Document Type : Original Article

Authors

1 Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical sciences, Mashhad, Iran

2 Department of Emergency Medicine, Mazandaran University of Medical sciences, Sari, Iran

3 Department of Emergency Medicine, Mashhad University of Medical sciences, Mashhad, Iran

4 Department of Emergency Medicine, Faculty of Medicine, Shahroud University of Medical sciences, Shahroud, Iran

5 Department of Emergency Medicine, Faculty of Medicine, Birjand University of Medical sciences, Birjand, Iran

6 Department of Emergency Medicine, Faculty of Medicine, Mazandaran University of Medical sciences, Sari, Iran

Abstract

Objective: To examine the relationship between wounding-to-door time and wound healing duration in patients with simple traumatic wounds admitted to Shahid Rajaei Emergency Department (ED) in Tonekabon city during the COVID-19 pandemic.
Methods: This was a prospective longitudinal study on patients with simple traumatic wounds referred to ED of Shahid Rajaei Hospital in Tonekabon from April to the end of September 2021 were examined for demographics, trauma to hospital door, and body mass index. Patients were followed for wound healing for a month. Data was analyzed by considering the wound healing time as the primary outcome.
Results: There were 142 were males and 45 were females. The mean age of the subjects was 32.24±18.25. The mean wound-to-door time was 4.3±2.7 hours. The maximum and minimum wound-to-door time was 17 hours and 1 hour, respectively. The average wound healing duration was 14.3±3.6 days. A significant positive correlation was found between the wound healing duration and wound-to-door time (r= 0.435, P<0.001). When analyzing subgroups of patients based on the BMI, antibiotic use, smoking status, and some wound locations, there was no significant correlation between wound healing duration and wounding-to-door time (P>0.05). 
Conclusion: This study revealed that delayed visit of ED for receiving proper wound care would be associated with increased wound healing duration; while this relationship is being modified by smoking status, using antibiotics, and the BMI.

Graphical Abstract

Wounding-To-Door Time Metrics Outcome of Traumatic Simple Wounds in Emergency Department

Keywords

Main Subjects

Introduction

Wounds are scratches, crevices, lacerations, or traumatic injuries to the skin which may remain intact but the bottom of the skin is usually red or bruised [1]. Injuries can be divided into closed and open, while cuts and lacerations on the skin are open and bruises are closed injuries [2]. Approximately 7 million traumatic wounds occur each year and 26 to 90 million wounds cause by surgical incisions. Open wounds and lacerations are the third most common problems in the ED accounting for approximately 8 million emergency department referrals in the United States each year [3]. Wound healing is a complex process that occurs in distinct, yet overlapping, highly coordinated stages, while hemostasis or coagulation is the first stage of the body's response to the skin laceration [3-4]. Wound healing is a dynamic and complex tissue response to injury and it is generally a regular phenomenon. This response requires interactions between different cell types, scleroprotein, growth factors, and proteases. Special cell types initially keep the injury site clean, and then gradually form a scaffold to fill the resulting defects. Factors such as soluble growth factors and extracellular matrix are the most important ones in the wound healing process. Besides, physical factors such as the generated forces by cell deformation are involved in this process [5-6]. Various factors can impact the wound healing process. These factors include the patientsold age, hypoxia, anemia, hypoperfusion, diabetes, uremia, obesity, malnutrition, chemotherapy and radiotherapy, inactivity, cardiovascular as well as metabolic diseases, and taking various drugs (corticosteroids, anticoagulants, anti-cancer, aspirin, colchicine, penicillamine, cyclosporine, and phenyl) [7-9]. Wounds made with a surgical razor heal faster than those with jagged edges and severe necrosis. Therefore, the lateral surfaces of the wound have an important effect on the nature and speed of wound healing. Poor blood supply due to various diseases can affect the speed of wound healing. For instance, atherosclerosis or vascular obstruction impairs wound healing. Since the wound healing process is perfectly dependent on blood circulation and blood cells, the lack of blood supply can disrupt this process [10]. Wound management is one of the most vital efforts in the ED [3]. When a patient refers to the ED, the size, precise location, depth, and shape of the wound and identification of a foreign body should be checked and recorded. Deep and wide wounds should be managed in the operating room with more complete facilities and under sufficient light. Wounds are usually managed with a moist dressing, wound dressing, and suturing, or covering [11]. The results of recent studies have shown that dressings should be designed to prevent crust formation on the wound to avoid cell migration. Dressing with an exudate absorbent coating or with a non-stick coating such as Vaseline gauze is helpful to prevent crust formation. Many physicians and researchers believe that the disinfectant solution is toxic to lymphocytes and fibroblasts which are essential cells for wound healing. The use of substances such as povidone-iodine or Betadine, acetic acid, and hydrogen peroxide is not suggested. The only commercial solution approved by the Food and Drug Administration is a saline buffer [5, 12]. Wound infection is one of the most important medical problems that delays wound healing. Wound infection loosens the abdominal sutures and hernia repair sutures. Wound opening and hernia recurrence are other complications of wound infection. Infection also affects the wound sight and causes the wound looks nasty or delays wound healing. Wounds that do not heal within 3 months are considered chronic. Skin wounds in damaged or non-vascular tissues are also chronic and are considered chronic ulcers [8, 13]. Knowing the potential barriers and risk factors for abnormal wound healing can help you properly prevent, diagnose, and treat large, problematic wounds [14]. Regarding the current situation and the lack of sufficient evidence for the relationship between wounding-to-door time and various factors, including wound healing duration, the present study investigated the relationship between wounding-to-door time and wound healing duration of simple wounds in patients referred to Shahid Rajaei ED in Tonekabon city during COVID-19 pandemic in 2021.

Method

This was a prospective cohort study in which all patients who were referred to the ED of Shahid Rajaei Hospital in Tonekabon city from April to the end of September 2021 due to simple traumatic wounds were examined. Inclusion criteria included adult patients with trauma and complete patient records, and exclusion criteria included patients with a history of chronic diseases such as diabetes, taking immunosuppressive, hypertension, immunodeficiency, corticosteroids drugs, alcohol consumption, and a complex wound that requires hospitalization. The final statistical population of the study consisted of 187 patients. All stages of this study were conducted with the approval of the Research Council and the Ethics Committee of Mazandaran University of Medical Sciences (IR.MAZUMS.RIB.REC.1400.021).

The patients were interviewed, clinically examined, and their demographic and clinical variables (age, gender, education degree, smoking, scar site, obesity, and body mass index (BMI)) were recorded by using a checklist. According to the official WHO table, the subjects included in the study were classified based on their BMI.

The criterion of wounding-to-door time was the patient's report and based on the time of ulceration until arriving at ED. Patients conditions were followed up daily and the complete wound healing and suture removal times were recorded. All examinations, treatments, and follow-ups were performed by one physician during the Covid-19 epidemic.

After data gathering and recording them in SPSS 22, a statistical method was selected based on the type of variables. Pearson and Spearman analysis methods were used to investigate the correlation coefficient between quantitative variables with normal and abnormal distributions, respectively. Quantitative data were expressed as mean and standard deviation as a percentage and the difference was higher than P <0.05.

Results

A total of 187 patients, 142 males (75.94%) and 45 females (24.06%) were chosen as the statistical population of the study. The subjects mean age was 32.24 ± 18.25 years old. The youngest subject was aged 18 and the oldest was 90. According to the chart below, approximately 76% of the participants were males. According to Table 1, approximately 60 subjects (32%) were smoker and most of the participants had high school degrees or lower (about 30%) and the highest percentages of participantsbody mass index (BMI) were in normal weight (32.62%) and overweight (32.08%).

Regarding the studied subjects, 23% of them were classified as obese. Therefore, based on the criteria mentioned in Table 1, the highest percentage (13.4%) was classified in the first group (Obese class 1). According to the reported results, approximately 35% of the participants had wounds on their heads.

Wounding-to-door time in the subjects was 4.3± 2.7 hours on average, while the maximum and minimum wound lives were 17 and 1 hour, respectively. Regarding the wound healing duration, the total mean was 14.3± 3.6 days, while it was 14 ±3.4 days in males, and 15.1. ± 4.1 days in females. It should be noted that this period has been reported on average 14.2± 3.5 days in participants under 50 and 15.6 ±3.9 days in participants over 50 years old. In this study, a significant relationship was found between wound healing duration and wounding-to-door time (P < 0.001). Figure 1 displays a direct correlation between wounding-to-door time and wound healing duration.

The results of analyzing the relationship between wound healing duration and wounding-to-door time based on wound site are reported in the following table. Based on Table 2, there is a statistically significant relationship between wound healing duration and wounding-to-door time in the upper limb (P = 0.014) and hand (P = 0.001), and no significant relationship was found in the lower limb (P = 0.113), head (P = 0.255), and leg (P = 0.335). Likewise, a direct correlation was found between the wound healing duration and wounding-to-door time in the upper limbs (Pearson = 0.435) and hands (Pearson = 0.510).

Table 1: Demographic Characteristics of Patients with Simple Traumatic Wounds

Variable

Frequency (percentage)

Age

18.25±32.24

Gender

Female

45(24.06)

Male

142 (75.94)

Smoking

Yes

60 (32.09)

No

127 (67.91)

Level of education

Illiterate

16 (8.51)

Lower than high school

55 (29.41)

High school degree

50 (26.73)

College degree

19 (10.16)

Bachelor

46 (24.59)

Ma/Ms

1 (0.53)

BMI

Underweight

23 (12.29)

Normal weight

61 (32.62)

Overweight

60 (32.08)

Obese

43 (22.99)

Obesity

Obese class 1

25 (13.4)

Obese class 2

16 (8.6)

Obese class 3

2 (1.1)

Wound site

Upper limb

21 (16.57)

Lower limbs

34 (18.18)

Head

65 (34.75)

Hand

40 (21.39)

Leg

17 (9.09)


Figure 1: Correlation Diagram of Wound Healing Duration (days) and Wound Age (hours)

Table 2: Relationship between Wound Age and Wound Healing Duration based on the Studied Variables

 

Number of observations

Pearson Correlation

P-value

Total

187

.435*

0.014

Wound location

Upper limb

31

0.277

0.113

Lower limb

34

0.143

0.255

Head

65

.510**

0.001

Hand

40

0.249

0.335

Leg

17

.393**

0.001

Gender

Male

142

.396**

0.007

Female

45

.374**

0.001

Age

Younger than 50 years old

161

.512**

0.007

Older than 50 years old

26

0.473

0.054

Education level

Illiterate

16

.480**

0.001

Lower than high school degree

55

.311*

0.028

High school degree

50

.520*

0.023

College degree

19

.342*

0.02

Bachelor degree

46

.393**

0.001

Taking antibiotics

183

0.602

0.398

Not taking antibiotics

4

0.306

0.058

Smoking

60

.440**

0.001

Non-smoking

127

0.167

0.448

BMI

Underweight

23

.357**

0.005

Normal weight

61

.515**

0

Overweight

60

0.271

0.079

Obsess

43

-0.026

0.902

Obesity

Class I

25

0.434

0.093

           

 

Regarding the gender effect on wound healing duration and wounding-to-door time, a significant relationship was reported between wound healing duration and wounding-to-door time, and it was obtained at (P = 0.000) in males and (P = 0.007) in females with a direct correlation in males (Pearson = 0.393) and females (Pearson = 0.396). Besides, a significant relationship was found between wound healing duration and wounding-to-door time in the age group over 50 (P = 0.007) and under 50 (P = 0.000). Thus, there is a correlation between wound healing duration and wounding-to-door time in the age group over 50 (Pearson = 0.374) and under 50 (Pearson = 0.512).

According to the results of this study, there is a statistically significant relationship and a direct correlation between wound healing duration and wounding-to-door time regarding the participant's level of education (P <0.05), while the strongest significant relationship was reported in participants with high school and lower degrees (P = 0.000). Thus, the longer the wound lasts, the longer it takes to heal in this group of participants. Regarding two factors of smoking and taking antibiotics, there was a significant relationship between wound healing duration and wounding-to-door time (P = 0.000) and non-smoking (P = 0.000) with a correlation between wounding-to-door time with wound healing duration based on antibiotic use (Pearson = 0.393) and non-smoking (Pearson = 0.440). After examining the relationship between wound healing duration and wounding-to-door time regarding the patients' body mass index, a significant relationship was found between wound healing duration and wounding-to-door time regarding the normal weight (P = 0.005) and overweight (P = 0.000). According to Pearson's correlation coefficient, there is a direct correlation between wounding-to-door time and wound healing duration regarding participants with normal weight (Pearson = 0.357) and overweight (Pearson = 0.515). In line with the performed analysis, the relationship between wound healing duration and wounding-to-door time based on obese class was also investigated and no significant relationship was found (P >0.05).

Discussion

The present study aimed to investigate the relationship between the wounding-to-door time of a simple traumatic wound and the duration of wound healing in patients referred to the ED of Shahid Rajjaei Hospital in Tonekabon City during the COVID-19 pandemic. The findings of this study indicated that the mean wound healing duration was shorter in male than in female patients. However, the results of a study by Marie Kjaer et al. (2018) revealed that wound healing duration was slower in males than in females [17], while the results of this study are in line with the results of the study conducted by Christopher G. et al. [18].

Another study by Hardman (2008) reported that the difference in gene expression between the wounds of old men and young men was regulated almost exclusively by estrogen. Estrogen affects wound healing by regulating a variety of genes associated with regeneration, matrix production, protease inhibition, epidermal function, and genes primarily associated with inflammation. Gilliver (2007) concluded that estrogen can increase age-related disorders in wound healing in males and females, while androgens negatively regulate skin wound healing [19, 20]. In our study, the mean duration of wound healing in participants aged over 50 was longer than in ones under 50 and this result was in line with the results of the study conducted by Christopher G. et al. [18].

The relationship between smoking and delayed wound healing in clinical practice is obvious, while no extensive controlled studies have been yet performed. The documented effects of the toxic components of cigarette smoke- particularly nicotine, carbon monoxide, and hydrogen cyanide- suggest potential mechanisms by which smoking may prevent rapid wound healing. According to the study conducted in our study, approximately 68% of the studied participants were non-smokers. Data analysis revealed a significant relationship between wound healing duration and wound age in non-smokers [21]. Lvarez-Jiménez et al. (2014) carried out a study in which the healing duration of burn wounds in smokers and non-smokers were compared and the obtained results were consistent with the results of our study [22].

According to the results of our study, the wound healing duration and wound age are interrelated with the level of education of the participants, while the most significant relationship was observed in participants with lower than high school degree. Thus in this group, the longer a wound lives, the longer it takes to heal. However, this relationship is almost weak in terms of correlation. It should be noted that participants of different ages participated in this study which may affect the obtained results.

Many complications may result from partial hypoperfusion and ischemia in the subcutaneous adipose tissue. This condition can also be caused by reduced delivery of antibiotics. In surgical wounds, the increased tension on the wound edges that is frequently seen in obese patients also contributes to wound dehiscence. Furthermore, the results of our study reveal that approximately 33% of the studied participants were categorized in the normal class in terms of BMI. According to the analysis on participants with normal BMI and overweight, the results are as follows: a significant relationship was found in both categories, but according to the Pearson coefficient reported in the tables, a more correlation was found between wound healing duration and wound age in the BMI category of the overweight. Therefore, in overweight patients, the longer the wound lasts, the longer it takes to heal. The adverse effects of adipokines on the systemic immune response appear to affect the wound healing process. Peripheral blood mononuclear cell dysfunction decreased lymphocyte proliferation, and altered peripheral cytokine levels have been reported in obesity. Hence, many obesity-related changes in peripheral immune system function improve with weight loss [23, 24].

In our study, the relationship between wound healing duration and wound age in the subjects was investigated. Hence, a significant relationship was observed between the wound healing duration and wound age (P <0.05). Minor scratches may not be uncomfortable; however, they usually heal within 3 to 7 days. The larger and deeper the scratches, the longer it takes to heal. It may take 7 to 10 days for a large, deep wound to heal [25]. In 1988, Berk et al. examined 372 patients with traumatic wounds at Jamaica Hospital. In this prospective observational study, wound healing wound edge detachment or wound infection were examined. Analysis of data based on wound site showed that wound healing duration in the head area was not related to wound age [26]. In our study, approximately 35% of the participants had wounds on their heads. There was a significant relationship between wound healing duration and wound age regarding the site of wounds in the upper limbs and hands. Therefore, no significant relationship was observed between wound age and wound healing duration on the head.

According to the results of previous studies, oral antibiotics of cephalexin reduce the rate of infection and increase wound healing. Various studies have also emphasized the importance of a moist wound environment in accelerating wound healing [27]. The results of a clinical trial conducted in 2017 showed that the use of oral antibiotics cephalexin and metronidazole in obese female patients has reduced the duration of wound healing. The results of our study revealed that the wounding-to-door time and wound healing duration can be modified based on the use of antibiotics. Other studies have indicated that taking antibiotics reduced wound healing duration and this result is consistent with the results of our studies [28].

Limitations

In this study, correlation statistics and covariates were used for data stratification to re-analyze the correlation and this limited our data interpretation to determine how those factors modifying correlations between the wound healing duration and wound to door of ED time affect the wound healing time. Thus, further studies are needed with logistic models.

Conclusion

Our study revealed that delayed visit of ED to receive proper wound care would be associated with increased wound healing duration; while this relationship is being modified by smoking status, using antibiotics, some wound locations, and the BMI.

Funding

This research did not receive any specific grant from fundig agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.

Conflict of Interest

There are no conflicts of interest in this study.

ORCID:

Roohie Farzaneh

https://www.orcid.org/0000-0002-0892-0155

Fatemeh Maleki

https://www.orcid.org/0000-0001-9760-2611

Mahdi Foroughian

https://www.orcid.org/0000-0002-3944-9361

HOW TO CITE THIS ARTICLE

Roohie Farzaneh, Mohadese Arvan, Nazgol Khodaie, Sara Rahsepar, Arman Hakemi, Fatemeh Maleki, Mahdi Foroughian, Somayyeh Ahmadnezhad, Wounding-To-Door Time Metrics Outcome of Traumatic Simple Wounds in Emergency Department. J. Med. Chem. Sci., 2023, 6(2) 304-312

https://doi.org/10.26655/JMCHEMSCI.2023.2.11

URL: http://www.jmchemsci.com/article_155937.html

[1]. Menon G.K., New insights into skin structure: scratching the surface, Advanced drug delivery reviews, 2002, 54:S3 [Crossref], [Google Scholar], [Publisher]
[2]. Bowler P., Duerden B., Armstrong D.G., Wound microbiology and associated approaches to wound management, Clinical microbiology reviews, 2001, 14:244 [Crossref], [Google Scholar], [Publisher].
[3]. Ghanem E., Heppert V., Spangehl M., Abraham J., Azzam K., Barnes L., Matsen L., Morris M.J., Purtill J.J., Ranawat C., Sharkey P.F., Sierra R., Stefansdottir A., Wound management, The Journal of arthroplasty, 2014, 29:84 [Crossref], [Google Scholar], [Publisher]
[4]. Webb L.X., New techniques in wound management: vacuum-assisted wound closure, JAAOS-Journal of the American Academy of Orthopaedic Surgeons, 2002, 10:303 [Google Scholar], [Publisher]
[5]. MacKay D.J., Miller A.L., Nutritional support for wound healing, Alternative medicine review, 2003, 8:359 [Google Scholar], [Publisher]
[6]. Kirsner R.S., Eaglstein W.H., The wound healing process, Dermatologic clinics, 1993, 11:629 [Crossref], [Google Scholar], [Publisher]
[7]. Velnar T., Bailey T., Smrkolj V., The wound healing process: an overview of the cellular and molecular mechanisms, Journal of International Medical Research, 2009, 37:1528 [Crossref], [Google Scholar], [Publisher]
[8]. Enoch S., Leaper D.J., Basic science of wound healing, Surgery (Oxford), 2008, 26:31 [Crossref], [Google Scholar], [Publisher]
[9]. Li J., Chen J., Kirsner R., Pathophysiology of acute wound healing, Clinics in dermatology, 2007, 25:9 [Crossref], [Google Scholar], [Publisher]
[10]. Stojadinovic O., Pastar I., Gordon K.A., Tomic-Canic M., Physiology and pathophysiology of wound healing in diabetes, The diabetic foot: Springer, 2012, 127 [Crossref], [Google Scholar], [Publisher].
[11]. Otrock Z.K., Mahfouz R.A., Makarem J.A., Shamseddine A.I., Understanding the biology of angiogenesis: review of the most important molecular mechanisms, Blood Cells, Molecules, and Diseases, 2007, 39:212 [Crossref], [Google Scholar], [Publisher]
[12]. Carmeliet P., Jain R.K., Molecular mechanisms and clinical applications of angiogenesis, Nature, 2011, 473:298 [Crossref], [Google Scholar], [Publisher].
[13]. Rittié L., Cellular mechanisms of skin repair in humans and other mammals, Journal of cell communication and signaling, 2016, 10:103 [Crossref], [Google Scholar], [Publisher]
[14]. Schultz G.S., Sibbald R.G., Falanga V., Ayello E.A., Dowsett C., Harding K., Romanelli M., Stacey M.C., Teot L., Vanscheidt W., Wound bed preparation: a systematic approach to wound management, Wound repair and regeneration, 2003, 11:S1 [Crossref], [Google Scholar], [Publisher]
[15]. Brunicardi F., Andersen D., Billiar T., Dunn D., Hunter J., Matthews J., Pollock R., Schwartz's principles of surgery, 2014, 10e:1034, McGraw-hill [Google Scholar], [Publisher]
[16]. Naska S., Yuzwa S.A., Johnston A.P., Paul S., Smith K.M., Paris M., Sefton M.V., Datti, Miller F.D., Kaplan D.R., Identification of drugs that regulate dermal stem cells and enhance skin repair, Stem cell reports, 2016, 6:74.84 [Crossref], [Google Scholar], [Publisher]
[17]. Elbay R.Y., Kurtulmuş A., Arpacıoğlu S., Karadere E., Depression, anxiety, stress levels of physicians and associated factors in Covid-19 pandemics, Psychiatry research, 2020, 290:113130 [Crossref], [Google Scholar], [Publisher]
[18]. Morgan W.J., Hutchison D., Johnson H.M., The delayed treatment of wounds of the hand and forearm under antibiotic cover, The British journal of surgery, 1980, 67:140 [Crossref], [Google Scholar], [Publisher]
[19]. Berk W.A., Osbourne D.D., Taylor D.D., Evaluation of the 'golden period' for wound repair: 204 cases from a Third World emergency department, Annals of emergency medicine, 1988, 17:496 [Crossref], [Google Scholar], [Publisher]
[20]. Baker M.D., Lanuti M., The management and outcome of lacerations in urban children, Annals of emergency medicine, 1990, 19:1001 [Crossref], [Google Scholar], [Publisher]
[21]. Lammers R.L., Hudson D.L., Seaman M.E., Prediction of traumatic wound infection with a neural network-derived decision model, The American journal of emergency medicine, 2003, 21:1 [Crossref], [Google Scholar], [Publisher]
[22]. van den Baar M.T., van der Palen J., Vroon M.I., Bertelink P., Hendrix R., Is time to closure a factor in the occurrence of infection in traumatic wounds? A prospective cohort study in a Dutch level 1 trauma centre, Emergency medicine journal, 2010, 27:540 [Crossref], [Google Scholar], [Publisher]
[23]. Zehtabchi S., Tan A., Yadav K., Badawy A., Lucchesi M., The impact of wound age on the infection rate of simple lacerations repaired in the emergency department, Injury, 2012, 43:1793 [Crossref], [Google Scholar], [Publisher]
[24]. Waseem M., Lakdawala V., Patel R., Kapoor R., Leber M., Sun X., Is there a relationship between wound infections and laceration closure times?, International journal of emergency medicine, 2012, 5:32 [Crossref], [Google Scholar], [Publisher]
[25]. Kjaer M., Kristjánsdóttir H., Andersen L., Heegaard A.M., Ågren M.S., Jorgensen L.N., The effect of gender on early colonic anastomotic wound healing, International journal of colorectal disease, 2018, 33:1269 [Crossref], [Google Scholar], [Publisher]
[26]. Engeland C.G., Sabzehei B., Marucha P.T., Sex hormones and mucosal wound healing, Brain, behavior, and immunity, 2009, 23:629 [Crossref], [Google Scholar], [Publisher]
[27]. Hardman M.J., Ashcroft G.S., Estrogen, not intrinsic aging, is the major regulator of delayed human wound healing in the elderly, Genome biology.,2008, 9:R80 [Crossref], [Google Scholar], [Publisher]
[28]. Gilliver S.C., Ashworth J.J., Ashcroft G.S., The hormonal regulation of cutaneous wound healing, Clinics in dermatology, 2007, 25:56 [Crossref], [Google Scholar], [Publisher]