scholarly journals Eden Model Simulation of Re-Epithelialization and Angiogenesis of an Epidermal Wound

Processes ◽  
2018 ◽  
Vol 6 (11) ◽  
pp. 207
Author(s):  
Ephraim Agyingi ◽  
Luke Wakabayashi ◽  
Tamas Wiandt ◽  
Sophia Maggelakis

Among the vital processes of cutaneous wound healing are epithelialization and angiogenesis. The former leads to the successful closure of the wound while the latter ensures that nutrients are delivered to the wound region during and after healing is completed. These processes are regulated by various cytokines and growth factors that subtend their proliferation and migration into the wound region until full healing is attained. Wound epithelialization can be enhanced by the administration of epidermal stem cells (ESC) or impaired by the presence of an infection. This paper uses the Eden model of a growing cluster to independently simulate the processes of epithelialization and angiogenesis in a cutaneous wound for different geometries. Further, simulations illustrating bacterial infection are provided. Our simulation results demonstrate contraction and closure for any wound geometry due to a collective migration of epidermal cells from the wound edge in fractal form and the diffusion of capillary sprouts with the laying down of capillary blocks behind moving tips into the wound area.

2021 ◽  
Author(s):  
Si-Min Zhang ◽  
Chuan-Yuan Wei ◽  
Qiang Wang ◽  
Lu Wang ◽  
Lu Lu ◽  
...  

Abstract Background: Timely and sufficient recruitment of M1 macrophages and M2 polarization are necessary for fibrous repair during cutaneous wound healing. The inherent mechanism of how M2 polarization mediate wound healing is worth exploring and illustrating. Abnormally up-regulated connective tissue growth factor (CTGF) is closely related with multiple organ fibrosis, including cardiac, pulmonary, hepatic, renal, and cutaneous fibrosis. Previous studies have reported that M2-polarized macrophages contribute to hepatic and renal fibrosis by secreting CTGF. It is worth discussing if M2 macrophages regulate fibrosis through secreting CTGF in cutaneous wound healing.Methods: We established the murine full-thickness excisional wound model and inhibited macrophages during proliferation phase (mainly M2 and M1-M2 polarization) with clodronate liposomes to analyze how M2 macrophages mediate wound healing rates, collagen deposition, collagen 1/3 expression, and Ki67 expression in vivo. Furthermore, M2 polarization was induced by IL-4 and in vitro. F4/80+CD206+ M2 macrophages were measured by flow cytometry. The morphological characteristics were observed. Secretion of IL-6, TNF-α, IL-10, TGF-β1, and CTGF was tested by ELISA. CTGF gene of M2 was blocked using siCTGF. Effects of M2 on proliferation and migration of fibroblasts were detected by CCK8 and cellular wound healing assay. Protein level of AKT, ERK1/2, and STAT3 pathway were assessed by western blotting.Results: Depletion of macrophages at proliferation phase (mainly M2 and M1-M2 polarization) resulted in delayed cutaneous wound closure and down-regulation of wound healing rates, collagen deposition, collagen 1/3 expression, and Ki67 expression. M2 polarization was induced, which producing more CTGF, TGF-β1, and IL-6, as well as less TNF-α and IL-10. Blockade of CTGF in M2 macrophages deactivated fibroblast proliferation and migration. Addition of recombinant CTGF restored the promotional effects of M2 macrophages on fibroblast proliferation and migration. Blockade of CTGF in M2 mediate fibroblasts via down-regulating AKT, ERK1/2, and STAT3 signaling pathway.Conclusion: Our research, for the first time, indicated that M2-polarized macrophages promoted cutaneous wound healing by secreting CTGF, which further mediating proliferation and migration of fibroblasts via AKT, ERK1/2, and STAT3 signaling pathway.


Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1595 ◽  
Author(s):  
Sungjoo Park ◽  
Eunsu Ko ◽  
Jun Hyoung Lee ◽  
Yoseb Song ◽  
Chang-Hao Cui ◽  
...  

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Kanae Mukai ◽  
Yukari Nakajima ◽  
Tamae Urai ◽  
Emi Komatsu ◽  
Kana Takata ◽  
...  

Estrogen replacement promotes cutaneous wound healing in 8–10-week young ovariectomized female mice. However, research using aged ovariectomized female mice has not been reported, to the best of our knowledge. Therefore, we investigated the effect of 17β-estradiol on cutaneous wound healing using 24-week middle-aged ovariectomized female mice. Twenty-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX), and sham (SHAM). After 4 weeks, the mice received two full-thickness wounds. Then, the OVX + 17β-estradiol group was administered 17β-estradiol at 0.01 g/day until healing. The ratio of wound area in the OVX + 17β-estradiol group was significantly decreased compared with that in the OVX group. The numbers of neutrophils and macrophages in the OVX + 17β-estradiol group were significantly smaller than those in the OVX group. In addition, the ratio of myofibroblasts in the OVX + 17β-estradiol group was significantly higher than that in the OVX group. These data suggested that exogenous continuous 17β-estradiol administration promotes cutaneous wound healing in 24-week OVX female mice by reducing wound area, shortening inflammatory response, and promoting wound contraction. However, it is unclear whether the effect of exogenous estrogen on wound healing outweighs the delay of wound healing due to advanced age.


2008 ◽  
Vol 34 (2) ◽  
pp. 162-184 ◽  
Author(s):  
Sashwati Roy ◽  
Savita Khanna ◽  
Cameron Rink ◽  
Sabyasachi Biswas ◽  
Chandan K. Sen

This work represents a maiden effort to systematically screen the transcriptome of the healing wound-edge tissue temporally using high-density GeneChips. Changes during the acute inflammatory phase of murine excisional wounds were characterized histologically. Sets of genes that significantly changed in expression during healing could be segregated into the following five sets: up-early (6–24 h; cytokine-cytokine receptor interaction pathway), up-intermediary (12–96 h; leukocyte-endothelial interaction pathway), up-late (48–96 h; cell-cycle pathway), down-early (6–12 h; purine metabolism) and down-intermediary (12–96 h; oxidative phosphorylation pathway). Results from microarray and real-time PCR analyses were consistent. Results listing all genes that were significantly changed at any specific time point were further mined for cell-type (neutrophils, macrophages, endothelial, fibroblasts, and pluripotent stem cells) specificity. Candidate genes were also clustered on the basis of their functional annotation, linking them to inflammation, angiogenesis, reactive oxygen species (ROS), or extracellular matrix (ECM) categories. Rapid induction of genes encoding NADPH oxidase subunits and downregulation of catalase in response to wounding is consistent with the fact that low levels of endogenous H2O2is required for wound healing. Angiogenic genes, previously not connected to cutaneous wound healing, that were induced in the healing wound-edge included adiponectin, epiregulin, angiomotin, Nogo, and VEGF-B. This study provides a digested database that may serve as a valuable reference tool to develop novel hypotheses aiming to elucidate the biology of cutaneous wound healing comprehensively.


Author(s):  
Martha Orendu Attah ◽  
Tonye Watson Jacks ◽  
Attah Jacob ◽  
Otong Eduitem ◽  
Barnabas John

Background: In the present research study, the rate of cutaneous wound healing and contraction rate in healthy rabbits using Aloe vera pulp was studied.Methods: Ten healthy rabbits were used for the study. They were divided into two groups consisting of five rabbits each. Cutaneous wounds were made on the lumbar region of each rabbit using a template which ensured that the wounds were of the same size in all the rabbits. 5ml of Aloe vera gel was applied to the wounds of the animals in the test group, while nothing was applied to the wound area of the animals in the control group. The wound area in each group was measured for a period of 21 days, using a venire caliper and tracing paper which was used to trace the wound area. Tissue samples were removed from the wound area in both experimental and control groups and subjected to routine histological analysis, also, morphometric analysis was performed.Results: The rate of wound contraction and mean centripetal contraction was calculated in both groups and graphically represented using Microsoft Excel. The results showed that animals who were treated with Aloe vera gel had a greater wound contraction rate, as well as rapid wound closure. The micrographs showed a thicker epithelial layer, with thinner collagen fibers in the dermis of experimental animals compared to the control group. There was also an abundant capillary bed at the dermal-epidermal junction in the experimental group, compared to the control group.Conclusion:  Aloe vera may increase the rate of wound healing by accelerating epithelial migration, and may also play a role in neo-vascularization of the newly healed area.Keywords: Aloe vera, Cutaneous Wounds, Rabbits, Wound Contraction, Wound Healing


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Kanae Mukai ◽  
Miki Koike ◽  
Saki Nakamura ◽  
Yuka Kawaguchi ◽  
Fumika Katagiri ◽  
...  

The aim of this study was to evaluate the effect of the combined use of Japanese honey and hydrocolloid dressing (HCD) on cutaneous wound healing. Mice were divided into four groups: the Acacia (Japan) + HCD, Manuka (New Zealand) + HCD, Chinese milk vetch (Japan) + HCD, and HCD (control) groups. The mice received two full-thickness wounds. The wounds of the HCD group were covered with HCD, whereas those of the other groups were treated with 0.1 mL of the relevant type of honey, before being covered with HCD. Wound area was significantly smaller in the HCD group than in the Acacia + HCD and Manuka + HCD groups on day 13 and days 8–14, respectively. Moreover, compared with the HCD group, reepithelialization was delayed in the Acacia + HCD group and reepithelialization and collagen deposition were delayed in the Chinese milk vetch + HCD and Manuka + HCD groups. These results indicate that the combined use of Japanese honey and HCD does not promote cutaneous wound healing compared with the use of HCD alone. Thus, this method is probably not useful for promoting healing.


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