Laser Generated Shockwave Therapy of Bacterial Biofilms: From Benchtop to Pre-Clinical Studies

The presence of bacterial biofilms in wounds presents a major complication in wound treatments, significantly increasing morbidity and mortality. Biofilms delay wound healing, promote the growth of bacteria, and are a persistent source of pathogens that can infect other wounds. They are natively resistant to surfactants, antibiotics, and antiseptics, causing many current anti-bacterial treatments to remain ineffective at improving patient outcomes. Alternative methods for wound management often remove healthy tissue, along with the biofilm, resulting in unacceptable injuries to the patient. This work investigated a novel method of mechanically disrupting and removing persistent biofilms with laser generated shockwaves (LGS). We have demonstrated that LGS therapy can eliminate bacterial biofilms without damaging the surrounding tissue. This study further developed practical and effective methods of delivering LGS in patients. We have developed a portable raster scanner, capable of delivering LGS at a rate of 5 shockwaves per second, with peak pressures of >200 MPa, computer-aided targeting, and a treatment area of 4 x 6 cm2. Using this system, we have demonstrated that LGS can remove 99.4% of biofilm matrix and 97.7% of surface CFUs.This study also investigated the ability of LGS therapy to facilitate antibiotic delivery through biofilms. We have shown that LGS can increase the effectiveness of gentamicin by 21.4%, when used against Staphylococcus epidermidis biofilm grown in vitro, indicating that LGS can help restore the effectiveness of treatments that were hindered by the presence of biofilms. When used against S. epidermidis biofilm grown on ex vivo tissue, LGS can still remove 69% of CFUs and cause a 52% reduction in biofilm coverage, without damage to the underlying tissue.In bringing this technology forward, we have demonstrated that LGS is safe and well-tolerated when used on intact skin in rodents. When used at the maximal therapeutic window of 295.6 � 35.4 MPa, no hemorrhages nor damage to the dermis were seen after treatment. The only damage observed were minor injuries to the epidermis that resolve within three days. Preliminary followup results in rodents showed that these minor injuries cause no statistical differences in healing times between LGS-treated excisional wounds and controls