Abstract
A rapid wound healing is beneficial for not only recovering esthetics but also reducing pain, complications and healthcare burdens. For such a purpose, continuous efforts have been taken to develop viable dressing material. Acellular dermal matrix (ADM) paste has been used to repair burn wounds and is shown to promote angiogenesis as well as fibroblast attachment and migration. However, its efficacy still needs to be significantly improved to meet clinical demands for accelerating acute skin wound healing. To approach this problem, we studied the added value of a human salivary peptide — Histatin 1 (Hst1). Hst1 was chosen because of its potency to promote the adhesion, spreading, migration, metabolic activity and cell-cell junction of major skin cells and endothelial cells. In this study, we hypothesized that ADM paste and Hst1 showed a better effect on the healing of surgically created acute skin wounds in mice since ADM paste may act as a slow release system for Hst1. Our results showed that the healing efficacy of 10 μM topically administrated Hst1 was significantly higher compared to the control (no Hst1, no ADM) from day 3 to day 10 post-surgery. In contrast, ADM alone failed in our system at all time points. Also, the combination of ADM paste and Hst1 did not show a better effect on percentage of wound healing. Histological analysis showed that 10 μM Hst1 was associated with maximal thickness of newly formed epidermal layer on day 7 as well as the largest collagen area on day 14. In addition, immunohistochemical staining showed that the number of CD31-positive blood vessels in the group of 10 μM Hst1 was 2.3 times compared to the control. The vascular endothelial growth factor (VEGF) expression in the groups of 10 μM Hst1 group and ADM + 10 μM Hst1 group was significantly higher compared with the control group. Furthermore, 10 μM Hst1 group was associated with significantly lower levels of CD68-positive macrophage number, interleukin-1β (IL-1β) expression and C-reactive protein (CRP) expression than those of the other groups (control, ADM alone and ADM + 10 μM Hst1). In contrast, ADM was only associated with significantly lower CD68-positive macrophage number and IL-1β expression in comparison with the control. The co-administration of Hst1 and ADM paste did not yield more beneficial effects than Hst1 alone. In conclusion, the topically administrated of 10 μM Hst1 could be a promising alternative dressing in managing acute wound healing.
Highlights
Acute skin wounds may be caused by trauma, burns, lacerations or abrasions and surgery
We adopted Histatin 1 (Hst1) at its optimal concentration (10 μM) and corresponding groups, such as control (no ADM, no FIGURE 1 | 3, 5, 7, and 10 days post-surgery, the dynamic changes of wound area in different groups after treatment. (A) Representative images of acute wounds showed that the wound area treated by 10 μM Hst1 was significantly smaller than the other groups; (B) The temporal changes of wound healing percentage (%) in each treatment group
On days 3, 5, and 10, the healing percentage of the wounds treated by 10 μM Hst1 was significantly higher than the control; (C) ADM + 10 μM Hst1 was associated with significantly higher healing percentage than the ADM and the control on days 3 and 5
Summary
Acute skin wounds may be caused by trauma, burns, lacerations or abrasions and surgery. At 48 and 72 h after injury, M1 macrophages transit to M2 macrophages and secrete a series of growth factors including TGF-β1 (transfer growth factor-β1) and VEGF-α (vascular endothelial growth factor-α), which promote angiogenesis and re-epithelialization (Vannella and Wynn, 2017; Klar et al, 2018). These growth factors stimulate the synthesis and secretion of large amounts of collagen fibers and matrix components by fibroblasts to form connective tissues (Liebl and Kloth, 2012). Continuous attempts have been made to develop suitable wound dressings to accelerate wound healing by targeting and stimulating the abovementioned biological events
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