Long-term Biofilm Research Articles

Preventing bacterial adhesion on scaffolds for bone tissue engineering

Bone implant infection constitutes a major sanitary concern which is associated to high morbidity and health costs. This manuscript focused on overviewing the main research efforts committed up to date to develop innovative alternatives to conventional treatments, such as those with antibiotics. These strategies mainly rely on chemical modifications of the surface of biomaterials, such as providing it of zwitterionic nature, and tailoring the nanostructure surface of metal implants. These surface modifications have successfully allowed inhibition of bacterial adhesion, which is the first step to implant infection, and preventing long-term biofilm formation compared to pristine materials. These strategies could be easily applied to provide three-dimensional (3D) scaffolds based on bioceramics and metals, of which its manufacture using rapid prototyping techniques was reviewed. This opens the gates for the design and development of advanced 3D scaffolds for bone tissue engineering to prevent bone implant infections.

Long-term influences of pipe materials on bacterial communities of matured biofilms (> 40 years’ old) in drinking water distribution systems

Pipe materials appear to play an important role in the development of biofilms in drinking water distribution systems. However, there is controversy as to whether pipe materials shape the composition and diversity of bacterial communities in biofilms. To investigate the long-term effects of pipe materials on biofilms, triplicate samples of mature biofilms on unplasticized polyvinyl chloride (PVC-U), grey cast iron and asbestos cement (pipe age > 40 years) were obtained from three areas of an unchlorinated drinking water distribution system in the Netherlands. Illumina sequencing was performed and 773 OTUs (730 OTUs-814 OTUs) were detected within the biofilms on the three pipe materials, all of which were dominated by Proteobacteria (36.2%-46.1%). Both the alpha and beta diversity results showed that the bacterial communities of the biofilms formed on different pipe materials were highly similar. The neutral community model revealed that the assembly of the biofilm communities was governed by environmental selection rather than neutral processes. Among the 142 shared OTUs between the water and biofilm samples, there were 25 enriched OTUs (e.g., OTU7, assigned as Nitrospira spp.), which accounted for 62.6% of the total sequences, while 16 OTUs were disadvantaged (e.g., OTU14 and OTU40, assigned as Hyphomicrobiaceae), accounting for 2.2% of the sequences. Based on the findings, we propose and discuss a harmonisation process by which biofilms with significant differences due to the pipe material harmonize over time resulting in biofilms with similar bacterial communities. Our findings provide valuable insights into long-term biofilm development, bridging an essential gap in our current understanding of the influence of pipe materials on biofilm communities. These findings also highlight the importance of long-term studies and point to a potentially masked harmonizing process during biofilm development over years/decades.

Sustainable Biofilm Inhibition Using Chitosan-Mesoporous Nanoparticle-Based Hybrid Slippery Composites.

In recent decades, extensive research has been directed toward mitigating microbial contamination and preventing biofilm formation. However, many conventional antibiofilm methods rely on hazardous and toxic substances, neglecting potential risks to human health and the environment. Moreover, these approaches often rely on single-strategy mechanisms, utilizing either bactericidal or fouling-resistant agents, which have shown limited efficacy in long-term biofilm suppression. In this study, we propose an efficient and sustainable biofilm-resistant slippery hybrid slippery composite. This composite integrates nontoxic and environmentally friendly materials including chitosan, silicone oil-infused polydimethylsiloxane, and mesoporous silica nanoparticles in a synergistic manner. Leveraging the bacteria-killing properties of chitosan and the antifouling capabilities of the silicone oil layer, the hybrid composite exhibits robust antibiofilm performance against both Gram-positive and Gram-negative bacteria. Furthermore, the inclusion of mesoporous silica nanoparticles enhances the oil absorption capacity and self-replenishing properties, ensuring exceptional biofilm inhibition even under harsh conditions such as exposure to high shear flow and prolonged incubation (7 days). This approach offers promising prospects for developing effective biofilm-resistant materials with a reduced environmental impact and improved long-term performance.

The dynamics of bacterial proliferation, viability, and extracellular polymeric substances in oral biofilm development

ObjectivesThis study investigated the relationship between bacterial growth, viability, and extracellular polymeric substances (EPS) formation in biofilms, particularly regarding resistance development. It also examined the impact of chemical factors on the EPS matrix and bacterial proliferation in oral biofilms. MethodsThree multi-species oral biofilms were incubated in anaerobic conditions. Three strains of Enterococcus faecalis were incubated in aerobic conditions. The incubation periods ranged from 0 h to 7 days for short-term biofilms, and from 3 to 90 days for long-term biofilms. Fluorescent labeling with carboxyfluorescein diacetate succinimidyl ester (CFSE) and flow cytometry were used to track EPS and bacterial growth. Confocal laser scanning microscopy (CLSM) assessed bacterial viability and EPS structure. Biofilms aged 7, 14, and 21 days were treated with 2 % chlorhexidine (CHX) and 1 % sodium hypochlorite (NaOCl) to evaluate their effects on EPS and bacterial proliferation. ResultsShort-term biofilms showed rapid bacterial proliferation and a gradual increase in EPS, maintaining stable viability. In the first two weeks, a significant rise in CFSE indicated growing maturity. From 14 to 90 days, EPS and CFSE levels stabilized. Following treatment, CHX significantly reduced bacterial proliferation, while NaOCl decreased EPS volume. ConclusionsBiofilm development involves a balance between bacterial proliferation and EPS production. The complexity of this process poses challenges in treating biofilm-associated infections, requiring strategies tailored to the biofilm's developmental stage. Clinical significanceFor effective root canal treatment, it is imperative to focus on reducing bacterial proliferation during the early stages of oral infections. In contrast, strategies aimed at minimizing EPS production could be more beneficial for long-term management of these conditions.

Sustainable Janus lignin-based polyurethane biofoams with robust antibacterial activity and long-term biofilm resistance

Conventional antibiotic therapies have been becoming less efficient due to increasingly, and sometimes fully, antibiotic-resistant bacterial strains, sometimes known as “superbacteria” or “superbugs.” Thus, novel antibacterial materials to effectively inhibit or kill bacteria are crucial for humanity. As a broad-spectrum antimicrobial agent, silver nanoparticles (Ag NPs) have been the most widely commercialized of biomedical materials. However, long-term use of significant amounts of Ag NPs can be potentially harmful to human health through a condition known as argyria, in addition to being toxic to many environmental systems. It is, thus, highly necessary to reduce the amount of Ag NPs employed in medical treatments while also ensuring maintenance of antimicrobial properties, in addition to reducing the overall cost of treatment for humanitarian utilization. For this purpose, naturally sourced antimicrobial polylysine (PL) is used to partially replace Ag NPs within the materials composition. Accordingly, a series of PL, Ag NPs, and lignin-based polyurethane (LPU) composite biofoams (LPU-PL-Ag) were prepared. These proposed composite biofoams, containing at most only 2 % PL and 0.03 % Ag NPs, significantly inhibited the growth of both Gram-positive and Gram-negative bacteria within 1 h and caused irreversibly destructive bactericidal effects. Additionally, with a layer of polydimethylsiloxane (PDMS) on the surface, PDMS-LPU-PL(2 %)-Ag(0.03 %) can effectively prevent bacterial adhesion with a clearance rate of about 70 % for both bacterial biofilms within three days and a growth rate of more than 80 % for mouse fibroblasts NIH 3 T3. These lignin-based polyurethane biofoam dressings, with shorter antiseptic sterilization times and broad-spectrum antibacterial effects, are extremely advantageous for infected wound treatment and healing in clinical use.

Long-term performance and biofilms of the novel nano manganese dioxide coupling carbon source pre-loaded biological activated carbon filters for drinking water

In order to accelerate the start-up of biological activated carbon (BAC) filters and enhance ammonium (NH4+-N) removal performance, three substrates (sucrose and/or nano manganese dioxide (nMnO2)) pre-loaded BAC filters were set up to investigate the pollutants removals and microbiological characteristics for a long-term operation of 197 days. The average NH4+-N removal performance treated by the sucrose coupled with nMnO2 loaded BAC filter was the highest (71.18 %), which was 3.83 times of that by the control filter (18.58 %). 29 % of NH4+-N treated by the sucrose coupled with nMnO2 loaded BAC removed through the traditional nitrification and denitrification, or simultaneous nitrification and denitrification (SND) pathways according to the calculation of the alkalinity consumption (6.12 mmol/L). There was no leakage of carbon source and Mn, and no accumulation of nitrite from the substrates loaded BAC. The dominant bacteria in the sucrose coupled with nMnO2 loaded BAC were Dechloromona (accounting for 8.02% of the total bacterial) and Acidaminobacter (accounting for 15.16% of total bacterial) on the Day 180, which had the capacity of nitrification or denitrification. NH4+-N and micropollutants removals treated by the combined process of peracetic acid (PAA) pre-oxidation and substrates loaded BAC were significant due to the generation of assimilable organic carbon (AOC) (5.98 ± 1.93 μg-C/mL) by PAA (100 μM)/Fe2+ pre-oxidation and the higher biomass ((4.57 ± 3.07) × 107 cells/g DW BAC) in the sucrose coupled with nMnO2 loaded BAC filter. Therefore, nMnO2 coupling carbon source pre-loading strategy could not only enhance initial colonization, but also promote pollutants removals for long-term operation.

Contrasting genes conferring short- and long-term biofilm adaptation in Listeria.

Listeria monocytogenes is an opportunistic food-borne bacterium that is capable of infecting humans with high rates of hospitalization and mortality. Natural populations are genotypically and phenotypically variable, with some lineages being responsible for most human infections. The success of L. monocytogenes is linked to its capacity to persist on food and in the environment. Biofilms are an important feature that allow these bacteria to persist and infect humans, so understanding the genetic basis of biofilm formation is key to understanding transmission. We sought to investigate the biofilm-forming ability of L. monocytogenes by identifying genetic variation that underlies biofilm formation in natural populations using genome-wide association studies (GWAS). Changes in gene expression of specific strains during biofilm formation were then investigated using RNA sequencing (RNA-seq). Genetic variation associated with enhanced biofilm formation was identified in 273 genes by GWAS and differential expression in 220 genes by RNA-seq. Statistical analyses show that the number of overlapping genes flagged by either type of experiment is less than expected by random sampling. This novel finding is consistent with an evolutionary scenario where rapid adaptation is driven by variation in gene expression of pioneer genes, and this is followed by slower adaptation driven by nucleotide changes within the core genome.

Effect of Hydrogen Peroxide on Cyanobacterial Biofilms.

Although a range of disinfecting formulations is commercially available, hydrogen peroxide is one of the safest chemical agents used for disinfection in aquatic environments. However, its effect on cyanobacterial biofilms is poorly investigated. In this work, biofilm formation by two filamentous cyanobacterial strains was evaluated over seven weeks on two surfaces commonly used in marine environments: glass and silicone-based paint (Sil-Ref) under controlled hydrodynamic conditions. After seven weeks, the biofilms were treated with a solution of hydrogen peroxide (H2O2) to assess if disinfection could affect long-term biofilm development. The cyanobacterial biofilms appeared to be tolerant to H2O2 treatment, and two weeks after treatment, the biofilms that developed on glass by one of the strains presented higher biomass amounts than the untreated biofilms. This result emphasizes the need to correctly evaluate the efficiency of disinfection in cyanobacterial biofilms, including assessing the possible consequences of inefficient disinfection on the regrowth of these biofilms.

Evaluating scaling of capillary photo-biofilm reactors for high cell density cultivation of mixed trophies artificial microbial consortia.

Capillary biofilm reactors (CBRs) are attractive for growing photoautotrophic bacteria as they allow high cell-density cultivation. Here, we evaluated the CBR system's suitability to grow an artificial consortium composed of Synechocystis sp. PCC 6803 and Pseudomonas sp. VBL120. The impact of reactor material, flow rate, pH, O2, and medium composition on biomass development and long-term biofilm stability at different reactor scales was studied. Silicone was superior over other materials like glass or PVC due to its excellent O2 permeability. High flow rates of 520μLmin-1 prevented biofilm sloughing in 1m capillary reactors, leading to a 54% higher biomass dry weight combined with the lowest O2 concentration inside the reactor compared to standard operating conditions. Further increase in reactor length to 5m revealed a limitation in trace elements. Increasing trace elements by a factor of five allowed for complete surface coverage with a biomass dry weight of 36.8gm-2 and, thus, a successful CBR scale-up by a factor of 25. Practical application: Cyanobacteria use light energy to upgrade CO2, thereby holding the potential for carbon-neutral production processes. One of the persisting challenges is low cell density due to light limitations and O2 accumulation often occurring in established flat panel or tubular photobioreactors. Compared to planktonic cultures, much higher cell densities (factor 10 to 100) can be obtained in cyanobacterial biofilms. The capillary biofilm reactor (CBR) offers good growth conditions for cyanobacterial biofilms, but its applicability has been shown only on the laboratory scale. Here, a first scale-up study based on sizing up was performed, testing the feasibility of this system for large-scale applications. We demonstrate that by optimizing nutrient supply and flow conditions, the system could be enlarged by factor 25 by enhancing the length of the reactor. This reactor concept, combined with cyanobacterial biofilms and numbering up, holds the potential to be applied as a flexible, carbon-neutral production platform for value-added compounds.

Swine Model of Biofilm Infection and Invisible Wounds.

Biofilm infection is a major contributor to wound chronicity. The establishment of clinically relevant experimental wound biofilm infection requires the involvement of the host immune system. Iterative changes in the host and pathogen during the formation of such clinically relevant biofilm can only occur in vivo. The swine wound model is recognized for its advantages as a powerful pre-clinical model. There are several reported approaches for studying wound biofilms. In vitro and ex vivo systems are deficient in terms of the host immune response. Short-term in vivo studies involve acute responses and, thus, do not allow for biofilm maturation, as is known to occur clinically. The first long-term swine wound biofilm study was reported in 2014. The study recognized that biofilm-infected wounds may close as determined by planimetry, but the skin barrier function of the affected site may fail to be restored. Later, this observation was validated clinically. The concept of functional wound closure was thus born. Wounds closed but deficient in skin barrier function may be viewed as invisible wounds. In this work, we seek to report the methodological details necessary to reproduce the long-term swine model of biofilm-infected severe burn injury, which is clinically relevant and has translational value. This protocol provides detailed guidance on establishing an 8 week wound biofilm infection using P. aeruginosa (PA01). Eight full-thickness burn wounds were created symmetrically on the dorsum of domestic white pigs, which were inoculated with (PA01) at day 3 post-burn; subsequently, noninvasive assessments of the wound healing were conducted at different time points using laser speckle imaging (LSI), high-resolution ultrasound (HUSD), and transepidermal water loss (TEWL). The inoculated burn wounds were covered with a four-layer dressing. Biofilms, as established and confirmed structurally by SEM at day 7 post-inoculation, compromised the functional wound closure. Such an adverse outcome is subject to reversal in response to appropriate interventions.

Development of an In Vitro Model of the Gut Microbiota Enriched in Mucus-Adhering Bacteria.

Culturing the gut microbiota in in vitro models that mimic the intestinal environment is increasingly becoming a promising alternative approach to study microbial dynamics and the effect of perturbations on the gut community. Since the mucus-associated microbial populations in the human intestine differ in composition and functions from their luminal counterpart, we attempted to reproduce in vitro the microbial consortia adhering to mucus using an already established three-dimensional model of the human gut microbiota. Electrospun gelatin structures supplemented or not with mucins were inoculated with fecal samples and compared for their ability to support microbial adhesion and growth over time, as well as to shape the composition of the colonizing communities. Both scaffolds allowed the establishment of long-term stable biofilms with comparable total bacterial loads and biodiversity. However, mucin-coated structures harbored microbial consortia especially enriched in Akkermansia, Lactobacillus, and Faecalibacterium, being therefore able to select for microorganisms commonly considered mucosa-associated in vivo. IMPORTANCE These findings highlight the importance of mucins in shaping intestinal microbial communities, even those in artificial gut microbiota systems. We propose our in vitro model based on mucin-coated electrospun gelatin structures as a valid device for studies evaluating the effects of exogenous factors (nutrients, probiotics, infectious agents, and drugs) on mucus-adhering microbial communities.

Biofilm formation under food-relevant conditions and sanitizers' tolerance of a Pseudomonas fluorescens group strain.

The aim of this study was to determine the biofilm-forming ability of a strain belonging to the Pseudomonas fluorescens group isolated from the dairy environment under food-relevant conditions. Moreover, the effects of commercial sanitizers against preformed biofilms were assessed both in terms of viability and structure. The biofilms were formed on polystyrene, stainless steel (SS), and polytetrafluoroethylene (PTFE) in a wide range of temperatures (4-25°C) and were subjected to the action of 10 different sanitizers. The strain under study showed to be a strong biofilm-former regardless of temperature, particularly on polystyrene. The biofilms were mostly sensitive to chlorine and peracetic acid-based sanitizers. For some sanitizers (e.g. amphoteric), a relationship was observed between the material and the tolerance, while the temperature was not statistically significant. The formation of long-term biofilms on SS was also structurally affected by the temperature, showing microcolonies more irregular in shape and with lower cellularity at 4°C compared to 15°C, where the biofilm was more compact and with a high presence of EPS. The strain belonging to the P. fluorescens group was shown to quickly adhere and form mature biofilm at temperatures and on materials relevant to the food sector; however, biofilms formed under different conditions were differently tolerant to disinfectants. Findings from this study could provide a basis for developing targeted sanitation protocols in food plants.

Ultraviolet control of bacterial biofilms in microfluidic chips.

Polydimethylsiloxane (PDMS) microfluidic systems have been instrumental in better understanding couplings between physical mechanisms and bacterial biofilm processes, such as hydrodynamic effects. However, precise control of the growth conditions, for example, the initial distribution of cells on the substrate or the boundary conditions in a flow system, has remained challenging. Furthermore, undesired bacterial colonization in crucial parts of the systems, in particular, in mixing zones or tubing, is an important factor that strongly limits the duration of the experiments and, therefore, impedes our ability to study the biophysics of biofilm evolving over long periods of time, as found in the environment, in engineering, or in medicine. Here, we develop a new approach that uses ultraviolet-C (UV-C) light-emitting diodes (LEDs) to confine bacterial development to specific zones of interest in the flow channels. The LEDs are integrated into a 3D printed light guide that is positioned upon the chip and used to irradiate germicidal UV-C directly through the PDMS. We first demonstrate that this system is successful in controlling undesired growth of Pseudomonas aeruginosa biofilm in inlet and outlet mixing zones during 48 h. We further illustrate how this can be used to define the initial distribution of bacteria to perturb already formed biofilms during an experiment and to control colonization for seven days-and possibly longer periods of time-therefore opening the way toward long-term biofilm experiments in microfluidic devices. Our approach is easily generalizable to existing devices at low cost and may, thus, become a standard in biofilm experiments in PDMS microfluidics.

Expression of concern: Bacterial self-defense antibiotics release from organic-inorganic hybrid multilayer films for long-term anti-adhesion and biofilm inhibition properties.

Expression of concern for 'Bacterial self-defense antibiotics release from organic-inorganic hybrid multilayer films for long-term anti-adhesion and biofilm inhibition properties' by Qingwen Xu, Nanoscale, 2017, 9, 19245-19254, https://doi.org/10.1039/C7NR07106J.

Computational Design of Antimicrobial Active Surfaces via Automated Bayesian Optimization.

Biofilms pose significant problems for engineers in diverse fields, such as marine science, bioenergy, and biomedicine, where effective biofilm control is a long-term goal. The adhesion and surface mechanics of biofilms play crucial roles in generating and removing biofilm. Designing customized nanosurfaces with different surface topologies can alter the adhesive properties to remove biofilms more easily and greatly improve long-term biofilm control. To rapidly design such topologies, we employ individual-based modeling and Bayesian optimization to automate the design process and generate different active surfaces for effective biofilm removal. Our framework successfully generated optimized functional nanosurfaces for improved biofilm removal through applied shear and vibration. Densely distributed short pillar topography is the optimal geometry to prevent biofilm formation. Under fluidic shearing, the optimal topography is to sparsely distribute tall, slim, pillar-like structures. When subjected to either vertical or lateral vibrations, thick trapezoidal cones are found to be optimal. Optimizing the vibrational loading indicates a small vibration magnitude with relatively low frequencies is more efficient in removing biofilm. Our results provide insights into various engineering fields that require surface-mediated biofilm control. Our framework can also be applied to more general materials design and optimization.

A new plate-hanging method for biofilm quantification and its application to evaluate the role of surface hydrophobicity

A novel procedure for the quantitative analysis of biofilm formation by bacteria and yeasts, the Plate-hanging method, was developed. In this system, various polymer disks were hung from the lid of a 6-well plate, immersed in a cell suspension, and moderately shaken (70 rpm). In order to verify the validity of the procedure, the effects of the solid surface hydrophobicity of the test disks and the cell surface hydrophobicities of microorganisms on biofilm formation were investigated. Biofilm formation of bacteria and yeasts on the solid surface strongly depended on hydrophobic interactions between the solid surface and the cell surface. A positive correlation between the hydrophobic properties of substratum and cell surfaces was observed. On the other hand, hydrophilic yeasts preferentially adsorbed onto relatively hydrophilic surfaces. Moreover, the plate-hanging method coupled with the periodic exchange of the liquid medium enabled the quantification of long-term biofilm growth.

Chitosan/starch beads as bioinoculants carrier: long-term survival of bacteria and plant growth promotion.

Immobilization of microorganisms in biodegradable polymeric matrices constitutes a promising technology for plant growth promoting to overcome the challenging conditions of the rhizosphere. Previously, we demonstrated that beads prepared from blends of chitosan/starch of analytical grades ionically cross-linked are useful carriers for Azospirillum brasilense and Pseudomonas fluorescens. The aims of this work were to study A. brasilense Az39 and P. fluorescens ZME4 immobilization in industrial quality beads produced with a blend of chitosan/starch, to assess bacterial survival during long-term storage and biofilm distribution in the beads. We also proposed to analyze the consortia root colonization and its performance as plant growth-promoting bioinoculants compared to liquid counterpart. Our results revealed that A. brasilense Az39 and P. fluorescens ZME4 can coexist in industrial grade chitosan/starch beads, and this mixed immobilization benefits the survival rates of both species, even for more than a year under shelf storage. Confocal laser scanning microscopy with fluorescent dyed strains showed that both species remain mainly in different locations inside and over the beads. Additionally, maize seed treatment with beads-loaded bacteria resulted in growth promotion of roots in a similar manner than traditional liquid-based inoculation. The evidence collected here demonstrate that low-cost chitosan/starch beads are a suitable carrier for bacteria consortia and could be a reliable alternative to liquid inoculation in agronomic practices with additional benefits for industrial management. KEY POINTS: • Mixed immobilization increases bacterial survival in chitosan/starch industrial beads • Beads increase competence of bacteria in rhizosphere of maize • Inoculation mediated by beads promotes plant growth of maize.

Connecting environmental and evolutionary microbiology for the development of new agrobiotechnological tools.

Connecting environmental and evolutionary microbiology for the development of new agrobiotechnological tools.

Novel Extrapolymeric Substances Biocoating on Polyvinylidene Fluoride Membrane for Enhanced Attached Growth of Navicula incerta.

Cell adhesion is always the first step in biofilm development. With the emergence of attached cultivation systems, this study aims to promote a cost-effective approach for sustainable cultivation of microalgae, Navicula incerta, by pre-coating the main substrates, commercial polyvinylidene fluoride (PVDF) membranes with its own washed algal cells and self-produced soluble extracellular polymeric substances (EPS) for strengthened biofilm development. The effects of pH value (6 to 9), cell suspension volume (10 to 30mL), and EPS volume (10 to 50mL) were statistically optimized by means of response surface methodology toolkit. Model outputs revealed good agreement with cell adhesion data variation less than 1% at optimized pre-coating conditions (7.20 pH, 30mL cell suspension volume, and 50mL EPS volume). Throughout long-term biofilm cultivation, results demonstrated that EPS pre-coating substantially improved the attached microalgae density by as high as 271% than pristine PVDF due to rougher surface and the presence of sticky exopolymer particles. Nutrients absorbed via the available EPS coating from the bulk medium made the immobilized cells to release less polysaccharides on an average of 30% less than uncoated PVDF. This work suggests that adhesive polymer binders derived from organic sources can be effectively integrated into the development of high-performance novel materials as biocoating for immobilized microalgae cultivation.

Vitamin C and its therapeutic potential in the management of COVID19.

COVID19 has emerged as one of the worst pandemics in the history of mankind. Several vaccines have been approved by different government agencies worldwide, but data on their efficacy and safety are limited, and distribution remains a massive challenge. As per WHO, personal immunity is vital for protection against COVID19. Earlier, Vitamin C-mediated pathways have been shown to play critical role in boosting immunity attributed to its antioxidant properties. Recently, the involvement of such pathways in protection against COVID19 has been suggested. The controlled doses of Vitamin C administered through intravenous (IV) injections are being studied for determining its role in the prognosis of COVID19. In this article, we have discussed the potential role of Vitamin C in the management in COVID19 patients and presented recent clinical trials data. Additionally, we have elaborated the possibility of administering Vitamin C through inhalers in order to achieve local high concentration and the challenges of such approach.