# Novel Approaches to Combat Medical Device-Associated BioFilms
## 3 Novel Approaches to Combat Medical Device-Associated Biofilms
### Antimicrobial Peptides
Temporin 1 Tb, derived from frog skin, can also kill both developing and mature _S. epidermidis_ biofilms [191]. Some AMPs can impair EPS production to cause structural changes and degradation of the biofilm matrix. The synthetic peptide P1, derived from a tick antifreeze protein, significantly reduced _S. mutans_ biofilm formation in an in vitro microplate assay and in a saliva-coated hydroxyapatite disc tooth model through the degradation of EPS and destruction of the biofilm structure [192]. TL can also affect mature biofilms in _Pseudomonas fluorescens_, and a large portion of the preformed biofilm architecture was clearly perturbed by addition of the peptide, with a significant decrease in all biofilm surface parameters and the overall biomass [181]. Hepcidin 20, which is an antimicrobial peptide derived from the human liver, can reduce the mass of the extracellular matrix and change the structure of biofilms of _S. epidermidis_ by targeting the intracellular polysaccharide adhesion [193]. The fish-derived AMP piscidin-3 has nucleosidase activity and can destroy the extracellular DNA of _P. aeruginosa_ through its N-terminal coordination with Cu\({}^{2+}\)[194]. (LIN-SB056-1)\({}_{2}\)-K was also proven to disrupt the _P. aeruginosa_ biofilm structure in an ex vivo model [195]. Some AMPs, as immune modulators, recruit immune cells at the site of infection, enhance the activity of host immune cells, and regulate the inflammatory response [196]. Some AMPs can resist endotoxin activity and neutralize proinflammatory factors, which may cause serious complications and damage to the body [197]. Some AMPs also display a synergistic effect when combined with traditional antibiotics via the promotion of antibiotic uptake [198]. We have listed the representative AMPs and their antibiofilm effects and mechanisms of action in Table 3.  
Some AMPs have been applied to multi-drug resistance in clinical practice, such as colistin and polymycin B. The modes of their application include intravenous or topical administration (such as intrathecal injection and atomization inhalation) [199]. International consensus guidelines have recommended intravenous doses of colistin and polymycin B based on the kidney function of patients [200]. Some AMPs are prepared as ointments for infections of superficial tissues or medical device surfaces [190]. Most of the new AMPs have not been applied to humans and the experiments have been carried out in vitro or in animal experiments. However, many studies have provided inspiring results and the in vivo data have provided valuable references for the therapeutic dose, safety, and stability of AMPs for further clinical practice in humans. For example, in an animal experiment, 50 mg/kg administration of the four cathelicidins (Cathelicidin-BF, Pc-CATH1, Cc-CATH2, Cc-CATH3) could significantly reduce the fungal counts in a murine oral candidiasis model induced by clinically isolated _C. albicans_ with slight hemolytic activity. Cathelicidin-BF strongly inhibited _C. albicans_ biofilm formation at 20 \(\upmu\)g/mL [171]. In an in vitro experiment simulating real flow conditions in the human body, Temporin-L(TL) had an anti-biofilm effect without increasing cell damage, demonstrating that it has great potential for clinical application [181]. The anti-biofilm doses of AMPs in the above experiments are shown in Table 3.  
\begin{table}
\begin{tabular}{c c c c c c c} \hline
**AMP** & **Fathogen** & **Infection Model** & **MIC** & **MBIC/EC** & **Effects and Mechanism of Action** & **Reference** \\ \hline IC-31 & _S. mutans_ & in vitro & 5 \(\mu\)M & 6.92 \(\mu\)M & Disrupt the bacterial membrane, causing leakage of the contents; regulate the inflammatory response & [167] \\ IC-35-2 (M) & _S. mutans_ & in vitro & 5 \(\mu\)M & 7.58 \(\mu\)M & The membrane and kill bacteria by regulating physiological metabolic processes, including protein synthesis, peptide glycan & [172] \\ B22 (M) & _P. aeruginosa_ & in vitro