Table 2.

Novel anti-biofilm therapeutic approaches. Mode of action, advantages, and disadvantages of various therapeutics are summarized

Therapeutic method	Mode of action	Advantages	Disadvantages	Ref
Sharp wound debridement	Scalpel for mechanical removal of bacterial aggregates	Improves healing outcomes, increases susceptibility to antibiotics	Temporary reduction; difficulty accessing deeper layers of infection	[49]
Hydrosurgical debridement	High-pressure waterjet for mechanical removal of bacterial aggregates	More efficient compared to sharp surgical debridement	Increased risk of air contamination	[50–52]
Ultrasound debridement	Low-frequency ultrasonic waves applied to wound; non-contact or contact application	Preserves viable granulation tissue, reduced slough and exudate	Variety of devices and settings, limited evidence for an optimal setting	[54, 55]
NPWTia	Vacuum generates sub-atmospheric pressure in wound area; topical antimicrobials delivered between cycles of negative pressure	Improves healing outcomes; enhanced effect compared to NPWT	Limited patient mobility for up to 22 h; skin irritation around wound due to device adhesion	[58, 60••, 61]
AMPsb	Molecules with antimicrobial activity that also modulate host immunity; can promote biofilm dispersal through disrupting quorum sensing and adhesion	Large database of potential natural and synthetic AMPs	Reduced peptide stability in vivo; potential cytotoxicity; potential bacterial evasion in biofilm	[74, 76]
Nanotechnology	3 mechanisms: particles that directly impair bacterial function and biofilm, carriers that deliver antimicrobials into biofilm, particles harnessing energy for physical damage	Diffusion through biofilm; can be designed for selective activation; can carry a variety of molecules	Potential cytotoxic effects depending on active molecule	[80, 85, 90]
Honey-based dressing	Bactericidal activity, inhibits bacterial adhesion to extracellular matrix components	Synergistic antibiofilm effect with adjuvant antibiotics	Antimicrobial activity varies between bacterial species	[95, 96, 100]
WEDC	Electric field generated by redox reaction across dressing, interfering with bacterial electric signaling for biofilm formation	Less risk of acquiring bacterial resistance	Lack of clinical evidence for antibiofilm efficacy	[105, 106]
Micelle matrix gel	Concentrated surfactants disrupt biofilm EPS forces and prevent biofilm formation	Noncytotoxic; less risk of acquiring bacterial resistance	Questionable efficacy against 5. aureus	[108, 109]
Xbio™ based gel	Deconstruct EPS matrix’s metallic bonds and polymers, lyses bacteria using osmolarity gradient and surfactant	Healing outcomes superior to broad-spectrum antimicrobials; reduced risk of bacterial resistance	Co-application of antibacterial therapies such as silver may interfere with technology	[108, 110, 111]
Phage therapy	Phage virus lyses targets bacterial cells and degrades biofilm matrix	Antimicrobial activity while sparing local microbiota and tissue; customized against specific bacterial strains	Narrow range of efficacy due to specificity; risk of modulating host immune system, resistance, and horizontal transfer of virulence genes	[112, 116••, 117–119]

^aNPWTi, negative pressure wound therapy with instillation

^bAMPs, antimicrobial peptides

^cWED, wireless electroceutical dressing