Abstract
Wound healing is a complex orchestration of processes involving cell proliferation, migration, differentiation, anabolism, and catabolism in order to restore skin continuity. Within these processes, elements such as metallic ions are involved due to their implications in cell behavior and enzymatic activity regulation. This study analyzed the kinetics of zinc, iron, copper and magnesium concentrations in a full thickness open wound rat model over 14 days. We made wounds with a diameter of 6 mm on the back of Lewis rats and let them heal naturally prior to analysis by histology and inductively coupled plasma mass spectrometry analysis. Histological and immunofluorescence analysis confirmed an inflammation phase until 7 days, epithelial proliferation phase from 16 h to 10 days, and remodeling phase from 7 days onward. These defined phases were correlated with the measured metal element kinetics. Zinc concentrations showed an inverted parabolic progression between 30.4 and a maximum of 39.9 μg/g dry weight. Magnesium values had a similar pattern between 283 and 499 μg/g dry weight. Copper concentrations, on the other hand, followed an inverted sigmoid trend with a decrease from 9.8 to 1.5 μg/g dry weight. Iron had a slight decrease in concentration for 24 h followed by an increase to a maximum of 466 μg/g dry weight. In conclusion, zinc, iron, and copper, even though differing in their total mass within the wound, exhibited concentration curve transitions at day 3. Interestingly, this time point correlates with the maximum proliferating keratinocyte rate during the proliferation phase.
Highlights
Open wounds create a major impact on the healthcare system because of the financial cost of the medical treatment, pain for the patient, and emotional cost from reduced self-esteem associated with scars
Despite of the use of a 6-mm diameter biopsy punch for the wounding, the embedding and microtomic processing led to an optical appearance which was larger than the the relative number of proliferative keratinocytes decreased slowly, but its level at the 14th day was still higher compared to healthy skin (163 ± 72 versus 33 ± 21 U P = 0.02)
We noticed two concentration ranges: magnesium and iron which were higher than 100 μg/g of dry weight and zinc and copper that were below 50 μg/g of dry weight
Summary
Open wounds create a major impact on the healthcare system because of the financial cost of the medical treatment, pain for the patient, and emotional cost from reduced self-esteem associated with scars. Wound healing consists of three overlapping phases, which include five processes: inflammation with hemostasis and inflammatory processes, proliferation with granulation and repidermalization processes, and the remodeling phase [1]. These phases are interdependent with each other and overlap in time. The importance of metals has been highlighted by many studies regarding metal deficiencies and the ability to reestablish wound healing by metal oral supplementation [5]. Local supplementation was shown to induce several beneficial effects including acceleration of healing and strengthening of the cicatricial tissue [6, 7]
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