Antimicrobial Blue Light Research Articles

An antimicrobial blue light prototype device controls infected wounds in a preclinical porcine model.

We developed a translational prototype antimicrobial blue light (ABL) device for treating skin wounds with ABL. Partial-thickness surgical wounds were created in live swine, an animal whose skin is considered the most like human skin, then heavily contaminated and left untreated for 24 hours with methicillin-resistant Staphylococcus aureus (MRSA). ABL treatment stabilized and reduced MRSA infection by greater than four orders of magnitude (>99.99%; p<0.0001) compared with untreated wounds in the same animal, after only two daily treatments. These data support further development of such devices for controlling infection in skin wounds. ABL, with or without concomitant administration of negative pressure, antimicrobials, or photosensitizers, could play an important role in modern wound care by reducing the amount, duration, and cost of antibiotics needed, helping reduce AMR. No such device for treating human cutaneous wounds currently exists. This deserves further development and study.

Antimicrobial blue light inactivation of Pseudomonas aeruginosa: Unraveling the multifaceted impact of wavelength, growth stage, and medium composition

Pseudomonas aeruginosa, a notable pathogen frequently associated with hospital-acquired infections, displays diverse intrinsic and acquired antibiotic resistance mechanisms, posing a significant challenge in infection management. Antimicrobial blue light (aBL) has been demonstrated as a potential alternative for treating P. aeruginosa infections. In this study, we investigated the impact of blue light wavelength, bacterial growth stage, and growth medium composition on the efficacy of aBL. First, we compared the efficacy of light wavelengths 405 nm, 415 nm, and 470 nm in killing three multidrug resistant clinical strains of P. aeruginosa. The findings indicated considerably higher antibacterial efficacy for 405 nm and 415 nm wavelength compared to 470 nm. We then evaluated the impact of the bacterial growth stage on the efficacy of 405 nm light in killing P. aeruginosa using a reference strain PAO1 in exponential, transitional, or stationary phase. We found that bacteria in the exponential phase were the most susceptible to aBL, followed by the transitional phase, while those in the stationary phase exhibited the highest tolerance. Additionally, we quantified the production of reactive oxygen species (ROS) in bacteria using the 2′,7′-dichlorofluorescein diacetate (DCFH-DA) probe and flow cytometry, and observed a positive correlation between aBL efficacy and ROS production. Finally, we determined the influence of growth medium on aBL efficacy. PAO1 was cultivated in brain heart infusion (BHI), Luria-Bertani (LB) broth or Casamino acids (CAA) medium, before being irradiated with aBL at 405 nm. The CAA-grown bacteria exhibited the highest sensitivity to aBL, followed by those grown in LB broth, and the BHI-grown bacteria demonstrated the lowest sensitivity. By incorporating FeCl3, MnCl2, ZnCl2, or the iron chelator 2,2′-bipyridine (BIP) into specific media, we discovered that aBL efficacy was affected by the iron levels in culture media.

Could light be a broad-spectrum antimicrobial?

A review on antimicrobial resistance mechanisms discussing the main light-based antimicrobial approaches including ultraviolet light (UV), antimicrobial photodynamic therapy (aPDT), and antimicrobial blue light (aBL). To describe antimicrobial resistance mechanisms and to present potential light-based alternatives to conventional antimicrobials. The paper was divided into different topics, starting with an approach to antimicrobial resistance mechanisms. Subsequently, emphasis was placed on innovative light-based antimicrobials approaches, including aBL, UV, and aPDT. The review suggests that blue light (400-470 nm) acts on endogenous porphyrins with peak absorption at 405 nm, thus not requiring the administration of photosensitizers, to trigger antimicrobial effects. In this regarding, the direct effect of aBL could be attributed to both the generation of reactive oxygen species (ROS), which induces microbicidal effects, and the inactivation of bacterial defense mechanisms. In turn, blue light combined with curcumin has been used in the treatment of dental infections. Otherwise, green light (495-570 nm) associated with the photosensitizer Rose Bengal has shown promising results both in wound closure due to the induction of additional collagen cross-link formation and in reducing the viability of Pseudomonas aeruginosa. Red light (620-750 nm) is the wavelength most commonly used in aPDT, presenting superior tissue penetration capability compared to blue and green light. Both red and infrared light act directly as photobiomodulation agents, promoting tissue repair with greater penetration depth for the infrared spectrum. Conversely, red light combined with methylene blue is the most commonly used technique in the treatment of localized infections. Meanwhile, infrared light associated with indocyanine green acts as a photothermal and photosensitizing agent, promoting thermal damage and production of ROS. Ultraviolet lights UVA, UVB, and UVC (200-400 nm) have antimicrobial potential related to inducing changes in DNA and generating both ROS and singlet oxygen. Furthermore, light can enhance the efficacy of traditional antimicrobial agents by deactivating microbial resistance, both through increasing the permeability of the cell membrane and by inhibiting the efflux pump and β-lactamases of the bacteria. The antimicrobial potential of light is extensive; however, there is a limitation regarding the depth of penetration of certain wavelengths into infected areas. Furthermore, there is a need for additional studies to determine the safety and efficacy of various approaches using light at its different wavelengths.

Blue Light Compromises Bacterial β-Lactamases Activity to Overcome β-Lactam Resistance.

In this study, we evaluated the effectiveness of antimicrobial blue light (aBL; 410 nm wavelength) against β-lactamase-carrying bacteria and the effect of aBL on the activity of β-lactamases. Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae strains carrying β-lactamases as well as a purified β-lactamase enzymes were studied. β-lactamase activity was assessed using a chromogenic cephalosporin hydrolysis assay. Additionally, we evaluated the role of porphyrins in the photoreaction, as well as protein degradation by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Finally, we investigated the bactericidal effect of combined aBL-ceftazidime exposure against a metallo-β-lactamase expressing P. aeruginosa strain. Our study demonstrated that aBL effectively killed β-lactamase-producing bacteria and reduced β-lactamase activity. After an aBL exposure of 1.52 J/cm2, a 50% reduction in enzymatic activity was observed in P. aeruginosa. Additionally, we found a 40% decrease in the photoreaction activity of porphyrins following an aBL exposure of 64.8 J/cm2. We also revealed that aBL reduced β-lactamase activity via protein degradation (after 136.4 J/cm2). Additionally, aBL markedly improved the bactericidal effect of ceftazidime (by >4-log10) in the metallo-β-lactamase P. aeruginosa strain. Our results provide evidence that aBL compromises bacterial β-lactamase activity, offering a potential approach to overcome β-lactam resistance in bacteria.

High-Intensity Blue Light (450-460 nm) Phototherapy for Pseudomonas aeruginosa-Infected Wounds.

Background: Nosocomial wound infection with Pseudomonas aeruginosa (PA) is a serious complication often responsible for septic mortality of burn patients. High-intensity antimicrobial blue light (aBL) treatment may represent an alternative therapy for PA infections. Methods: Antibacterial effects of an light-emitting diode (LED) array (450-460 nm; 300 mW/cm2; 15/30 min; 270/540J/cm2) against PA were determined by suspension assay, biofilm assay, and a human skin wound model and compared with 15-min topically applied 3% citric acid (CA) and wound irrigation solution (Prontosan®; PRT). Results: The aBL reduced the bacterial number (2.51-3.56 log10 CFU/mL), whereas PRT or CA treatment achieved a 4.64 or 6.60 log10 CFU/mL reduction in suspension assays. The aBL reduced biofilm formation by 60%-66%. PRT or CA treatment showed reductions by 25% or 13%. In this study, aBL reduced bacterial number in biofilms (1.30-1.64 log10 CFU), but to a lower extent than PRT (2.41 log10 CFU) or CA (2.48 log10 CFU). In the wound skin model, aBL (2.21-2.33 log10 CFU) showed a bacterial reduction of the same magnitude as PRT (2.26 log10 CFU) and CA (2.30 log10 CFU). Conclusions: The aBL showed a significant antibacterial efficacy against PA and biofilm formation in a short time. However, a clinical application of aBL in wound therapy requires effective active skin cooling and eye protection, which in turn may limit clinical implementation.

High-Intensity Blue Light (450-460 nm) Phototherapy for Pseudomonas aeruginosa-Infected Wounds.

Background: Nosocomial wound infection with Pseudomonas aeruginosa (PA) is a serious complication often responsible for the septic mortality of burn patients. Objective: High-intensity antimicrobial blue light (aBL) treatment may represent an alternative therapy for PA infections and will be investigated in this study. Methods: Antibacterial effects of a light-emitting diode array (450-460 nm; 300 mW/cm2; 15/30 min; 270/540 J/cm2) against PA were determined by suspension assay, biofilm assay, and a human skin wound model and compared with 15-min topically applied 3% citric acid (CA) and wound irrigation solution (Prontosan®; PRT). Results: aBL reduced the bacterial number [2.51-3.56 log10 colony-forming unit (CFU)/mL], whereas PRT or CA treatment achieved a 4.64 or 6.60 log10 CFU/mL reduction in suspension assays. aBL reduced biofilm formation by 60-66%. PRT or CA treatment showed reductions by 25% or 13%. Here, aBL reduced bacterial number in biofilms (1.30-1.64 log10 CFU), but to a lower extend than PRT (2.41 log10 CFU) or CA (2.48 log10 CFU). In the wound skin model, aBL (2.21-2.33 log10 CFU) showed a bacterial reduction of the same magnitude as PRT (2.26 log10 CFU) and CA (2.30 log10 CFU). Conclusions: aBL showed a significant antibacterial efficacy against PA and biofilm formation in a short time. However, a clinical application of aBL in wound therapy requires effective active skin cooling and eye protection, which in turn may limit clinical implementation.

Sensitivity of Xylella fastidiosa subsp. pauca Salento-1 to light at 410 nm

All over the world, from America to the Mediterranean Sea, the plant pathogen Xylella fastidiosa represents one of the most difficult challenges with many implications at ecological, agricultural, and economic levels. X. fastidiosa is a rod-shaped Gram-negative bacterium belonging to the family of Xanthomonadaceae. It grows at very low rates and infects a wide range of plants thanks to different vectors. Insects, through their stylets, suck a sap rich in nutrients and inject bacteria into xylem vessels. Since, until now, no antimicrobial treatment has been successfully applied to kill X. fastidiosa and/or prevent its diffusion, in this study, antimicrobial blue light (aBL) was explored as a potential anti-Xylella tool. Xylella fastidiosa subsp. pauca Salento-1, chosen as a model strain, showed a certain degree of sensitivity to light at 410 nm. The killing effect was light dose dependent and bacterial concentration dependent. These preliminary results support the potential of blue light in decontamination of agricultural equipment and/or plant surface; however, further investigations are needed for in vivo applications.

Treatment of infected wounds by using antimicrobial blue light phototherapy

Treatment of infected wounds by using antimicrobial blue light phototherapy

Antimicrobial Blue Light (aBL) as a potential tool to reduce bacterial spoilage in the fishery chain

Along the fishery chain, a high amount of fish is lost for the activity of spoilage microorganisms originating from the environment, human handling and fish themselves. Different techniques are conventionally used to reduce the growth of bacteria: from cold temperature and icing to high concentration of salts, from drying to natural antimicrobial compounds. In this study, the antimicrobial Blue Light (aBL) was considered as an innovative tool. In particular, the irradiation with light at 410 nm inhibited the growth of most bacteria isolated from skin samples of anchovies and sardines chosen for their worldwide commercial importance. Bacterial strains showed a different sensitivity to light treatment: the ones isolated from anchovy were more sensitive than those from sardine. Investigations were performed on Aeromonas bestiarum, an emerging foodborne pathogen. Upon irradiation with light at 410 nm (200 J/cm2), a statistically significant decrease of 3 log units was observed. The same fluence rate successfully inhibited the biofilm formation of A. bestiarum, and disrupted 50 % of the adherent biomass of a 24-h old biofilm. The irradiation of Staphyococcus vitulinus compromised its viability and the associated proteolytic activity known to contribute to meat spoilage. In vivo experiments showed that aBL caused a remarkable decrease (at least 50 %) of viable counts of bacteria from anchovy and sardine skin samples conserved at 4 °C for one day. In conclusion, these results support the potential use of blue light in reducing the growth of skin microorganisms potentially responsible for loss of food safety, quality and decrease of storage life.

Can antimicrobial blue light contribute to resistance development? Genome-wide analysis revealed aBL-protective genes in Escherichia coli.

Increasing antibiotic resistance and the lack of new antibiotic-like compounds to combat bacterial resistance are significant problems of modern medicine. The development of new alternative therapeutic strategies is extremely important. Antimicrobial blue light (aBL) is an innovative approach to combat multidrug-resistant microorganisms. aBL has a multitarget mode of action; however, the full mechanism of aBL antibacterial action requires further investigation. In addition, the potential risk of resistance development to this treatment should be considered.

The influence of growth medium on the photodynamic susceptibility of Aggregatibacter actinomycetemcomitans to antimicrobial blue light.

The aim of this study was to investigate whether antimicrobial blue light (aBL) can cause the death of Aggregatibacter actinomycetemcomitans (A.a) and to determine the influence of different culture media, specifically brain heart infusion and blood agar, on bacterial survival fraction. An LED emitting at 403 ± 15nm, with a radiant power of 1W, irradiance of 588.2 mW/cm2, and an irradiation time of 0min, 1min, 5min, 10min, 30min, and 60min, was used. The plates were incubated in microaerophilic conditions at 37°C for 48h, and the colony-forming units were counted. The photosensitizers were investigated using spectroscopy and fluorescence microscopy. There was no significant difference between the culture media (p > 0.05). However, a statistical reduction in both media was observed at 30min (1058J/cm2) (p < 0.05). The findings of this study suggest that aBL has the potential to kill bacteria regardless of the culture media used. Light therapy could be a promising and cost-effective strategy for preventing periodontal disease when used in combination with mechanical plaque control.

Blue Light Potentiates Antibiotics in Bacteria via Parallel Pathways of Hydroxyl Radical Production and Enhanced Antibiotic Uptake.

In the age of antimicrobial resistance, the urgency by which novel therapeutic approaches need to be introduced into the clinical pipeline has reached critical levels. Antimicrobial blue light (aBL), as an alternative approach, has demonstrated promise as a stand-alone therapeutic method, albeit with a limited window of antimicrobial activity. Work by others indicates that treatment with antibiotics increases the production of reactive oxygen species (ROS) which may, in part, contribute to the bactericidal effects of antibiotics. These findings suggest that there may be potential for synergistic interactions with aBL, that similarly generates ROS. Therefore, in this study, the mechanism of aBL is investigated, and the potential for aBL to synergistically promote antibiotic activity is similarly evaluated. Furthermore, the translatability of using aBL and chloramphenicol in combination within a mouse model of Acinetobacter baumanii burn infection is assessed. It is concluded that porphyrins and hydroxyl radicals driven by "free iron" are paramount to the effectiveness of aBL; and aBL is effective at promoting multiple antibiotics in different multidrug-resistant bacteria. Moreover, rROS up-regulation, and promoted antibiotic uptake are observed during aBL+antibiotic exposure. Lastly, aBL combined with chloramphenicol appears to be both effective and safe for the treatment of A. baumannii burn infection. In conclusion, aBL may be a useful adjunct therapy to antibiotics to potentiate their action.

Photoinactivation of Escherichia coli by 405nm and 450nm light-emitting diodes: Comparison of continuous wave and pulsed light.

Antimicrobial blue light (ABL) therapy is one of the novel non-antibiotic approaches and recent studies showed the potential of pulsed ABL. Comparing photoinactivation effect of continuous wave (CW) and pulsed blue light and investigating the impact of varying light parameters. E. coli cells in planktonic were treated with CW and pulsed light (405nm and 450nm) at 60 mW/cm2, and the samples were taken to assess survival, reactive oxygen species (ROS) level, damage of cell membrane and metabolic activity. Further, a ROS scavenger was used to find the role of ROS played in ABL therapy. E. coli was more sensitive to 405nm light and the photoinactivation was dose-dependent. Pulsed 405nm light showed the better antimicrobial effect on E. coli and caused increasing damage of cell membrane. It might be attributed to the ROS production in bacteria. Pulsed light has a potential of improving the efficacy of ABL therapy and is worth to be explored deeply further.

Viricide activity of antimicrobial blue light (405 nm) against the SARS-CoV-2 and influenza virus

Abstract Background Over the years, antimicrobial blue light (aBL) at a 405 nm wavelength has emerged as a potential alternative treatment for reducing the environmental contamination. It is well accepted that aBL is much less detrimental to host cells than UV-C irradiation and can be used in the presence of people. This study aims to determine the viricide activity, against the SARS-CoV-2 and influenza virus types A and B, of the nUV-A radiation, using a customized nUV-A ceiling lamp System. Methods The experiment took place in March 2023. An nUV-A ceiling lamp prototype, composed of 9 LEDs at 405 nm, was fixed on a metal scaffold, on which the outline of a multiwell plate (24 wells) was traced to carry out the tests correctly. Each plate well was inoculated with 100 µL of SARS-CoV2 or influenza virus types A or B suspension. The multiwell plate was irradiated at 32 cm for 45 and 90 minutes, with an emitted energy dose of 12 J/cm2 and 24 J/cm2. Three samples were inoculated with viruses and subjected to the action of nUV-A as per protocol, and 3 samples were inoculated but not treated with nUV-A to determine viral titer after recovery and examined immediately after inoculation. The re-collected suspensions were used to inoculate a wells plate into which the VERO E6 cell cultures were fixed and then incubated for 3 days at 37° C. Results The results showed that after a 45 min exposition, the measurable log10 mean reduction was 1.50 for SARS-CoV2, 0.13 for influenza virus type A and 0.12 for type B; after 90 min the log10 mean reduction was 2.33 for SARS-CoV2, 0.16 for influenza virus type A and 0.17 for type B. Conclusions Tests have shown that aBL can be effective in reducing the viral load of the SARS-CoV2 virus and, to a lesser extent, the influenza A/B viruses. Disinfection with aBL appears effective and avoid the adverse effects of using UV-C. Further studies will evaluate how to improve the results on influenza viruses and the application on other viruses such as RSV. Key messages • NearUV-A lamp has proven to reduce the virucide activity of all viruses, more for sars-cov2. • Using aBL avoids the adverse UV-C’s effects.

Inactivation of dried cells and biofilms of Listeria monocytogenes by exposure to blue light at different wavelengths and the influence of surface materials.

Antimicrobial blue light (aBL) in the 400-470 nm wavelength range has been reported to kill multiple bacteria. This study assessed its potential for mitigating an important foodborne pathogen, Listeria monocytogenes (Lm), focusing on surface decontamination. Three wavelengths were tested, with gallic acid as a photosensitizing agent (Ps), against dried cells obtained from bacterial suspensions, and biofilms on stainless-steel (SS) coupons. Following aBL exposure, standard microbiological analysis of inoculated coupons was conducted to measure viability. Statistical analysis of variance was performed. Confocal laser scanning microscopy was used to observe the biofilm structures. Within 16 h of exposure at 405 nm, viable Lm dried cells and biofilms were reduced by approx. 3 log CFU/cm2 with doses of 2,672 J/cm2. Application of Ps resulted in an additional 1 log CFU/cm2 at 668 J/cm2, but its effect was not consistent. The highest dose (960 J/cm2) at 420 nm reduced viable counts on the biofilms by 1.9 log CFU/cm2. At 460 nm, after 800 J/cm2, biofilm counts were reduced by 1.6 log CFU/cm2. The effect of material composition on Lm viability was also investigated. Irradiation at 405 nm (668 J/cm2) of cells dried on polystyrene resulted in one of the largest viability reductions (4.0 log CFU/cm2), followed by high-density polyethylene (3.5 log CFU/cm2). Increasing the dose to 4,008 J/cm2 from 405 nm (24 h), improved its efficacy only on SS and polyvinyl chloride. Biofilm micrographs displayed a decrease in biofilm biomass due to the removal of biofilm portions from the surface and a shift from live to dead cells suggesting damage to biofilm cell membranes. These results suggest that aBL is a potential intervention to treat Lm contamination on typical material surfaces used in food production. IMPORTANCE Current cleaning and sanitation programs are often not capable of controlling pathogen biofilms on equipment surfaces, which transmit the bacteria to ready-to-eat foods. The presence of native plant microbiota and organic matter can protect pathogenic bacteria by reducing the efficacy of sanitizers as well as promoting biofilm formation. Post-operation washing and sanitizing of produce contact surfaces might not be adequate in eliminating the presence of pathogens and commensal bacteria. The use of a dynamic and harmless light technology during downtime and close of operation could serve as a useful tool in preventing biofilm formation and persistence. Antimicrobial blue light (aBL) technology has been explored for hospital disinfection with very promising results, but its application to control foodborne pathogens remains relatively limited. The use of aBL could be a complementary strategy to inactivate surfaces in restaurant or supermarket deli settings.

Antibiotic resistances from slaughterhouse effluents and enhanced antimicrobial blue light technology for wastewater decontamionation

The frequencies of 6 different facultative pathogenic bacteria of the ESKAPE group (priority list WHO) and a total of 14 antibiotic resistance genes (ARGs) with different priorities for human medicine were quantified in wastewaters of poultry and pig slaughterhouses using molecular biological approaches. Raw sewage from poultry and pig slaughterhouses was found to be contaminated not only with facultative pathogenic bacteria but also with various categories of clinically relevant ARGs, including ARGs against the reserve antibiotics group. The concentration of the different gene targets decreased after on-site conventional biological or advanced oxidative wastewater treatments, but was not eliminated. Hence, the antimicrobial BlueLight (aBL) in combination with a porphyrin photo-sensitizer was studied with ESKAPE bacteria and real slaughterhouse wastewaters. The applied broad LED-based blue light (420–480 nm) resulted in groups of sensitive, intermediate, and non-sensitive ESKAPE bacteria. The killing effect of aBL was increased in the non-sensitive bacteria Klebsiella pneumoniae and Enterococcus faecium due to the addition of porphyrins in concentrations of 10−6 M. Diluted slaughterhouse raw wastewater was treated with broad spectrum aBL and in combination with porphyrin. Here, the presence of the photo-sensitizer enhanced the aBL biocidal impact.

Photoinactivation and Photoablation of Porphyromonas gingivalis.

Several types of phototherapy target human pathogens and Porphyromonas gingivitis (Pg) in particular. The various approaches can be organized into five different treatment modes sorted by different power densities, interaction times, effective wavelengths and mechanisms of action. Mode 1: antimicrobial ultraviolet (aUV); mode 2: antimicrobial blue light (aBL); mode 3: antimicrobial selective photothermolysis (aSP); mode 4: antimicrobial vaporization; mode 5: antimicrobial photodynamic therapy (aPDT). This report reviews the literature to identify for each mode (a) the putative molecular mechanism of action; (b) the effective wavelength range and penetration depth; (c) selectivity; (d) in vitro outcomes; and (e) clinical trial/study outcomes as these elements apply to Porphyromonas gingivalis (Pg). The characteristics of each mode influence how each is translated into the clinic.

Antimicrobial Resistance: Is There a 'Light' at the End of the Tunnel?

In recent years, with the increases in microorganisms that express a multitude of antimicrobial resistance (AMR) mechanisms, the threat of antimicrobial resistance in the global population has reached critical levels. The introduction of the COVID-19 pandemic has further contributed to the influx of infections caused by multidrug-resistant organisms (MDROs), which has placed significant pressure on healthcare systems. For over a century, the potential for light-based approaches targeted at combatting both cancer and infectious diseases has been proposed. They offer effective killing of microbial pathogens, regardless of AMR status, and have not typically been associated with high propensities of resistance development. To that end, the goal of this review is to describe the different mechanisms that drive AMR, including intrinsic, phenotypic, and acquired resistance mechanisms. Additionally, the different light-based approaches, including antimicrobial photodynamic therapy (aPDT), antimicrobial blue light (aBL), and ultraviolet (UV) light, will be discussed as potential alternatives or adjunct therapies with conventional antimicrobials. Lastly, we will evaluate the feasibility and requirements associated with integration of light-based approaches into the clinical pipeline.

An Approach to Improve Energy Efficiency during Antimicrobial Blue Light Inactivation: Application of Pulse-Width Modulation Dimming to Balance Irradiance and Irradiation Time.

Antimicrobial blue light (aBL) is an effective non-destructive inactivation technique and has received increasing attention. Despite its significance, the existing research has not thoroughly delved into the impacts of irradiance and irradiation time on enhancing energy efficiency during aBL inactivation and the explanation of the enhancement effect of pulse exposure. In this paper, a series of Escherichia coli inactivation experiments with different duty cycles, pulse frequencies, and irradiation times were conducted, and the relative concentrations of reactive oxygen species (ROS) were measured under corresponding conditions. A two-dimensional (2-D) Hom model was proposed to evaluate the effect of irradiance and irradiation time. The results show that, compared to continuous exposure, pulsed aBL (duty cycle = 25%) can save ~37% of the energy to achieve the same inactivation effect and generate a 1.95 times higher ROS concentration. The 2-D Hom model obtains the optimal combination of average irradiance and time according to the desired reduction and shows that the irradiation time has a higher weight than the irradiance (1.677 and 1.083, respectively). Therefore, using pulse exposure with a lower average irradiance for a longer period of time can achieve a better inactivation effect when consuming equivalent energy. The proposed pulse-width modulation dimming approach helps promote the application of the aBL technique.

An antimicrobial blue light device to manage infection at the skin-implant interface of percutaneous osseointegrated implants.

Antimicrobial blue light (aBL) is an attractive option for managing biofilm burden at the skin-implant interface of percutaneous osseointegrated (OI) implants. However, marketed aBL devices have both structural and optical limitations that prevent them from being used in an OI implant environment. They must be handheld, preventing even irradiation of the entire skin-implant interface, and the devices do not offer sufficient optical power outputs required to kill biofilms. We present the developmental process of a unique aBL device that overcomes these limitations. Four prototypes are detailed, each being a progressive improvement from the previous iteration as we move from proof-of-concept to in vivo application. Design features focused on a cooling system, LED orientation, modularity, and "sheep-proofing". The final prototype was tested in an in vivo OI implant sheep model, demonstrating that it was structurally and optically adequate to address biofilm burdens at the skin-implant of percutaneous OI implants. The device made it possible to test aBL in the unique OI implant environment and compare its efficacy to clinical antibiotics-data which had not before been achievable. It has provided insight into whether or not continued pursual of light therapy research for OI implants, and other percutaneous devices, is worthwhile. However, the device has drawbacks concerning the cooling system, complexity, and size if it is to be translated to human clinical trials. Overall, we successfully developed a device to test aBL therapy for patients with OI implants and helped progress understanding in the field of infection management strategies.