A Reliable Murine Chronic Wound Model
Adriana C. Panayi, M.D., Ph.D., Yori Endo, M.D., Mehran Karvar, M.D., Prerana Sensharma, M.S., Valentin Haug, M.D., Siqi Fu, M.D., Bobin Mi, M.D., Yang An, M.D., Dennis P. Orgill, M.D., Ph.D..
Brigham and Women's Hospital, Boston, MA, USA.
PURPOSE: Investigators have struggled to produce a reliable chronic wound model. Recent progress with antioxidant enzyme inhibitors shows promise, but mortality rates are high. We modified the dosage and administration of an antioxidant enzyme inhibitor regimen to reduce mortality, while inducing a chronic wound environment.
METHODS: Dorsal wounds were created in 47 11-week-old db/db mice. The wound redox environment was altered in 32 mice using catalase (ATZ) and glutathione peroxidase (MSA) inhibitors. 16 mice received a collagen-glycosaminoglycan scaffold (ATZ+MSA+CGS) and 16 received a standard occlusive dressing (ATZ+MSA). 15 mice served as a db/db control (Untreated).
RESULTS: A chronic wound model was demonstrated, with no animal deaths. The model showed delayed wound contraction and poor scaffold engraftment. The ATZ+MSA treated groups had significantly higher levels of cellular infiltration, collagen deposition, keratinocytes and leucocyte infiltration than the Untreated group. Angiogenesis was significantly higher in the ATZ+MSA treated groups, but the blood vessels were shown to be immature and friable.
CONCLUSION: This study successfully induced a chronic wound in 11-week-old db/db mice. The two in vivo groups treated with the antioxidant enzyme inhibitors appeared to be arrested in the inflammatory stage, while the control group progressed to the maturation phase and ultimately remodeling. Scaffold engraftment was poor, replicating in a mouse what is seen in patients. This model may be instrumental for the development of new wound therapeutics
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