R. E. Jones1,2, A. L. Moore2,3, M. P. Murphy2, D. S. Foster2, S. Mascharak2, B. Duoto2,4, D. Irizarry2,5, E. A. Brett2, G. Wernig6, M. T. Longaker2 1University Of Texas Southwestern Medical Center,General Surgery,Dallas, TX, USA 2Stanford University,Department Of Surgery,Palo Alto, CA, USA 3Brigham And Women’s Hospital,Department Of Surgery,Boston, MA, USA 4San Jose State University,San Jose, CA, USA 5Beth Israel Deaconess Medical Center,Department Of Surgery,Boston, MA, USA 6Stanford University,Department Of Pathology,Palo Alto, CA, USA
Introduction: Cutaneous scarring represents a challenging clinical problem which results in disability, deformity, and psychosocial dysfunction. Matrix metalloproteinase inhibitors are important in regulating scar tissue deposition and extracellular matrix remodeling. Doxycycline is an antibiotic approved by the Federal Drug Administration known to function as a matrix metalloproteinase inhibitor. Given this chemical quality, we theorized that doxycycline may positively affect wound healing. We tested the effect of locally-applied doxycycline on skin fibrosis and bacterial contamination.
Methods: Experiments were conducted with C57BL/J6 mice to test scar thickness, tensile strength, and bacterial colony load in wounds treated with doxycycline or phosphate buffered sodium (PBS). All mice underwent dorsal excisional skin wounding in accordance with previously published work. Doxycycline or PBS was then injected into the base of acute wounds at varying concentrations. Wounds were harvested 15 days postoperatively. Histologic analyses were performed to measure scar thickness and collagen content, including staining with hematoxylin and eosin, trichrome, and picrosirius red. The tensile strength of healed wounds was tested. Wounds were swabbed and cultured, and bacterial colonies were tabulated. Results were compared utilizing the Mann-Whitney U test.
Results: Scar thickness was significantly decreased by 37% in wounds treated with 2 mg/mL doxycycline versus PBS (*p = 0.0107). Doxycycline treated wounds exhibited significantly decreased proportions of mature collagen as compared to control wounds (*p = 0.0470). Bacterial loads were similar at postoperative days 1, 3, 5, 7 and 9 in doxycycline and control mice (p > 0.05). Finally, tensile strength was not significantly different in treatment versus control mice (p = 0.6334).
Conclusions: We show that local application of 2 mg/mL doxycycline decreases scarring in comparison to PBS treated wounds without compromising tensile strength. Additionally, bacterial contamination in treated versus control wounds was not significantly different, suggesting that doxycycline functions as a vulnerary agent to reduce fibrosis in non-antimicrobial manner. Given the longstanding safety profile of doxycycline, this application could be rapidly translated for use in acute injury, postoperatively, hypertrophic scars and keloids, and burns.
