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Biofilms contribute to chronic infections and the development of antimicrobial resistance (AMR). We are developing an antimicrobial blue light (aBL) device to reduce bacterial bioburden in wounds and decrease reliance on systemic antibiotics. aBL induces the generation of reactive oxygen species (ROS) through photoexcitation of endogenous chromophores, causing bacterial damage and death. This study explores the combination of tetracyclines (TCs) with aBL for the treatment of biofilm infections in vitro. Tetracyclines (TCs), including second-generation minocycline (MC), doxycycline (DOCT), and third-generation agents omadacycline (OM) and tigecycline (TG), were evaluated for their ability to enhance bactericidal effects and ROS production during aBL treatment of abiotic biofilm. TCs were tested under dark conditions and with varying aBL light parameters against biofilms of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PA), and Escherichia coli (E. coli). Results showed that TCs alone were ineffective against these biofilm cultures. However, when combined with aBL either before or after TC treatment, significant enhancement of microbicidal activity was observed. When the aBL is added before the TCs, there was equivalent bactericidal effect, indicating that TCs primary action against biofilms were not as photosensitizers. These findings suggest that aBL can significantly enhance the antimicrobial activity of TCs, potentially offering a new effective approach to treating biofilm-associated infections and combating AMR when aBL is applicable. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

It has long been known that sensitivity to cold-induced damage can vary greatly between different cell types, with lethal temperatures reportedly ranging from −2 °C for canine osteocytes, to −70 °C for mammary adenocarcinomas. This suggests that, for certain applications, "therapeutic windows" may exist wherein the cryosurgery temperature could be controlled to specifically target more cold-sensitive cell types, while sparing less sensitive cells. However, this potential selectivity has not been developed into practical clinical treatments, in part because of a lack of available investigative tools that can provide consistent, reproducible cooling within the desired temperature range. Here we describe an experimental cryosurgery tool that allows user control over the three key cryosurgery parameters – temperature, pressure, and duration. The tool is composed of inexpensive components that are generally accessible in most laboratory settings, and could be a practical investigative tool for developing and optimizing novel topical cryosurgery approaches. [ABSTRACT FROM AUTHOR]