# Novel Approaches to Combat Medical Device-Associated BioFilms
## 3 Novel Approaches to Combat Medical Device-Associated Biofilms  
### Physical Therapy  
The removal of medical devices from the body and continuous irrigation and debridement are the most successful treatment options for eradicating biofilms when standardized antibiotic treatment fails to effectively eliminate medical device-related biofilm infections [32]. Because of technical difficulties and a high morbidity, the removal of implants infected with biofilms, such as prosthetic joints and pacemakers, may not be the best option. Photodynamic therapy (PDT) is an effective physical method for removing biofilms. It is composed of three main components: Light; a chemical molecule called a photosensitizer; and oxygen [112]. Light at a specific wavelength has an antibacterial effect. Antibacterial PDT generates highly cytotoxic reactive oxygen species (ROS) or excitable singlet oxygen to oxidize biological molecules on or within the cell membrane, such as proteins, nucleic acids, and lipids, causing cell DNA damage, cell membrane and organelle destruction, and even cell death [113] (Figure 1). A recent study has shown that PDT can not only inhibit the formation of _E. faecalis_ biofilms formed on root canals by producing ROS, but also fight against biofilm infections by inhibiting the expression of toxic factors that affect early bacterial adhesion and promote the formation of the biofilm matrix structure [114] (Figure 1). Additionally, nanomaterials (NMs) can be used in PDT to enhance the effect of PDT by generating heat or transforming NMs into biofilm-destroying species [115; 116]. PDT technology is mostly used in research on the treatment of dental plaque-related diseases [117]. PDT technology can be used to combat other implant-related biofilm infections, such as prosthetic joint infections and infections caused by ventilator-associated pneumonia biofilms [118; 119]. Although preclinical studies have suggested that PDT is a promising technique for the treatment of biofilm infections, there remain many measures that need to be taken before it can be safely applied in clinical practice. The short-term side effects of PDT are usually mild and self-limiting, such as erythema, edema, and pain in the surrounding skin, while long-term exposure to light may cause cataracts, skin cancer, and other side effects [120]. During PDT, protection measures should be taken to protect the patient's eyes from laser exposure and to ensure that the photosensitizer and photochemical reactions do not affect the patient's surrounding tissues [11]. Studies have shown that low-intensity ultrasound at the physiotherapy level can enhance the activity of antibacterial agents, resulting in a powerful biofilm removal effect [121]. Moreover, ultrasound or ultrasound-targeted microbubble destruction (UTMD) can destroy the matrix structure of bacterial biofilms by using cavitation to promote drug entry into the biofilm and can also directly destroy cells and increase the metabolic activity of cells to enhance the bactericidal ability of antibiotics [122; 123; 124] (Figure 1). These findings provide new insights for the use of ultrasound or UTMD to improve the effectiveness of antibiotic therapy for prosthesis- or catheter-related biofilms, and these approaches have shown promising effects in vivo [124; 125]. However, ultrasound-mediated antibiotic activity on bacteria in biofilms is affected by many factors, including the acoustic intensity, duty cycle, frequency, and duration [126]. For example, a greater ultrasound intensity and longer duration may cause skin or tissue damage or cause bacteria to spread to surrounding tissues and affect blood flow [127; 128]. Cavitation can also potentially damage the implant [129]. Considering that this technique may be applied to clinical practice in the future, further research is needed to select the optimal ultrasound parameters. The use of water jets is another effective physical method for removing biofilms on the surface of implants through the mechanical action of pulse and pressure [130].