Abstract
Objective: Wound healing is a complex process involving the dynamic interplay of various types of cells and bioactive factors. Impaired wound healing is characterized by a loss in synchronization of the process, resulting in non-healing chronic wounds. Human amniotic membrane (AM) has been shown to be effective in the management of chronic wounds. Recently, a viable lyopreserved AM (VLAM) has been developed. The VLAM retains the structural, molecular, and functional properties of fresh AM with the advantage of a long shelf life for living tissue at ambient temperatures. The objective of this study was to evaluate the effects of VLAM on the impaired wound microenvironment and wound closure in db/db mice.Approach: VLAM or saline gel (control) was applied weekly to 7-mm excisional wounds in diabetic (db/db) mice. Wound appearance and size were assessed weekly. Inflammation and redox state in wounds were tested by cytokine gene and protein expression, and by catalase and glutathione peroxidase activities, respectively. Wound tissue granulation and neovascularization were assessed histologically.Results: Diabetic wounds treated with VLAM closed faster than control wounds. On an average, VLAM-treated wounds closed 4 days faster than the control wounds, with a significantly faster rate of closure at days 7 and 14 as compared with control wounds. The faster closure correlated with a decrease in the expression of proinflammatory factors and oxidative stress, and an increase in angiogenesis and dermal thickness.Innovation: Effects of VLAM on a chronic wound microenvironment and underlying molecular mechanisms were investigated for the first time.Conclusion: VLAM accelerates wound closure in db/db mice by decreasing inflammation and oxidative stress and supporting wound tissue granulation, neovascularization, and re-epithelialization.
Highlights
Normal wound healing is a physiological response to tissue injury
We used this model to investigate the rate of wound closure in viable lyopreserved AM (VLAM)-treated animals and compared these data with those in control and Devitalized lyopreserved AM (DLAM)-treated animals
To determine the effect of VLAM treatment on oxidative stress in diabetic mouse wounds, we examined the activity of antioxidant enzymes catalase and glutathione peroxidase in wound samples collected on day 7
Summary
Normal wound healing is a physiological response to tissue injury. Wound healing is a dynamic, complex process with four overlapping phases: homeostatic, inflammatory, proliferative, and remodeling.[1] Each phase of wound healing involves coordinated activities of numerous types of cells and bioactive factors. Obesity, smoking, and many diseases, including diabetes, cardiovascular and kidney diseases, have negative effects on wound healing. Impaired wound healing is characterized by a loss in synchronization of the process, resulting in chronic non-healing wounds. Hallmarks of chronic wounds include inflammation, exacerbated levels of proteases and reactive oxygen species (ROS), and biofilm-forming bacteria.[1,2,3,4] The number of people with chronic wounds is rapidly growing, reaching almost 7 million with an approximate annual cost of $25B in the United States alone.[3] Despite having a broad variety of advanced wound therapies available, chronic wounds remain a treatment challenge
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