Doxycycline Reduces Scar Thickness and Improves Collagen Architecture

Abstract

Objective: To investigate the effects of local doxycycline administration on skin scarring. Background: Skin scarring represents a major source of morbidity for surgical patients. Doxycycline, a tetracycline antibiotic with off-target effects on the extracellular matrix, has demonstrated antifibrotic effects in multiple organs. However, doxycycline's potential effects on skin scarring have not been explored in vivo. Methods: Female C57BL/6J mice underwent dorsal wounding following an established splinted excisional skin wounding model. Doxycycline was administered by local injection into the wound base following injury. Wounds were harvested upon complete wound closure (postoperative day 15) for histological examination and biomechanical testing of scar tissue. Results: A one-time dose of 3.90mM doxycycline (2mg/mL) within 12 hours of injury was found to significantly reduce scar thickness by 24.8% (*P < 0.0001) without compromising tensile strength. The same effect could not be achieved by oral dosing. In doxycycline-treated scar matrices, collagen I content was significantly reduced (*P = 0.0317) and fibers were favorably arranged with significantly increased fiber randomness (*P = 0.0115). Common culprits of altered wound healing mechanics, including angiogenesis and inflammation, were not impacted by

Mechanical stretch promotes hypertrophic scar formation through mechanically activated cation channel Piezo1

“…The decreased biomechanical function of scars highlights the need for clinical therapies to improve the scar tensile strength 66 . It is reported that very few effective therapies exist which inhibit scar formation while maintaining scar tensile strength 67 . Ward et al revealed that subcutaneous injection of GsMTx4 improved muscle strength of mice 68 .…”

Angiogenesis in Chronic Inflammatory Skin Disorders

“…Doxycycline is a broad-spectrum tetracycline-class antibiotic that inhibits the 30S ribosome subunit; the drug also has an anti-inflammatory effect [ 53 ]. Several reports on the effects of doxycycline on the ocular system [ 93 ], the oral cavity, intracranial venous hypertension [ 94 ], skin scarring [ 49 ], and rosacea have appeared. In patients with intracranial venous hypertension, doxycycline inhibits angiogenesis by reducing microvessel density, suppressing MMP-3 overexpression, and reducing VEGF and TGF-β levels [ 94 ].…”

The Spectrum of Scarring in Craniofacial Wound Repair

“…For example, Qi et al reported that hydrogels made from sericin (a silk-derived natural biomaterial) resulted in accelerated healing with reduced inflammation and features of regeneration (e.g., increased hair follicle neogenesis) in a preclinical mouse model (Qi et al, 2018). Identification of novel anti-scarring drugs is also an active area of research; for instance, a study from our laboratory recently established doxycycline as a putative anti-scarring agent which reduces fibrosis and promotes features of regeneration in a splinted mouse wound healing model (Moore et al, 2018). Translation of these discoveries into a clinical setting, and continued exploration of scarring from the lenses described in this article, will lead to continued advancement in our ability to treat and improve craniofacial wound healing.…”