Acute Cutaneous Wound Healing Research Articles

Effect of pomegranate peel with/without autologous bone marrow on healing of acute cutaneous wounds in alloxan-induced diabetic rabbits.

Healing of bum wounds is commonly associated with many complications. Every year various new repair materials are developed and experimentally used for treating burn wounds. Humans with diabetes mellitus usually suffer from chronic wound healing. Vascular, neuropathic, immune function, and biochemical abnormalities each contribute to the altered tissue repair. One underlying factor that accompanies all diabetic ulcerations is poor vascular flow, a circumstance that impedes proper wound healing. Numerous studies have highlighted the importance of adequate vascular sufficiency and vessel proliferation in tissue repair and the lack thereof in diabetic wound healing. Other studies have looked at whether disarrayed capillary remodeling and maturation of vessels might play a role in impaired diabetic wound healing. This investigation has been planned to report the influence of treatment with a mixture of both the powder of pomegranate peel (PP) accompanied with an autologous bone marrow (BM) on the cure of burn injuries in experimentally induced diabetic rabbits. Alloxan monohydrate has been applied to create diabetes in 50 rabbits. Then in each rabbit, two deep second-degree burn wounds were experimentally created. The animals were then divided randomly into 5 treatment sections: non-treatment controls (C1), treated with an available commercial powder for wound (C2), treatment with powder of PP, treatment with alone BM, and the final group treated with PP powder with bone marrow (PPBM). The speed of wound closure and the histopathological changes during healing were measured. The levels of the biomarkers of rabbit platelet-derived growth factor AA (PDGF-AA) and rabbit protease-activated receptor 1 (PAR-1) were measured on days 0, 4, 8, and 12. Wound healing was markedly more rapid in all the treatment groups versus the control non-treated group. Interestingly, a rapid wound cure was significantly observed in the PPBM group versus the other treatment ones. The histological assessment clarified a significant elevation in the fibroblast and collagen scores in the PPBM group versus the other sections. In addition, there were significant increases in the serum levels of the biomarkers PDGF-AA and PAR-1 among groups. Dependent on the results of current research, it can be concluded that both PP powder with BM PPBM significantly accelerate the healing process of burn wounds in experimentally induced diabetic rabbits.

Maintaining and Restoring Gradients of Ions in the Epidermis: The Role of Ion and Water Channels in Acute Cutaneous Wound Healing.

Significance: Aquaporins and ion channels establish and regulate gradients of calcium, sodium, potassium, chloride, water, and protons in the epidermis. These elements have been found to play significant roles in skin biology and wound healing. In this study, we review our understanding of these channels and ion gradients, with a special emphasis on their role in acute wound healing. Recent Advances: Specifically, we assess the temporal and spatial arrangements of ions and their respective channels in the intact skin and during wound and healing to provide a novel perspective of the role of ionic gradients through the various stages of wound healing. Critical Issues: The roles of gradients of ions and channels in wound healing are currently not well understood. A collective analysis of their traits and arrangements in the skin during wound healing may provide a new perspective and understanding of the functionality of gradients of ions and channels in skin biology and wound healing. Future Directions: It is important to elucidate how the gradients of ions and ion channels regulate and facilitate wound healing. A better understanding of the ionic environments may identify novel therapeutic targets and improved strategies to promote wound healing and possibly treat other cutaneous diseases.

Author Correction: Hyaluronic acid accelerates re-epithelialization and healing of acute cutaneous wounds.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27(3 Suppl): 37-45. doi: 10.26355/eurrev_202304_31320-PMID:37129334-published online on April 27, 2023. After publication, the authors found some transcription mistakes and applied minor corrections to the Abstract and Discussion sections. The sections have been amended as follows: - Abstract section: "an average 80% decrease" has been corrected in "an average 86% decrease"; "a small amount of exudate was noted in 91% of wounds" has been corrected in "a small amount of exudate was noted in 10% of wounds". - Discussion section: "by a reduced wound surface area of 80% at six weeks and a reduced surface area of 95% after eight weeks" has been corrected to "by a reduced wound surface area of 80% at four weeks and a reduced surface area of 86% after six weeks". There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/31320.

Hyaluronic acid accelerates re-epithelialization and healing of acute cutaneous wounds.

Hyaluronic acid has been efficient in ameliorating and supporting recovery in both chronic and acute lesions. The aim of this study was to assess the effectiveness of hyaluronic acid-based cream and gauze pads in cutaneous wounds. This retrospective and prospective study examines the use of a 0.2% hyaluronic acid cream or gauze-pads application (Connettivina Bio®). 85 patients participated in the study and were affected by wounds of different etiologies, comprising superficial trauma wounds (20), surgical sutures (15), first- and second-degree burns (15), dermabrasions (30) and ulcers of different etiologies (5). We analyzed the healing process in terms of progression and wound quality. Moreover, we performed biopsies (not on all patients) to evaluate the grade of re-epithelialization. We observed a reduction in the mean surface area of the wounds, precisely 456 mm2 at baseline to 147 mm2 after six weeks with an average 86% [corrected] decrease in the wound surface area. No fibrin tissue was observed, and a small amount of exudate was noted in 10% [corrected] of wounds. Hyaluronic acid cream and gauze-pads-based treatments were well tolerated by patients. All groups showed a decrease of inflammation with a progressive increase of collagen fibers and granulation tissue. The treatment with hyaluronic acid 0.2% yielded remarkable outcomes in the re-epithelialization of superficial wounds and provided favorable recovery and tolerance for patients.

Animal models for the study of acute cutaneous wound healing.

The process of wound healing is critical to maintaining homeostasis after injury. Although a considerable amount has been learned about this complex process, much remains unknown. Whereas, studies with human volunteers are ideal given the unique nature of the human skin anatomy and immune system, the lack of such clinical access has made animal models prime candidates for use in preclinical studies. This review aims to discuss the strengths and limitations of the commonly used mammalian species in wound healing studies: murine, rabbit and porcine. Thereafter, a survey of models of various acute wounds such as cutaneous, ear, and implant are presented and representative studies that use them are described. This review is intended to acquaint readers with the vast spectrum of models available, each of which has a distinct utility. At the same time, it highlights the importance of utilising clinical samples to complement investigations conducted in animal models. Through this strategy, it is hoped that forthcoming research may be more reflective of the acute wound healing process as it occurs in humans.

NLRC3 deficiency promotes cutaneous wound healing due to the inhibition of p53 signaling

Cutaneous wound healing is a complicated process that is characterized by an initial inflammatory phase followed by a proliferative phase. NLRC3 plays important roles in innate immunity, inflammatory regulation and tumor cell growth. However, the function of NLRC3 in wound healing remains unclear. Here, we investigated the function of NLRC3 in acute cutaneous wound healing using Nlrc3 gene knockout (Nlrc3−/−) mice. Our results demonstrated that skin wound repair in Nlrc3−/− mice was significantly accelerated compared with that in wild-type (WT) mice. NLRC3 deficiency promoted the inflammatory and proliferative phases in wounds enhanced the inflammatory response and increased re-epithelialization and granulation tissue formation, and these phenotypes were primarily ascribed to regulatory effects on p53 signaling. Mechanistically, we uncovered novel crosstalk between NLRC3 and p53 signaling and revealed that NLRC3 could mediate the ubiquitination and degradation of p53 in an Hsp90-dependent manner. In conclusion, our study suggests that NLRC3 is a critical negative regulator of the inflammatory response and cell proliferation during wound healing and that blocking NLRC3 may represent a potential approach for accelerating wound healing.

A Biomimetic Composite Bilayer Dressing Composed of Alginate and Fibroin for Enhancing Full-Thickness Wound Healing.

Full-thickness skin wound dressings are critically important for acute cutaneous wound healing. In this study, a bilayer sheet originating from biological macromolecules, mimicking skin hierarchy structure is developed. This sheet is composed of a steady silk fibroin (SF)/sodium alginate (SA) composite scaffold as the bottom regenerative layer and a SA film as the protective top layer. Scanning electron microscope analysis revealed the thickness of the top layer is ≈25µm and is tightly adhered to the composite scaffold layer with interconnected pores (≈150µm). The bilayer sheets are displayed suitable water uptake capacity and high stability in water. The mass retention percentage of the bilayer sheets is ≈50% during three weeks of PBS degradation in vitro. The tensile strength of the bilayer sheets is significantly increased from 13.41±3.75kPa (single scaffold) to 59.81±5.98kPa. The composite scaffolds are more conducive to the growth and proliferation of human dermal microvascular endothelial cells. The experiment results in vivo are demonstrated superior and faster epithelialization and dermal regeneration in the wound treated with bilayer sheets because the sheets are accelerated wound closure, reduced the inflammatory response, and promoted protein synthesis in the extracellular matrix and blood vessel ingrowth.

A systematic review of autologous adipose-derived stromal vascular fraction (SVF) for the treatment of acute cutaneous wounds.

Stromal vascular fraction (SVF), derived enzymatically or mechanically from adipose tissue, contains a heterogenous population of cells and stroma, including multipotent stem cells. The regenerative capacity of SVF may potentially be adapted for a broad range of clinical applications, including the healing of acute cutaneous wounds. To evaluate the available literature on the efficacy and safety of autologous adipose-derived stromal vascular fraction (SVF) for the treatment of acute cutaneous wounds in humans. A systematic review of the literature utilizing MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify published clinical trials of autologous adipose-derived SVF or similar ADSC-containing derivatives for patients with acute cutaneous wounds. This was supplemented by searches for ongoing clinical trials through ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. 872 records were initially retrieved. Application of inclusion and exclusion criteria yielded 10 relevant studies: two completed non-randomized controlled trials and eight ongoing clinical trials. Both completed studies reported a statistically significant benefit in percentage re-epithelialization and time to healing for the SVF treatment arms. Safety information for SVF was not provided. Ongoing clinical trials were assessing outcomes such as safety, patient and observer reported scar appearance, wound healing rate, and wound epithelization. In the context of substantial limitations in the quantity and quality of available evidence, the existing literature suggests that SVF may be a useful treatment for acute cutaneous wounds in humans. More clinical trials with improved outcome measures and safety assessment are needed.

Pulmonary infection interrupts acute cutaneous wound healing through disruption of chemokine signals

Abstract Individuals who are hospitalized with traumatic injuries are susceptible to nosocomial pneumonia. While the effect of the injury on pulmonary infection has been examined in many contexts, it is less well understood how lung infection affects healing wounds. To address this, we examined the outcomes of laparotomized patients with and without pneumonia using the American College of Surgeons NSQIP database. Individuals who developed pneumonia were twice as likely to experience wound dehiscence compared to those without pneumonia. We hypothesized that the immune response could not to meet the demands of competing inflammatory insults in the skin and lungs. To examine this, we developed murine models of post-operative lung infection. Mice were wounded by the dorsal subcutaneous implantation of polyvinyl alcohol (PVA) sponges or tail skin excision, then infected intranasally with Klebsiella oxytoca. PVA sponge wounds allow for the examination of cellular and cytokine responses during acute wound healing, while wound closure can be measured with the tail skin excision model. Pulmonary infection led to rapid suppression of wound IL-1α, IL-1β, and chemokines. This was followed by decreased accumulation of innate leukocytes in the wound and delayed wound closure. In contrast, lung antibacterial responses were not affected by the presence of surgical wounds. Wound healing in infected mice could be rescued by the addition of the chemokines CCL2 and CXCL1; however, this treatment caused a delay in bacterial clearance in the lungs. These data suggest that the immune response is not fully equipped to respond to disparate and competing inflammatory insults, which could have implications beyond the setting of post-operative pneumonia.

Topical Applications of Thiosulfinate-Enriched Allium sativum Extract Accelerates Acute Cutaneous Wound Healing in Murine Model.

To determine whether topical applications of thiosulfinate-enriched Allium sativum extract (TASE) can accelerate acute cutaneous wound healing (WH) in a murine model. Keratinocyte viability and in vitro wound closure were assessed in keratinocyte cultures. Effects of topical TASE (0.5 μg/mL of allicin in 97% ethanol) on acute cutaneous WH were determined in a murine model of acute cutaneous wound. Twelve mice were alternately assigned to the vehicle- and TASE-treated groups (n=6 per group). Expression levels of mRNA for keratinocyte differentiation marker-related proteins (filaggrin, loricrin and involucrin) and lipid synthetic enzymes (elongation of very long chain fatty acids protein 4 (ELOVL4), fatty acid synthase (FA2H), 3-hydroxy- 3-methyl-glutaryl-coenzyme A reductase (HMGCoA), and serine palmitoyltransferase (SPT)) were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding, while transepidermal water loss (TEWL) rates were measured in wounded areas. TASE accelerated WH both in vivo (40% vs. 22% reduction in wound area, P<0.01) and in vitro (90% vs. 65% reduction in wound area, P<0.01). Moreover, topical applications of TASE upregulated the expression levels of epidermal mRNA for ELOVL4, HMGCoA, SPT, filaggrin, loricrin and involucrin (P<0.05 vs. vehicle-treated controls) on day 3 after wounding. Likewise, TASE significantly lowered TEWL rates in comparison with vehicle alone on day 8 (33.06±2.09 g/(m2·h) vs. 24.60±2.04 g/(m2·h), P<0.01). Topical applications of TASE stimulated keratinocyte proliferation and formation of epidermal permeability barrier function, leading to acceleration of acute cutaneous WH. Topical products containing TASE could be used to manage acute cutaneous WH.

Effects of pure and ozonated sunflower seed oil (Helianthus annuus) on hypergranulation tissue formation, infection and healing of equine lower limb wounds

This study was undertaken to evaluate the therapeutic effects of topical application of pure sunflower seed oil (oil group) and ozonated sunflower seed oil (ozone group) on acute cutaneous wound healing in eight healthy horses. The control group was treated with 0.9% sodium chloride. Two wounds were surgically produced on each horse on the proximal epiphysis of the metacarpus on the dorsal aspect of each forelimb. Wound area and contraction were measured on days 0, 3, 7, 14 and 21. Biopsy samples were taken to evaluate epithelial hyperplasia, inflammation, exuberant granulation tissue, exudate type, angiogenesis, and fibroplasia. Culture swabs were also collected. Wound contraction at 21 days for the oil group was 52.68%, for the ozone group was 72.16%, and for the control group (0.9% sodium chloride) was 34.80%. The ozone group had a significantly smaller wound size and a residual wound area than the control and the oil groups, on days 14 and 21. The control-wounds and oil-wounds had suppurative exudate and the presence of Streptococcus zooepidemicus. Neutrophilic inflammatory infiltrate was observed in all groups. Granulation tissue was observed on day 7 in all groups, but exuberant granulation tissue was observed only in the control group on days 14 and 21. Reepithelialization was observed on day 14 in the ozone group. In conclusion, these results demonstrate that topical application of ozonated sunflower seed oil accelerates acute cutaneous wound repair in horses, preventing hypergranulation tissue and infection, and that it is superior to treatment with pure sunflower seed oil and 0.9% sodium chloride.

653 Topical use of exosomes from human maternal milk accelerates acute cutaneous wound healing

653 Topical use of exosomes from human maternal milk accelerates acute cutaneous wound healing

Chemokine ligand\u2013receptor interactions critically regulate cutaneous wound healing

BackgroundWound healing represents a dynamic process involving directional migration of different cell types. Chemokines, a family of chemoattractive proteins, have been suggested to be key players in cell-to-cell communication and essential for directed migration of structural cells. Today, the role of the chemokine network in cutaneous wound healing is not fully understood. Unraveling the chemokine-driven communication pathways in this complex process could possibly lead to new therapeutic strategies in wound healing disorders.MethodsWe performed a systematic, comprehensive time-course analysis of the expression and function of a broad variety of cytokines, growth factors, adhesion molecules, matrixmetalloproteinases and chemokines in a murine cutaneous wound healing model.ResultsStrikingly, chemokines were found to be among the most highly regulated genes and their expression was found to coincide with the expression of their matching receptors. Accordingly, we could show that resting and activated human primary keratinocytes (CCR3, CCR4, CCR6, CXCR1, CXCR3), dermal fibroblasts (CCR3, CCR4, CCR10) and dermal microvascular endothelial cells (CCR3, CCR4, CCR6, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3) express a distinct and functionally active repertoire of chemokine receptors. Furthermore, chemokine ligand–receptor interactions markedly improved the wound repair of structural skin cells in vitro.ConclusionTaken together, we here present the most comprehensive analysis of mediators critically involved in acute cutaneous wound healing. Our findings suggest therapeutic approaches for the management of wound closure by targeting the chemokine network.

Effect of topically applied Saccharomyces boulardii on the healing of acute porcine wounds: a preliminary study.

BackgroundNormal wound healing progresses through a series of interdependent physiological events: inflammation, angiogenesis, re-epithelialization, granulation tissue formation and extracellular matrix remodeling. Alterations in this process as well as the bacterial type and load on a wound may alter the wound healing rate. The purpose of this study was to evaluate the effect of topical Saccharomyces boulardii on the healing of acute cutaneous wounds, using a prospective, controlled, experimental study, with six purpose bred landrace pigs.ResultsAll wounds healed without apparent complications. Comparison of the mean 3D and 2D wound surface area measurements showed no significant difference between treatment groups as wounds decreased similarly in size over the duration of the study. A significant reduction in wound surface area was identified sooner using 3D assessments (by day 9) compared to 2D assessments (by day 12) (P < 0.001). There was no significant effect of treatment group on the number of multiple isolates or the most common isolates obtained relative to control wounds. There was no histologically appreciable difference between the wounds of the different groups.ConclusionsTopical application of Saccharomyces boulardii does not hasten wound healing or change the wounds’ microbiome under the conditions reported in this study.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-2012-8) contains supplementary material, which is available to authorized users.

Effect of Hevea brasiliensis latex sap gel on healing of acute skin wounds induced on the back of rats

to evaluate the effect of topical delivery of latex cream-gel in acute cutaneous wounds induced on the back of rats. we subjected sixteen rats to dermo-epidermal excision of a round dorsal skin flap, with 2.5cm diameter. We divided the animals into two groups: Latex Group: application of cream-gel-based latex throughout the wound bed on postoperative days zero, three, six and nine; no treatment on the wound. Photographs of the lesions were taken on the procedure day and on the 6th and 14th postoperative days, for analyzing the area and the larger diameter of the wound. We carried out euthanasia of all animals on the 14th postoperative day, when we resected he dorsal skin and the underlying muscle layer supporting the wound for histopathological study. there was no statistically significant difference in the percentage of wound closure, in the histopathological findings or in the reduction of the area and of the largest diameter of the wounds among the groups studied on the 14th postoperative day. according to the experimental conditions in which the study was conducted, latex cream-gel did not interfere in the healing of acute cutaneous wounds in rats.

Genetic Deletion of Galectin-3 Does Not Impair Full-Thickness Excisional Skin Healing

Galectin-3 has been linked to the regulation of several molecular processes essential during acute cutaneous wound healing, but a comprehensive study of the role of galectin-3 has yet to be performed. With known roles in macrophage polarization, myofibroblast differentiation, re-epithelialization, and angiogenesis, we hypothesized that genetic deletion of galectin-3 would significantly impair healing of excisional skin wounds in mice. In wild-type mice, galectin-3 expression correlated temporally with the inflammatory phase of healing. Conversely, genetic deletion of galectin-3 did not alter gross wound healing kinetics even though it resulted in delayed re-epithelialization. Wound composition was not altered up to 15 days after wounding in knockout mice, and isolated dermal fibroblast function invitro was unchanged. We further explored, spatially, the expression of galectin-3 in human chronic wound tissue in relation to the immune cell infiltrate. We show a decreased mRNA and protein abundance in the wound edge tissue, whereas markers of neutrophils, M1 and M2 macrophages are expressed abundantly. Both transforming growth factor-β1 and tumor necrosis factor-α decrease galectin-3 mRNA abundance in chronic wound edge dermal fibroblasts invitro, providing a potential mechanism for this decreased expression in chronic wounds.

Sodium Butyrate Plus EGF and PDGF-BB Aids Cutaneous Wound Healing in Diabetic Mice

Topical application of growth factors is known to aid defective and/or delayed wound healing in diabetic patients. In this study, the effect of topical application of sodium butyrate (Na-Bu), EGF, and PDGF-BB was analysed on the acute cutaneous wound healing in streptozotocin (STZ) induced diabetic mouse model. Two cutaneous wounds were created, one on each of the dorsolateral sides of the diabetic mice. Na-Bu, EGF, and PDGF-BB were applied to the wound either individually or in various combinations. The wound healing was monitored visually and scored as percentage wound closure. The tissue samples were collected from the wound site at 1, 7, and 14 days after wounding from the treated and untreated diabetic wounds and analysed for the levels of EGF-R, β-PDGF-R, HDAC1, p21, and phosphorylated and hypophosphorylated pRb proteins. Our results indicate that application of EGF plus PDGF-BB at the initial stages followed by subsequent addition of Na-Bu along with these growth factors helps wound healing in diabetic mice. It appears that, in addition to cell proliferative agents, a cell differentiation agent, Na-Bu, is necessary for diabetic wound healing. Topical application of EGF plus PDGF-BB along with Na-Bu could be developed as therapeutic agents to treat and manage human diabetic wounds.

Electrospun polyurethane-dextran nanofiber mats loaded with Estradiol for post-menopausal wound dressing

Post-menopausal wound care management is a substantial burden on health services, since there are an increased number of elderly populations linked with age-related delayed wound healing. The controlled estrogen replacement can accelerate healing of acute cutaneous wounds, linked to its potent anti-inflammatory activity. The electrospinning technique can be used to introduce the desired therapeutic agents to the nanofiber matrix. So here we introduce a new material for wound tissue dressing, in which a polyurethane–dextran composite nanofibrous wound dressing material loaded with β-estradiol was obtained through electrospinning. Dextran can promote neovascularization and skin regeneration in chronic wounds. This study involves the characterization of these nanofibers and analysis of cell growth and proliferation to determine the efficiency of tissue regeneration on these biocomposite polymer nanofibrous scaffolds and to study the possibility of using it as a potential wound dressing material in the in vivo models.

Topical tacrolimus does not negatively impact acute skin wound healing

Despite the increasing use of topical tacrolimus, there is little information about its effect on skin wound healing. To determine effects on acute cutaneous wound healing, two full-thickness skin wounds were imparted on the backs of 45 hairless mice, which were then divided into vehicle-, topical tacrolimus- and topical steroid-treated group. Each drug was topically applied once daily. The wound area was assessed by using dermoscopic images every two days after wounding. At 3, 7 and 11 days after wounding, 10 wounds in each group were collected for semi-quantitative analysis of histological features including re-epithelialization, polymorphonuclear leucocytes, fibroblasts and collagen. We also checked the mRNA expression levels of EGF, TGF-β, TNF-α and IL-1α. While topical application of clobetasol propionate was found to delay re-epithelialization and infiltration of polymorphonuclear leucocyte, topical treatment with tacrolimus showed patterns similar to that of the vehicle. In the tacrolimus-treated group, mRNA expression levels of IL-1α and TGF-β were slightly decreased, while the others were similar with the vehicle-treated group. Unlike steroid, topical tacrolimus, therefore, did not disturb the wound healing process in a murine skin wound model.

Estrogen promotes cutaneous wound healing via estrogen receptor β independent of its antiinflammatory activities

Post-menopausal women have an increased risk of developing a number of degenerative pathological conditions, linked by the common theme of excessive inflammation. Systemic estrogen replacement (in the form of hormone replacement therapy) is able to accelerate healing of acute cutaneous wounds in elderly females, linked to its potent antiinflammatory activity. However, in contrast to many other age-associated pathologies, the detailed mechanisms through which estrogen modulates skin repair, particularly the cell type–specific role of the two estrogen receptors, ERα and ERβ, has yet to be determined. Here, we use pharmacological activation and genetic deletion to investigate the role of both ERα and ERβ in cutaneous tissue repair. Unexpectedly, we report that exogenous estrogen replacement to ovariectomised mice in the absence of ERβ actually delayed wound healing. Moreover, healing in epidermal-specific ERβ null mice (K14-cre/ERβL2/L2) largely resembled that in global ERβ null mice. Thus, the beneficial effects of estrogen on skin wound healing are mediated by epidermal ERβ, in marked contrast to most other tissues in the body where ERα is predominant. Surprisingly, agonists to both ERα and ERβ are potently antiinflammatory during skin repair, indicating clear uncoupling of inflammation and overall efficiency of repair. Thus, estrogen-mediated antiinflammatory activity is not the principal factor in accelerated wound healing.