Abstract
Bacterial biofilms are often found in chronically infected wounds. Biofilms protect bacteria from antibiotics and impair wound healing. Surgical debridement is often needed to remove the biofilm from an infected wound. Laser-generated shockwave (LGS) treatment is a novel tissue-sparing treatment for biofilm disruption. Previous studies have demonstrated that LGS is effective in disrupting biofilms in vitro. In this study, we aim to determine the safety threshold of the LGS technology in an in vivo rodent model. To understand the in vivo effects of LGS on healthy cutaneous tissue, the de-haired dorsal skin of Sprague-Dawley rats were treated with LGS at three different peak pressures (118, 296, 227 MPa). These pressures were generated using a 1064 nm Nd/YAG laser (pulse duration 5 ns and laser fluence of 777.9 mJ) with laser spot size diameters of 2.2, 3.0, and 4.2 mm, respectively. Following treatment, the animals were observed for 72 h, and a small subset was euthanized at 1-h, 24-h, and 72-h post-treatment and assessed for tissue injury or inflammation under histology. Each treatment group consisted of 9 rats (n = 3/time point for 1-h, 24-h, 72-h post-treatment). An additional 4 control (untreated) rats were included in the analysis, for a total of 31 animals. Gross injuries occurred in 21 (77%) animals and consisted of minor erythema, with prevalence positively correlated with peak pressure (p < 0.05). Of injuries under gross observation, 94% resolved within 24 h. Under histological analysis, the injuries and tissue inflammation were found to be localized to the epidermis and superficial dermis. LGS appears to be well tolerated by cutaneous tissue for the laser energy settings shown to be effective against bacterial biofilm in vitro. All injuries incurred, at even the highest peak pressures, were clinically mild and resolved within 1 day. This lends further support to the overall safety of LGS and serves to translate LGS towards in vivo efficacy studies.
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References
Cosgrove SE (2006) The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis 42(Suppl 2):S82–S89
Sheng W-H, Chie W-C, Chen Y-C, Hung C-C, Wang J-T, Chang S-C (2005) Impact of nosocomial infections on medical costs, hospital stay, and outcome in hospitalized patients. J\ Formos Med Assoc 104:318–326
Merritt JH, Kadouri DE, O'Toole GA (2014) Wound care market by type (traditional (wound closure, anti infective), basic (films, cleansing), advanced (hydrogels, hydrocolloids, alginate, collagen), active (artificial skin & skin substitutes), pressure relief devices, NPWT). Markets and Markets
Markets for advanced wound management technologies (2014) Wellesley, MA
Fonder MA, Lazarus GS, Cowan DA, Aronson-Cook B, Kohli AR, Mamelak AJ (2008) Treating the chronic wound: a practical approach to the care of nonhealing wounds and wound care dressings. J Am Acad Dermatol 58(2):185–206
Costerton JW, Cheng KJ, Geesey GG, Ladd TI, Nickel JC, Dasgupta M, Marrie TJ (1987) Bacterial biofilms in nature and disease. Annu Rev Microbiol 41:435–464
Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM (1995) Microbial biofilms. Annu Rev Microbiol 49(1):711–745
Costerton JW, Lewandowski Z, DeBeer D, Caldwell D, Korber D, James G (1994) Biofilms, the customized microniche. J Bacteriol 176(8):2137
Jones ME, Karlowsky JA, Draghi DC, Thornsberry C, Sahm DF, Nathwani D (2003) Epidemiology and antibiotic susceptibility of bacteria causing skin and soft tissue infections in the USA and Europe: a guide to appropriate antimicrobial therapy. Int J Antimicrob Agents 22:406–419
Jones RN (2001) Resistance patterns among nosocomial pathogens: trends over the past few years. Chest 119:397S–404S
Livermore DM (2007) Introduction: the challenge of multiresistance. Int J Antimicrob Agents 29(Suppl 3):S1–S7
Bjarnsholt T (2013) The role of bacterial biofilms in chronic infections. APMIS Suppl (136):1–51. https://doi.org/10.1111/apm.12099
Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, Scheld WM, Bartlett JG, Edwards J, of America IDS (2008) The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis 46:155–164
James GA, Swogger E, Wolcott R, Pulcini E, Secor P, Sestrich J, Costerton JW, Stewart PS (2008) Biofilms in chronic wounds. Wound Repair Regen 16:37–44
Bowler PG (2002) Wound pathophysiology, infection and therapeutic options. Ann Med 34:419–427
Halim AS, Khoo TL, Saad AZM (2012) Wound bed preparation from a clinical perspective. Indian J Plastic Surg 45:193–202
Francis NC, Kassam I, Nowroozi B, Grundfest WS, Taylor ZD (2015) Analysis of flexible substrates for clinical translation of laser-generated shockwave therapy. Biomed Opt Express 6(3):827–837
Navarro A, Taylor ZD, Matolek AZ, Weltman A, Ramaprasad V, Huang S, Beenhouwer DO, Haake DA, Gupta V, Grundfest WS (2010) Bacterial biofilm disruption using laser-generated shockwaves. In: Infect Drug Resist. pp 82141H-82141H-82148
Ramaprasad V, Navarro A, Patel S, Patel V, Nowroozi BN, Taylor ZD, Yong W, Gupta V, Grundfest WS (2014) Effect of laser generated shockwaves 1 on ex-vivo pigskin. Lasers Surg Med 46:620–627
Taylor ZD, Navarro A, Kealey CP, Beenhouwer D, Haake DA, Grundfest WS, Gupta V (2010) Bacterial biofilm disruption using laser generated shockwaves. In: Engineering in Medicine and Biology Society (EMBC), 2010 Annual International Conference of the IEEE. pp 1028-1032
Yao W, Kuan EC, Francis NC, St John MA, Grundfest WS, Taylor ZD (2017) Laser-generated shockwaves enhance antibacterial activity against biofilms in vitro. Lasers Surg Med 49:539–547
Francis NC, Yao W, Grundfest WS, Taylor ZD (2017) Laser-generated shockwaves as a treatment to reduce bacterial load and disrupt biofilm. IEEE Trans Biomed Eng 64(4):882–889
Nigri GR, Tsai S, Kossodo S, Waterman P, Fungaloi P, Hooper DC, Doukas AG, LaMuraglia GM (2001) Laser-induced shock waves enhance sterilization of infected vascular prosthetic grafts. Lasers Surg Med 29(5):448–454
Krespi YP, Stoodley P, Hall-Stoodley L (2008) Laser disruption of biofilm. Laryngoscope 118(7):1168–1173
Fife CE, Carter MJ (2012) Wound care outcomes and associated cost among patients treated in US outpatient wound centers: Data From the US Wound Registry. Wounds 24:10–17
Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT (2009) Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen 17:763–771
Yao W, Kuan EC, Chung YH, Francis NC, St John MA, Taylor ZD, Grundfest WS (2019) In-depth analysis of antibacterial mechanisms of laser generated shockwave treatment. Lasers Surg Med 51(4):339–344. https://doi.org/10.1002/lsm.23018
Lee S, Kollias N, McAuliffe DJ, Flotte TJ, Doukas AG (1999) Topical drug delivery in humans with a single photomechanical wave. Pharm Res 16:1717–1721
Matlaga BR, McAteer JA, Connors BA, Handa RK, Evan AP, Williams JC, Lingeman JE, Willis LR (2008) Potential for cavitation-mediated tissue damage in shockwave lithotripsy. J Endourol 22(1):121–126
Evan AP, Willis LR, Lingeman JE, McAteer JA (1998) Renal trauma and the risk of long-term complications in shock wave lithotripsy. Nephron 78(1):1–8
Acknowledgment
The authors would like to thank Michael C. Fishbein, MD, for his guidance and assistance in the analysis of the histological data.
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This research was generously supported by the American Society for Laser Medicine & Surgery (ASLMS) student research grant and ASLMS travel grant.
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This study was performed with the approval of University of California Los Angeles Institutional Animal Care and Use Committee (protocol #2013-018-01).
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Yao, W., Kuan, E.C., Grundfest, W.S. et al. Safety of laser-generated shockwave treatment for bacterial biofilms in a cutaneous rodent model. Lasers Med Sci 36, 1403–1410 (2021). https://doi.org/10.1007/s10103-020-03171-3
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DOI: https://doi.org/10.1007/s10103-020-03171-3