity of the BC synthesis process was obtained with the growth of bacteria on molasses and glycerol, 1.20 and 1.45 g/L per day, respectively. We obtained BC composites with silver nanoparticles (BC/AgNPs) and antibacterial drugs (chlorhexidine, baneocin, cefotaxime, and doripenem), and investigated the structure, physicochemical, and mechanical properties of composites. The disc-diffusion method showed pronounced antibacterial activity of BC composites against E. coli ATCC 25922 and S. aureus ATCC 25923.

Zeolitic imidazolate framework-8/bacterial cellulose composites for iodine loading and their antibacterial performance.

Bacterial cellulose (BC), produced by bacteria and fungi, is a promising material in the biomedical field. However, non-antibacterial activity limits its broad applications. Herein, antibacterial composites (BC/ZIF-8-iodine) were prepared by loading iodine into zeolitic imidazolate framework-8 (ZIF-8) modified BC (BC/ZIF-8). BC/ZIF-8-iodine was well characterized by SEM, XRD, FTIR, XPS, Raman and contact angle analyses. The increase of ZIF-8 content augmented the loading capacity of iodine in BC/ZIF-8-iodine. Meanwhile, the adsorbed iodine can be released from BC/ZIF-8-iodine composites, following the Higuchi equation. A reduced sublimation of iodine was observed in BC/ZIF-8-iodine composites, indicating their good iodine preservation ability. BC/ZIF-8-iodine composites exhibited strong antibacterial activity towards Escherichia coli, Staphylococcus aureus and Candida albicans. XPS and Raman analyses indicated that the adsorbed iodine of BC/ZIF-8-iodine composites was in the form of I3-. The expected iodine loading, release and preservation behaviors of BC/ZIF-8-iodine composites ensure their antibacterial performance and suggest potential clinical applications.

Bacterial cellulose as a potential biopolymer in biomedical applications: a state-of-the-art review.

Throughout history, natural biomaterials have benefited society. Nevertheless, in recent years, tailoring natural materials for diverse biomedical applications accompanied with sustainability has become the focus. With the progress in the field of materials science, novel approaches for the production, processing, and functionalization of biomaterials to obtain specific architectures have become achievable. This review highlights an immensely adaptable natural biomaterial, bacterial cellulose (BC). BC is an emerging sustainable biopolymer with immense potential in the biomedical field due to its unique physical properties such as flexibility, high porosity, good water holding capacity, and small size; chemical properties such as high crystallinity, foldability, high purity, high polymerization degree, and easy modification; and biological characteristics such as biodegradability, biocompatibility, excellent biological affinity, and non-biotoxicity. The structure of BC consists of glucose monomer units polymerized via cellulose synthase in β-1-4 glucan chains, creating BC nano fibrillar bundles with a uniaxial orientation. BC-based composites have been extensively investigated for diverse biomedical applications due to their similarity to the extracellular matrix structure. The recent progress in nanotechnology allows the further modification of BC, producing novel BC-based biomaterials for various applications. In this review, we strengthen the existing knowledge on the production of BC and BC composites and their unique properties, and highlight the most recent advances, focusing mainly on the delivery of active pharmaceutical compounds, tissue engineering, and wound healing. Further, we endeavor to present the challenges and prospects for BC-associated composites for their application in the biomedical field.