Ketanserin accelerates wound epithelialization and neovascularization

We investigated the acute effects of topical ketanserin, a 5-HT₂ (serotonin) receptor blocker, on wound epithelialization and vascularization with the use of the hairless mouse ear model. Varying concentrations of Ketanserin (0%, 0.2%, 2.0%, 20% weight/volume) were administered to standardized full-thickness skin wounds on the dorsum of the hairless mouse ear immediately after surgery and daily thereafter. With the use of video microscopy and computer-assisted planimetry, vascularization and epithelialization were traced every third day until the wounds were fully healed. Arteriole diameters at selected sites near the skin wound were measured before wound creation and after wounding. It was concluded that topically administered ketanserin significantly accelerates both the vascular ( p < 0.001 at 2% and 20% concentrations) and epithelial ( p < 0.001 at 20% concentration) rates of wound healing in full-thickness nonpathologic skin wounds. Vasodilation of terminal arterioles was not a major response to Ketanserin. Faster epithelialization was possibly due to direct effect of ketanserin on epithelial cells.     

The hairless mouse ear: an in vivo model for studying wound neovascularization

Microvascular ingrowth into damaged tissue is an essential component of the normal healing process. In fact, wound therapy is often aimed at promoting neovascularization. However, little is known about the mechanisms that regulate microvascular ingrowth into a healing wound. This limited knowledge is largely due to the lack of adequate models in which microvascular ingrowth can be quantitatively analyzed throughout the healing process. To address this deficiency, we developed a model in which a wound was created on the ear of the hairless mouse-a well established model for directly viewing and measuring skin microcirculation. While the animals were under ketamine and xylazine anesthesia, 2.25 mm diameter full-thickness wounds were created on the dorsum of hairless mouse ears down to but not including the cartilage (0.125 mm depth). With the use of video microscopy and computer-assisted digitized planimetry, the precise epithelial and neovascular wound edge was viewed and measured regularly throughout healing. Therefore, this model can provide objective data on wound epithelialization and neovascularization throughout healing. This model was used to examine the effect of topical wound agents on epithelialization and neovascularization. Differential effects by these anti-microbial agents on these two processes were observed, which suggests clinical implications for their use.     

Evaluation of wound healing effects of micronized acellular dermal matrix in combination with negative pressure wound therapy: In vivo study

Acellular dermal matrix (ADM) grafts can provide coverage for full-thickness skin defects and substitute for dermal defects. We tested the effectiveness of micronized ADM (mADM) as a dressing material, combined with negative pressure wound therapy (NPWT), for managing superficial wounds. We compared the wound healing effect of mADM in combination with NPWT with those of gelatin and mADM applied with a foam dressing. These therapeutic materials were applied to 36 cm² excisional wounds in a porcine full-thickness skin defect model. Wound healing kinetics and new tissue formation were assessed 10 days after the initial treatment by measuring the wound area. Collagen deposition and neovascularization were histologically evaluated. Compared with the other two groups, mADM plus NPWT combination group had a significantly larger wound area at the baseline (P = .0040), but the smallest on the 7th day (P = .0093). In addition, collagen formation and neovascularization were more histologically promoted than in the other two groups. mADM showed better results than the gelatin group but less collagen and revascularization than the combination group, and there was no significant difference in wound area. Our results show that the combination of mADM and NPWT has a synergistic wound healing effect.     

Full-thickness wounding of the mouse tail as a model for delayed wound healing: accelerated wound closure in Smad3 knock-out mice

Experimentally induced wounds in animal models are useful in gaining a better understanding of the cellular and molecular processes of wound healing, and in the initial evaluation of the safety and effectiveness of potential therapeutic agents. However, studying delayed healing has proved difficult in animals, whose wounds heal within a few days. In this report, we describe a novel method for establishing mouse wounds that require up to 3 weeks or more for complete closure, and we show the validity of this model in Smad3 null mice, which are known to display accelerated healing. Full-thickness wounds, measuring 0.3 by 1.0 cm, were made down to fascia on the dorsal aspect of the mouse tail in Smad3 knock-out mice and control littermates, approximately 1 cm distal to the body of the animal. The wounds were left to heal by secondary intention and were assessed histologically by computerized planimetry for wound closure at various times after wounding. The wounds in wild-type mice displayed delayed healing, with full closure occurring between 14 and 25 days after wounding. Complete closure of similar wounds in Smad3 null mice healed 30 percent faster (p < 0.01). By immunostaining for ki67, a marker for proliferation, Smad3 null animals also showed increased proliferation of dermal wound cells by day 4 after wounding. Cultured dermal fibroblasts from Smad3 null mice had increased baseline DNA synthesis and, interestingly, an enhanced response to transforming growth factor-beta1. By Western blot analysis, Smad3 null mice fibroblasts showed a compensatory increase in mitogen-activated protein kinase phosphorylation in response to transforming growth factor-beta1, suggesting that mitogen-activated protein kinase overcompensation together with loss of Smad3 may be involved in the modulation of faster healing. We conclude that this novel tail-wounding model may be useful for studying delayed wound closure.     

Research of PDGF-BB gel on the wound healing of diabetic rats and its pharmacodynamics

BACKGROUND: One of the leading causes of impaired wound healing is diabetes mellitus. In diabetic patients, a minor skin wound often leads to serious complications. Many experiments had demonstrated that the expression of platelet-derived growth factor (PDGF) and its receptor was decreased in wounds of healing-impaired diabetic mice, indicating that a certain expression level of PDGF is essential for normal repair. MATERIALS AND METHODS: The diabetic rats was induced by a single i.p. injection of streptozotocin and a 1.8 cm diameter full-thickness wound was made on each side of the rat mid-back. Then the rats were randomly divided into five groups, with eight animals in each group as follows: blank control, vehicle control, 3.5 microg PDGF-BB/cm(2) treatment group, 7 microg PDGF-BB/cm(2) treatment group and 14 microg PDGF-BB/cm(2) treatment group for either 7 or 14 consecutive days after wounding. Re-epithelialization area was measured by computerized planimetry, percentage wound closure and percentage wound contraction was calculated, granulation tissue and collagen formation was assessed by Masson trichrome, cell proliferation (proliferating cell nuclear antigen staining) and angiogenesis (Factor VIII related antigen staining) was assessed by immunohistological methods. RESULTS: PDGF-BB treatment improved healing quality, enhanced angiogenesis, cell proliferation and epithelialization, and formed thicker and more highly organized collagen fiber deposition in full-thickness excisional wound of diabetic rats. The effects of topically applied PDGF-BB were dose-dependent. CONCLUSIONS: PDGF-BB is an important future clinical tool, particularly for stimulating soft tissue repair in patients with an impaired capacity for wound healing.     

Expression of growth factors in early wound healing in rat skin

Growth factors are a group of hormone-like polypeptides that have been shown to play a central role in different phases of wound healing. The expression of these growth factors in early wound healing has not been quantified, and the pattern and distribution of these growth factors in early wound healing has not been described completely. Furthermore the quantity and pattern of distribution of these growth factors have not been investigated in early wounds produced by various methods of surgical incision. Comparison of the rate of healing between the CO₂ laser wound and the scalpel wound has produced conflicting results. The present immunohistochemical study uses polyclonal antibodies specific for epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor p (TGF-β), and basic fibroblast growth factor (bFGF) to observe the pattern and distribution of these growth factors in rat skin wound and elucidate whether there are differences in the expression of these growth factors which might account for the delayed healing of the CO₂ laser wounds compared to the scalpel as has been observed by some authors. Our results indicate that EGF, TGF-β, PDGF, and bFGF are expressed and distributed in same areas of the early skin wound. The area of expression of these growth factors was associated with presence of wound inflammatory cells and wound fibroblasts. Our study found that there were no significant differences in the expression of growth factors in the majority of time points between the CO₂ laser wounds and the scalpel wounds. © 1994 wiley-Liss, Inc.     

Exacerbated and prolonged inflammation impairs wound healing and increases scarring

Altered inflammation in the early stage has long been assumed to affect subsequent steps of the repair process that could influence proper wound healing and remodeling. However, the lack of explicit experimental data makes the connection between dysregulated wound inflammation and poor wound healing elusive. To bridge this gap, we used the established rabbit ear hypertrophic scar model for studying the causal effect of dysregulated inflammation. We induced an exacerbated and prolonged inflammatory state in these wounds with the combination of trauma‐related stimulators of pathogen‐associated molecular patterns from heat‐killed Pseudomonas aeruginosa and damage‐associated molecular patterns from a dermal homogenate. In stimulated wounds, a heightened and lengthened inflammation was observed based on quantitative measurements of IL‐6 expression, tissue polymorphonuclear leukocytes infiltration, and tissue myeloperoxidase activity. Along with the high level of inflammation, wound healing parameters (epithelial gap and others) at postoperative day 7 and 16 were significantly altered in stimulated wounds compared to unstimulated controls. By postoperative day 35, scar elevation of stimulated wounds was higher than that of control wounds (scar elevation index: 1.90 vs. 1.39, p < 0.01). Moreover, treatment of these inflamed wounds with Indomethacin (at concentrations of 0.01, 0.1, and 0.4%) reduced scar elevation but with adverse effects of delayed wound closure and increased cartilage hypertrophy. In summary, successful establishment of this inflamed wound model provides a platform to understand these detrimental aspects of unchecked inflammation and to further test agents that can modulate local inflammation to improve wound outcomes.     

Expectation‐induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial

Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation‐induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative ‘wound gel’ was applied on one of the two wounds, whereas a ‘non‐active gel’ was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non‐active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation‐induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers.     

Evaluations of bacterial contaminated full thickness burn wound healing in Sprague Dawley rats Treated with Tualang honey

Aim:

The effect of Tualang honey on wound healing in bacterial contaminated full-thickness burn wounds was evaluated in 36 male Sprague Dawley rats.

Materials and Methods:

The rats were randomly divided into three groups (n = 12/group). Three full-thickness burn wounds were created on each rat. Each group of rats was inoculated with a different organism in the burn wounds: Group A was inoculated with Pseudomonas aeruginosa, Group B was inoculated with Klebsiella pneumoniae and Group C was inoculated with Acinetobacter baumannii. One wound on each rat was dressed with either Tualang honey, Chitosan gel or Hydrofibre silver. Each wound size was measured on day 3, 6, 9, 12, 15, 18 and 21 of the study.

Results:

The mean wound size of the Tualang honey-treated wounds was not statistically different than that of the Chitosan gel or Hydrofibre silver-treated wounds when the wounds were compared throughout the entire experiment (P > 0.05). However, comparing the mean wound size on day 21 alone revealed that the Tualang honey-treated wounds were smaller in comparison to that of the Chitosan gel and Hydrofibre silver-treated groups.

Conclusions:

This study shows that topical application of Tualang honey on burn wounds contaminated with P. aeruginosa and A. baumannii gave the fastest rate of healing compared with other treatments.     

Bioactive peptide amphiphile nanofiber gels enhance burn wound healing

BackgroundBurns are physically debilitating and potentially fatal injuries. The standard-of-care for burn wounds is the coverage with gauze dressings designed to minimize trauma to the regenerating epidermis and dermis during dressing changes. However, deep partial- and full-thickness burns always heal slowly when standard wound care alone is performed. We have previously reported that peptide amphiphile (PA) gels, pH-induced self-assembling nanostructured fibrous scaffolds, promote cell proliferation and have great potential in regenerative medicine for rapid repair of tissues. In this study, we hypothesized that the PA gels are capable of accelerating wound healing in burn injury.MethodsArtificially generated thermally damaged fibroblasts and human umbilical vein endothelial cells were seeded onto the various PA nanofiber gels including bioactive and nonbioactive peptide sequences. Cell proliferation was assessed at different time points, and thermally damaged fibroblasts and HUVECs manifested increased proliferation with time when cultured with various PA gels. To determine in vivo effects, burn wounds of rats were treated with the bioactive Arg-Gly-Asp-Ser (RGDS)-modified gel that showed greater cell proliferation in vitro. The wound closure was observed, and skin samples were harvested for histologic evaluation.ResultsCell proliferation using the RGDS-PA gel was significantly higher than that observed in other gels. The RGDS-PA gel significantly enhanced re-epithelialization during the burn wound healing process between days 7 and 28. Application of PA gels accelerates the recovery of deep partial-thickness burn wounds by stimulation of fibroblasts and the creation of an environment conducive to epithelial cell proliferation and wound closure.ConclusionsThis biomaterial represents a new therapeutic strategy to overcome current clinical challenges in the treatment of injuries resulting from burns.     

明胶/聚己内酯电纺复合纳米纤维支架促进创面愈合的实验研究

目的 了解明胶/聚己内酯(Gt/PCL)电纺复合纳米纤维支架对家兔全层皮肤缺损创面愈合的影响. 方法 将16只家兔背部制作全层皮肤缺损创面,其中8只行同体对照实验,分别以Gt/PCL纳米纤维膜覆盖(Gt/PCL组)、PCL纤维膜覆盖(PCL组);余下8只家兔创面用凡士林纱布覆盖(对照组),各组创面数均为8个.记录创面愈合时间;于伤后3、7、10 d计算创面愈合率,并取创面及创周组织行组织病理学观察. 结果 Gt/PCL组创面愈合时间为(18.2±1.3)d、PCL组(20.3±1.1)d、对照组为(22.0±0.6)d,组间差异有统计学意义(P＜0.05);Gt/PCL组伤后各时相点创面愈合率均高于其他2组(P＜0.05).与其余2组比较,Gt/PCL组真皮层肉芽组织增生少,上皮细胞移行速度明显增快,胶原排列规则. 结论 Gt/PCL电纺复合纳米纤维支架能明显促进家兔全层皮肤缺损创面的愈合,是目前可供选择的效果比较确切的组织工程支架材料.     

Vaginal incisional wound healing in a rabbit menopause model: A histologic analysis

Intoduction and hypothesis

The vaginal wound healing process is a major determinant of surgical outcome following pelvic reconstructive surgery. Since the majority of these surgeries are performed in peri- and postmenopausal women, it is essential to understand how estrogen deficiency affects this process. We aimed to histologically evaluate the vaginal incisional wound healing process in a rabbit menopause model.

Methods

Sixty three rabbits were utilized and divided into 3 groups: Twenty one underwent bilateral oophorectomy, 21 underwent a sham surgery, and 21 served as controls. Eight weeks later, standardized full-thickness 6?mm circular segments were excised from the vagina of all rabbits and spontaneous healing was recorded. Animals were euthanized sequentially, before wounding, and at 0, 4, 7, 14, 21 and 35?days after wounding, and their wounds were harvested and assessed histologically for wound healing using a validated scoring system.

Results

Oophorectomized rabbits showed significantly delayed wound closure (p?<?0.02), neovascularization (p?<?0.01), granulation tissue accumulation and maturation (p?<?0.02), collagen deposition (p?<?0.01) and re-epithelialization (p?<?0.01), however acute and chronic inflammation were significantly enhanced (p?<?0.02).

Conclusion

Oophorectomized rabbits show protracted incisional vaginal wound healing by all histologic criteria, however, inflammation is significantly enhanced.     

Comparison of five dermal substitutes in full-thickness skin wound healing in a porcine model

The wound healing attributes of five acellular dermal skin substitutes were compared, in a two-step procedure, in a porcine model. Ten pigs were included in this experimental and randomized study. During the first step, dermal substitutes (Integra^®, ProDerm^®, Renoskin^®, Matriderm^® 2 mm and Hyalomatrix^® PA) were implanted into full-thickness skin wounds and the epidermis was reconstructed during a second step procedure at day 21 using autologous split-thickness skin graft or cultured epithelial autograft. Seven pigs were followed-up for 2 months and 3 pigs for 6 months. Dermal substitute incorporation, epidermal graft takes, wound contraction and Vancouver scale were assessed, and histological study of the wounds was performed.     

Potential of Oncostatin M to accelerate diabetic wound healing

Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti‐inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full‐thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left‐side wounds (n = 10) and phosphate‐buffered saline was applied on the two right‐side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM‐treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P < 0·05). The results of this study indicate that topical application of OSM may have the potential to accelerate healing of diabetic wounds.     

Adenoviral-mediated gene transfer of insulin-like growth factor 1 enhances wound healing and induces angiogenesis

Background

Chronic wounds are characterized by a wound healing and neovascularization deficit. Strategies to increase neovascularization can significantly improve chronic wound healing. Insulin-like growth factor (IGF)-1 is reported to be a keratinocyte mitogen and is believed to induce angiogenesis via a vascular endothelial growth factor (VEGF)-dependent pathway. Using a novel ex vivo human dermal wound model and a diabetic-impaired wound healing murine model, we hypothesized that adenoviral overexpression of IGF-1 (Ad-IGF-1) will enhance wound healing and induce angiogenesis through a VEGF-dependent pathway.

Methods

Ex vivo: 6-mm full-thickness punch biopsies were obtained from normal human skin, and 3-mm full-thickness wounds were created at the center. Skin explants were maintained at air liquid interface. Db/db murine model: 8-mm full-thickness dorsal wounds in diabetic (db/db) mice were created. Treatment groups in both human ex vivo and in vivo db/db wound models include 1 × 10⁸ particle forming units of Ad-IGF-1 or Ad-LacZ, and phosphate buffered saline (n = 4–5/group). Cytotoxicity (lactate dehydrogenase) was quantified at days 3, 5, and 7 for the human ex vivo wound model. Epithelial gap closure (hematoxylin and eosin; Trichrome), VEGF expression (enzyme-linked immunosorbent assay), and capillary density (CD 31 + CAPS/HPF) were analyzed at day 7.

Results

In the human ex vivo organ culture, the adenoviral vectors did not demonstrate any significant difference in cytotoxicity compared with phosphate buffered saline. Ad-IGF-1 overexpression significantly increases basal keratinocyte migration, with no significant effect on epithelial gap closure. There was a significant increase in capillary density in the Ad-IGF-1 wounds. However, there was no effect on VEGF levels in Ad-IGF-1 samples compared with controls. In db/db wounds, Ad-IGF-1 overexpression significantly improves epithelial gap closure and granulation tissue with a dense cellular infiltrate compared with controls. Ad-IGF-1 also increases capillary density, again with no significant difference in VEGF levels in the wounds compared with control treatments.

Conclusions

In two different models, our data demonstrate that adenoviral-mediated gene transfer of IGF-1 results in enhanced wound healing and induces angiogenesis via a VEGF-independent pathway. Understanding the underlying mechanisms of IGF-1 effects on angiogenesis may help produce novel therapeutics for chronic wounds or diseases characterized by a deficit in neovascularization.     

Wound-healing outcomes using standardized assessment and care in clinical practice.

INTRODUCTION: Wound-healing outcomes applying standardized protocols have typically been measured within controlled clinical trials, not natural settings. Standardized protocols of wound care have been validated for clinical use, creating an opportunity to measure the resulting outcomes. PURPOSE: Wound-healing outcomes were explored during clinical use of standardized validated protocols of care based on patient and wound assessments. DESIGN: This was a prospective multicenter study of wound-healing outcomes management in real-world clinical practice. METHOD: Healing outcomes from March 26 to October 31, 2001, were recorded on patients in 3 long-term care facilities, 1 long-term acute care hospital, and 12 home care agencies for wounds selected by staff to receive care based on computer-generated validated wound care algorithms. After diagnosis, wound dimensions and status were assessed using a tool adapted from the Pressure Sore Status Toolfor use on all wounds. Wound, ostomy, and continence nursing professionals accessed consistent protocols of care, via telemedicine in home care or paper forms in long-term care. A physician entered assessments into a desktop computer in the wound clinic. Based on evidence that healing proceeds faster with fewer infections in environments without gauze, the protocols generally avoided gauze dressings. RESULTS: Most of the 767 wounds selected to receive the standardized-protocols of care were stage III-IV pressure ulcers (n = 373; mean healing time 62 days) or full-thickness venous ulcers (n = 124; mean healing time 57 days). Partial-thickness wounds healed faster than same-etiology full-thickness wounds. CONCLUSIONS: These results provide benchmarks for natural-setting healing outcomes and help to define and address wound care challenges. Outcomes primarily using nongauze protocols of care matched or surpassed best previously published results on similar wounds using gauze-based protocols of care, including protocols applying gauze impregnated with growth factors or other agents.     

Turmeric (Curcuma longa) rhizome paste and honey show similar wound healing potential: a preclinical study in rabbits

The potential efficacy of fresh turmeric (Curcuma longa) paste to heal wounds was tested in a preclinical study in an animal model. Turmeric paste was compared with honey as a topical medicament against a control on experimentally created full-thickness circular wounds in 18 rabbits (Oryctolagous cuniculus). Wound healing was assessed on the basis of physical, histomorphological, and histochemical parameters on treatment days 0, 3, 7, and 14. Only tensile strength was measured on day 14 of treatment. It was observed that the wound healing was statistically significantly faster (P < .01) in both treatment groups compared to the control group.     

The effects of the helium neon laser on wound healing in rabbits and on human skin fibroblasts in vitro

Helium-neon laser irradiation was applied to the denuded dermis and full-thickness open wounds on rabbit skin and cell cultures of human skin fibroblasts to investigate its effects on the wound healing process. To determine the effects of He-Ne laser radiation on epithelialization rate, 3×3 cm denuded dermis areas on the flank of 16 rabbits were irradiated daily until complete epithelialization occurred. For histopathological evaluation biopsies were taken on the first day and on the day on which epithelialization was complete. As a second part of in vivo study, identical full-thickness skin wounds were created bilaterally on the middle flank area of 12 rabbits. He-Ne laser irradiation was applied daily to the wounds until complete healing occurred to determine the effects of the low-energy laser on the contraction of open wounds. The contralateral wounds were left untreated, serving as controls. In a separate in vitro study, the effect of single or multiple applications of He-Ne laser irradiation on normal human skin fibroblasts in cell cultures was evaluated using growth measurement. The mean epithelialization time was 11±0.63 days for the laser-treated wounds and 12±0.12 days for the control wounds. The difference was not significant. No significant difference was found between the contraction rates of the full-thickness wounds (e.g., on the seventh postoperative day, the average wound area was 70.2±6.75% of original wound area in the laser-treated group and 66.±8.75% in the control group). Histopathologically, epidermal thickening and an increase in dermal vascularity were observed in healed wounds of the laser-treated groups. However, in vitro, this low-energy laser promoted cell growth in human fibroblast cell cultures in 2-and 3-day treated groups (p>0.05).     

Wound tensile strength and contraction rate are not affected by laparotomy or pneumoperitoneum

Background: Many cellular elements responsible for wound healing are affected by laparotomy. The aim of this study was to evaluate the effects of laparotomy and CO₂ pneumoperitoneum on wound healing. Methods: Male Sprague Dawley rats were randomly assigned to one of three experimental groups. Anesthesia control rats underwent no procedure. Pneumoperitoneum group rats were insufflated with CO₂ gas. Laparotomy group rats underwent a 7-cm midline laparotomy incision. The interventions were 30 min long. For the incisional study (n= 30), a 4-cm dorsal full-thickness skin incision was made on each rat and then closed with staples. On postoperative days 7 and 14, an equal number of rats were sacrificed from each group, and wound tensile strength measurements were performed. For the excisional study (n= 45), each group of 15 rats underwent a 2-cm diameter circular dorsal full-thickness skin excision. Blinded measurements of wound area were performed every other day until wounds closed. Results: Wound tensile strength values were not significantly different among experimental groups at either time point. The study had a power of 80% to find a 30% difference at POD 7 and a power of 80% to find a 23% difference at POD 14 to a confidence level of p < 0.05. Wound contraction data from the excisional model were analyzed with the Generalized Estimation Equations statistical approach. When we modeled the treatment group as a covariate, no statistical difference was found between groups, demonstrating equal slopes across time. Conclusions: From the results of these studies, we conclude that wound healing in this model is not significantly diminished following laparotomy or peritoneal insufflation, as compared to anesthesia control. Received: 26 September 1997/Accepted: 27 January 1998     

Both dermal matrix and epidermis contribute to an inhibition of wound contraction

Contracture is a major detriment to functional recovery from large wounds. To determine the relative value of dermal replacement and epidermal coverage in inhibiting wound contraction, five full-thickness wounds (all 5 x 5 cm2) were placed on the back of 8 swine and treated in the following manner: (1) open wound, (2) porcine acellular dermis (analogous to AlloDerm for human use), (3) porcine acellular dermis with epidermal autograft placed 7 days postwounding, (4) porcine acellular dermis with immediate epidermal autograft, and (5) conventional-thickness autograft. Scar dimensions and punch biopsies were taken at days 14 and 30 postwounding. The planimetry results demonstrated that wound contraction was significantly greater with the open wounds (group 1) than all other wounds with a dermal substitute. Furthermore, wounds with initial epidermal coverage had significantly less contraction than unepithelialized wounds (14.8 +/- 1.1 cm2 at day 14 in wound group 2 vs. 20.4 +/- 0.6 cm2 in wound group 4; p < 0.05). Biopsy results revealed that wounds with initial epithelial coverage had the least amount of inflammation. These findings suggest that both dermal matrix and epidermal coverage contribute to an inhibition of wound contraction and that prompt epithelial coverage appears to impede contraction by reducing inflammation.