Low mortality oxidative stress murine chronic wound model

Abstract

IntroductionInvestigators 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.Research design and methodsTo chemically induce a chronic wound environment, we applied modified doses of catalase (3-amino-1,2,4-triazole; intraperitoneal 0.5 g/kg) and glutathione peroxidase (mercaptosuccinic acid; topical 300 mg/kg) inhibitors to the dorsal wounds of 11-week-old db/db mice. A cohort of these mice was treated with a collagen-glycosaminoglycan scaffold. Both groups were compared with Diabetic control mice.ResultsThis study successfully induced a chronic wound in 11-week-old db/db mice, with no animal deaths. The antioxidant enzyme treated groups showed delayed wound contraction and significantly higher levels of inflammatory tissue, collagen deposition, cellular proliferation and leukocyte infiltration than the Diabetic control group. Angiogenesis was significantly higher in the antioxidant enzyme treated groups, but the vessels were immature and friable. Scaffold engraftment was poor but appeared to promote blood vessel maturation.ConclusionsOverall, the two in vivo groups treated with the antioxidant enzyme inhibitors appeared to be arrested in the inflammatory stage of wound healing, while the Diabetic control group progressed to the maturation phase and ultimately remodeling. This model may be instrumental for the development of new wound therapeutics.

Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis

“…Accumulating evidence has supported that enhanced angiogenesis can improve the delivery of nutrients and oxygen to the wound sites, which can accelerate wound healing [ 10 , 11 ]. An effective strategy that promotes wound angiogenesis can accelerate wound healing and has the potential to revolutionize the treatment of patients with diabetes [ 12 , 13 ].…”

The Three-Dimensional Structure of Porcine Bladder Scaffolds Alters the Biology of Murine Diabetic Wound Healing

“…Anti-CD31-probed slides were used to calculate the microvessel density, and combined assessment of anti-CD31 and anti-SMA was used to establish the maturity of new blood vessels through the microvascular pericyte coverage index. 18,19…”

“…The investigators performed quantitative analyses using samples of the wound bed and borders on day 10 postsurgery, as previously described. 18,19 The hematoxylin and eosin-and Masson trichrome-stained sections were used to assess wound bed thickness and collagen deposition, respectively. Anti-CD45-, anti-Ki-67, and anti-K17-probed sections were used to assess leukocyte infiltration, cell proliferation, and keratinocyte migration, respectively.…”

“…In a recent study, modification of the redox environment in db/db mice led to the development of chronic wounds. 19 To expand on the current work, future research could use a chronic wound model to assess the different scaffold combinations.…”

Antioxidant Therapy and Antioxidant-Related Bionanomaterials in Diabetic Wound Healing

“…Antioxidant enzymes play a crucial role in oxidative stress and chronic diabetic wounds ( Panayi et al, 2020 ). Major antioxidant enzymes include superoxide dismutase (SOD), catalase, glutathione peroxidase, and heme oxygenase.…”