Hydrogel Smart Bandage as a Diagnostic Tool for Infection in Burn Wounds

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Every year, almost half a million people are admitted to the emergency room because of burn wounds. Of the thousands of deaths that result from these wounds, more than half are due to complications from infection. An easy solution would be to administer antibiotics immediately, but this can lead to serious problems. When antibiotics are given, the majority of bacteria die, but a few with natural resistances may survive. These cells will eventually grow and reproduce, leading to the formation of bacterial cell lines that are resistant to current antibiotics. Currently, detection of infection requires evaluation by a medical professional to avoid taking antibiotics unnecessarily. Unfortunately, this method is very time consuming and may take several days to obtain test results such as blood or bacterial cultures. This option also may not be accessible in developing countries. Since infection can be fatal, it is beneficial to have a way to determine if a wound is infected without the need to visit a doctor and wait for test results. Here, we describe a smart hydrogel bandage that is able to detect when a burn wound has become infected. We chose to model a hydrogel bandage designed by SmartWound PREDICT using COMSOL, a finite element analysis simulation software. This bandage consists of a thin block of agarose hydrogel. This block contains wells that hold lipid vesicles full of fluorescent dye. The dye is self-quenching, meaning that the dye will not fluoresce while it is present in large concentrations within the minute volume of the vesicle. Once the vesicles rupture, the concentration will decrease as the dye exits the vesicle, allowing the dye to fluoresce. After a burn wound has occurred, the hydrogel bandage is placed over it. When the wound becomes colonized by bacteria (such that the immune system alone is insufficient in fending off the infection and medical intervention is required), the bacteria begin producing the pore-forming toxin alpha hemolysin (⍺-H). This toxin diffuses up through the bottom of the bandage and into the vesicle-containing wells. Upon contact with the ⍺-H, the vesicles will lyse and release the dye, which will begin to fluoresce in the presence of UV light. The fluorescence will signify that the wound has become infected and that the wearer should seek medical treatment. Our model investigates potential methods to minimize the time for fluorescent dye to be released after infection and maximize the time before the dye comes into contact with the skin. We want to be able to detect the presence of an infection quickly without allowing the dye to contaminate the wound. Because the safety data sheet recommends washing skin thoroughly with soap and water upon contact with the dye, we hope to minimize skin contact with the dye in our design. We based our bandage design on the preexisting bandage designed by SmartWound. To validate our model, we compared our COMSOL model results to the results obtained with the SmartWound PREDICT bandage. We found that our bandage exhibited visible fluorescence after 4 hours, like theirs did. We also found a similar dye concentration in the bandage after a set period of time. The validation did require altering some of our model parameters to reflect the fact that we modeled a typical wound and they tested their bandage on a bacterial biofilm, but any changes that were made were numerical and did not alter the integrity of the model. To nvestigate the effects of geometry, we also tested several slightly different bandage designs as well. Based on the information gathered from our model, we can make several recommendations about potential improvements in bandage design. First, we recommend that the vesicle wells should have a lower concentration of vesicles. This would make the bandage less expensive to produce without changing how long it takes for the bandage to fluoresce after being placed in contact with an infected wound. Decreasing the agarose concentration of the hydrogel bandage would be another potential improvement because it also would contribute to decreasing the cost of the bandage. It is important to note, however, that decreasing the percentage of agarose would also affect the mechanical properties of the bandage. This is beyond the scope of our model, but it may be an important factor to consider. A third potential improvement to the bandage would be to change the type of dye contained in the vesicles. If the current dye (6-carboxyfluorescein) was replaced with a larger dye (like sulforhodamine B), it would take longer to reach the skin after being released from the vesicles. This alteration could contribute to lowering the risk that the wound will be contaminated with dye. Another significant benefit of sulforhodamine B is that it is stable at room temperature, unlike 6-carboxyfluorescein that must be refrigerated for long-term storage. This would allow the sulforhodamine B based bandage to be more accessible in developing countries. The drawback to this dye is that it is significantly more expensive than 6-carboxyfluorescein. This expense could be offset in part by the decrease in the concentration of vesicles in the well; if there are fewer vesicles there will be less dye to pay for. Infection in burn wounds kills thousands of people every year. A bandage that informs its user when the wound is infected could drastically decrease the mortality rate, while also being a more convenient and accessible method for detecting infection.
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hydrogel bandage, diffusion, fluorescence, COMSOL, infection
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