Our project aims to develop a device that will aid in the treatment of wounds. We interacted with many stakeholders such as medical experts, nurses, patients, and their families, and relevant companies to make a positive impact on society. We also had the challenge of interacting with cell fiber experts to determine how yeast should be incorporated into the device during the hardware design phase. An overview of our human practice is given below.
Our interaction with Dr. Minematsu, an expert in wound care, was the cornerstone of our project design. At first, we simply targeted general wounds, but he said devices that help wounds of bedsore patients heal will have a great impact because the number of patients is increasing worldwide. He also said that since those who engage in home nursing might not be familiar with medicine, it would be useful to be able to see the healing status of wounds in color. Therefore, we decided to develop a wound dressing to assist in-home care for patients with bedsores and diabetes (see the Description section for more details).
If the bacterial flora in the wound is the same as that of healthy skin, healing is likely to proceed smoothly. Defensins are secreted in normal skin, but not in ulcers. So, he said that secreting defensins from the device is a good idea because it may bring the bacterial flora of the wound closer to that of healthy skin.
For practical use, it is important that the yeast not leak out. He also told us that interviewing Prof. Takeuchi would help us realize such a device.
We also received a lot of feedback from Dr. Minematsu. We had initially thought of focusing on oxygen levels to monitor the wound, but he suggested that other substances could be suitable for the purpose. He proposed the possibility of using cytokines. Since various cytokines are produced in bedsore wounds, monitoring several types of cytokines would help bedsore patients and their families to grasp the healing status and prognosis of the disease. This opinion inspired us to discuss whether we should incorporate cytokine monitoring into our project. One of the cytokines whose concentration changes depending on the healing state of the wound is TGF-β . We thought to detect it by expressing TGF-β receptors in yeast and transmitting the signals. However, the molecular weight of TGF-β is 25 kDa , and this molecular weight can not penetrate the cell wall . Therefore, we decided to give up monitoring wound conditions by cytokines.
We interacted with Dr. Higashimura, a specialist in geriatric nursing and an experienced home care nurse, to investigate the need for pressure ulcer treatment from a home care nurse’s perspective. In Japan, the number of patients requiring medical attention is on the rise, and the pandemic has reduced the efficiency of home nursing care, placing a heavy burden on home health nurses. The purpose of home nursing is mainly to clean patients and care for pressure ulcers, which occurs up to twice a week. The degree of pressure ulcers is assessed by the DESIGN-R evaluation standard, but judging based on it is sometimes difficult due to the lack of the family’s nursing care capability, so color monitoring of pressure ulcers by our device would be helpful.
Dr. Higashimura said the aim of home care for the bedsore depends on the family’s nursing ability. If the family has enough caregiving skills, the goal is to completely heal the bedsore, but otherwise, the aim is to maintain the current state for a long time. Therefore, we thought it would make a great impact if we were able to develop a device for home care of chronic wounds.
Dr. Higashimura also said that managing the pH of the wound may lead to healing. Keeping the pH of the bedsore low would help prevent infection. A system in which the yeast secrete substances that kept pH low could work well, but we decided to leave this as a future project because we developed a defense-secretion system for keeping wounds clean.
We interacted with geriatric nursing experts, Dr. Sanada and Dr. Nakagami, to learn more about bacterial infections. Pressure ulcers are common in the aged population, and detecting infections is significant because the geriatric population may not show an inflammatory response to pathogens due to lowered immunity. A biofilm forms within a 24-hour window, and the current treatment is physical removal. They said that devices that can detect biofilm are in demand because locating biofilm leads to effective treatment.
Dr. Sanada & Dr. Nakagami gave us a lecture on bacterial infections and biofilms, as well as some cautions on animal testing. iGEM UTokyo might conduct animal experiments at some point in the social implementation, but we should always consider whether or not we can apply the results to humans. They said there is a big gap between animal testing and human applications, so we should not overestimate the outcomes. We also have to pay attention to whether the wound model is close to the wound we want to test. Furthermore, most importantly, they also told us the ethical side, that we should decide whether to experiment or not, taking into consideration the value of the project to society, the necessity of animal testing, and animal sacrifices.
We then discussed with Prof. Takeuchi, an expert in biohybrid systems. In the interview, we confirmed that the cell confinement technology used in cell fibers is useful for our purposes, and then we discussed what specific shape of hardware is suitable to confine cells.
In the cell fiber, there is less chance of overgrowth of cells and causing necrosis, enabling long-term quality maintenance. Since our project requires dry storage and functional maintenance for about a week, we found the cell fiber to be adequate for our purpose. In addition, cell fibers allow for the exchange of signal molecules, defensins, and nutrients between the wound and the device while preventing leakage of recombinant organisms. Furthermore, cell fibers can be created at home without any specialized skills, which proved to be appropriate hardware for this project (see the Hardware section for more information).
Next, we considered if there are alternative technologies for confining cells. He said that cells could not only be confined in fiber-like materials but also in bead-like or sheet-like materials. In the end, considering our technology and the time to the competition, we decided to use fiber-like materials as hardware because of ease of handling and making.
Prof. Takeuchi also presented cautions on the use of cell fibers. He said that cell fibers could prevent cell leakage and thus protect yeast from immune cell attack, but there was a possibility of complement invasion. He also told us that yeast-derived debris could leak out of the cell fibers and cause allergies. We want to test how long the yeast would last under actual conditions of use and whether it could cause allergic reactions when the device is completed.
We interacted with those who have bedsore patients in their families to find their needs for the device, the necessity of changing its function, and their opinions on using GMOs. They said that frequent access to their house by others, such as visiting nurses, was distressing. Also, deep wounds are prone to infection and need frequent cleaning, and they are struggling with infection control. As for genetically modified organisms, as long as they are not eaten and have proper healing effects, the patient’s family are not afraid of them.
We had the opportunity to interact with the engineers of ALCARE, a company that manufactures and sells wound dressings and other medical supplies. When we told them our initial project, we received feedback that detecting infection in chronic wounds would have a stronger impact than showing healing in acute wounds. This is understandable from the dressing use of bedsore patients. In the normal use of moist bandages on shallow sores, bandages are kept stuck until the wound heals, but in the case of bedsore treatment dressings are usually changed once a day, they said. Bedsore does not heal quickly, so monitoring the healing status on a daily basis may not be so useful. Rather than that, checking infection might be helpful for prompt treatment.
Therefore, we redirected our project to target fungal infections, which are easily detected with yeast. However, literature and further interaction with ALCARE revealed that Staphylococcus aureus and Pseudomonas aeruginosa are the most common issues in bedsores, so we again changed our focus to bacterial infections (see the Description section for the design of Pathogen detection).
Wounds that may appear in good condition but are not truly healing might often have biofilms, so there was a great need to detect biofilms. Currently, a kit for detecting biofilm has been developed, but the demand for a device that works not only as a biofilm detector but also as a dressing material is expected.
The engineers of ALCARE presented possibilities for the shape of the device. They said that in deep chronic wounds, the dressing often does not fit the unevenness of the wound, so a rope-like dressing has been developed. Since the cell fiber we developed is made of alginate, a material used in actual dressings, they said that using the cell fiber directly as a dressing material would be possible. We have not yet reached the stage where we can freely adjust the strength of the cell fiber, but we would like to create such a device when we have enough technical capability.
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