Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes‐induced foot ulcer

Nitroglycerin (NTG) is an organic nitrate rapidly denitrated by enzymes to release free radical nitric oxide and shows improved wound healing and tissue protection from oxidative damage. The purpose of this study was to evaluate whether topical application of NTG in the form of gel/ointment along with a natural wound healing agent, aloe vera, would bring about wound healing by using diabetes‐induced foot ulcer model and rat excision wound model. All these formulations were evaluated for pH, viscosity, drug content and ex vivo diffusion studies using rat skin. Based on ex vivo permeation studies, the formulation consisting of carbopol 974p as a gelling agent and aloe vera was found to be suitable. The in vivo study used streptozotocin‐induced diabetic foot ulcer and rat excision wound models to analyse wound healing activity. The wound size in animals of all treated groups was significantly reduced compared with that of the diabetic control and marketed treated animals. This study showed that the gel formed with carbopol 974p (1%) and aloe vera promotes significant wound healing and closure in diabetic rats compared with the commercial product and provides a promising product to be used in diabetes‐induced foot ulcer.     

Wound healing activity of methanolic stem extract of Musa paradisiaca Linn. (Banana) in Wistar albino rats

This study is designed to explore the phytochemical, antibacterial and wound healing activity of methanolic stem extract of Musa paradisiaca Linn. (Banana). The phytochemical analysis was performed for the methanolic stem extract of Musa paradisiaca Linn. Results indicates that the Musa paradisiaca Linn. was rich in glucosides, tannins and alkaloids, saponins, flavonoids and phenols were present in moderate quantities. The extract shows antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus with the zone of inhibition of Pseudomonas aeruginosa was 21 mm and Staphylococcus aureus was 19 mm at concentration of 500 µg/disc. The minimum inhibitory concentration (MIC) was also evaluated for the extract. Wistar albino rats were selected for wound healing activity. The burn wound was created by using red hot steel rod from above the hind limb region. The methanolic extract was applied on the wound and the progressive changes were monitored every day. The wound contraction rate was absorbed based on the histopathological examination. It was concluded that the methanolic extract of Musa paradisiaca Linn. showed greater healing activity compared to control in Wistar albino rats.     

Epidermal growth factor‐containing wound closure enhances wound healing in non‐diabetic and diabetic rats

Background: This study was designed to elucidate the in vivo efficacy of epidermal growth factor (EGF) on wound healing in non diabetic and diabetic rats. Methods: Ninety‐six male Wistar‐Albino rats were randomly divided into six groups. Saline‐moistened gauze, pure gelatin or EGF in gelatin‐microsphere dressings were used in a dermal excision model in both normal and streptomycin‐induced diabetic rats. Wound healing was evaluated on day 7 and 14. Reduction in wound area, hydroxypyroline content and tensile strength of the wound were evaluated in each rat. Tissue samples taken from the wounds were examined histopathologically for reepithelialisation, cellular infiltration, number of fibroblasts, granulation and neovascularisation. Results: On day 7, the use of EGF‐containing dressing was observed to reduce the wound area better when compared with the other dressings tested. This effect was significant in normal rats rather than diabetic rats. The difference in reduction of wound area did not persist on day 14. No significant effect on hydroxyproline content of the wound was found with EGF‐containing dressing in either normal or diabetic rats. There was a statistically significant increase in tensile strength values of EGF‐applied non diabetic rats over the 14 day period. An increase in tensile strength was prominent in also EGF‐applied diabetic rats on day 14. Histological examination revealed higher histopathologic scores in EGF‐applied diabetic and non diabetic rats. Conclusion: These findings implicate that use of EGF in gelatin‐microsphere dressings improves wound healing both in normal and diabetic rats.     

A poly‐herbal formulation accelerates normal and impaired diabetic wound healing

In the present study, a poly‐herbal formulation (PHF) was prepared by combining the aqueous lyophilized leaf extracts of Hippophae rhamnoides L. and Aloe vera L. and the ethanol rhizome extract of Curcuma longa L., in an optimized ratio (1 : 7 : 1). The efficacy of PHF treatment was studied in normal and impaired diabetic rats using a full‐thickness cutaneous wound model. Topical PHF treatment increased cellular proliferation and collagen synthesis at the wound site in normal rats, as evidenced by the significant increase in DNA, total protein, hydroxyproline, and hexosamine contents in comparison with a positive control treated with a povidone–iodine ointment. The histological examinations and matrix metalloproteinases expression also correlated well with the biochemical findings, confirming the efficacy of PHF in normal wounds. In the streptozotocin‐induced diabetic rats, PHF treatment increased hydroxyproline and hexosamine content. A faster wound contraction was also observed in PHF‐treated normal and diabetic rats. The PHF also promoted angiogenesis as evidenced by an in vitro chick chorioallantoic membrane model and in vivo up‐regulated vascular endothelial growth factor expression. The results suggest that PHF possesses significant wound healing potential in both normal as well as chronic diabetic wounds.     

Characterisation of impaired wound healing in a preclinical model of induced diabetes using wide‐field imaging and conventional immunohistochemistry assays

Major complications of diabetes lead to inflammation and oxidative stress, delayed wound healing, and persistent ulcers. The high morbidity, mortality rate, and associated costs of management suggest a need for non‐invasive methods that will enable the early detection of at‐risk tissue. We have compared the wound‐healing process that occurs in streptozotocin (STZ)‐treated diabetic rats with non‐diabetic controls using contrast changes in colour photography (ie, Weber Contrast) and the non‐invasive optical method Spatial Frequency Domain Imaging (SFDI). This technology can be used to quantify the structural and metabolic properties of in‐vivo tissue by measuring oxyhaemoglobin concentration (HbO₂), deoxyhaemoglobin concentration (Hb), and oxygen saturation (StO₂) within the visible boundaries of each wound. We also evaluated the changes in inducible nitric oxide synthase (iNOS) in the dermis using immunohistochemistry. Contrast changes in colour photographs showed that diabetic rats healed at a slower rate in comparison with non‐diabetic control, with the most significant change occurring at 7 days after the punch biopsy. We observed lower HbO₂, StO₂, and elevated Hb concentrations in the diabetic wounds. The iNOS level was higher in the dermis of the diabetic rats compared with the non‐diabetic rats. Our results showed that, in diabetes, there is higher level of iNOS that can lead to an observed reduction in HbO₂ levels. iNOS is linked to increased inflammation, leading to prolonged wound healing. Our results suggest that SFDI has potential as a non‐invasive assessment of markers of wound‐healing impairment.     

Wound‐healing potential of an ethanol extract of Carica papaya (Caricaceae) seeds

Carica papaya L. (Linn) (Caricaceae) is traditionally used to treat various skin disorders, including wounds. It is widely used in developing countries as an effective and readily available treatment for various wounds, particularly burns. This study evaluated the wound‐healing and antimicrobial activity of C. papaya seed extract. Ethanol extract of C. papaya seed (50 mg/kg/day) was evaluated for its wound‐healing activity in Sprague‐Dawley rats using excision wound model. Animals were randomly divided into four groups of six each (group 1 served as control, group 2 treated with papaya seed extract, group 3 treated with a standard drug mupirocin and papaya seed extract (1:1 ratio) and group 4 treated with a mupirocin ointment. Rate of wound contraction and hydroxyproline content were determined to assess the wound‐healing activity of the seed extract. The group 2 animals showed a significant decrease in wound area of 89% over 13 days when compared with groups 1 (82%), 3 (86%) and 4 (84%) respectively. The hydroxyproline content was significantly higher with the granulation tissue obtained from group 2 animals which were treated with C. papaya seed extract. Histological analysis of granulation tissue of the group 2 animals showed the deposition of well‐organized collagen. The extract exhibited antimicrobial activity against Salmonella choleraesuis and Staphylococcus aureus. Our results suggest that C. papaya promotes significant wound healing in rats and further evaluation for this activity in humans is suggested.     

Comparison of human umbilical cord blood‐derived mesenchymal stem cells with healthy fibroblasts on wound‐healing activity of diabetic fibroblasts

Various types of skin substitutes composed of fibroblasts and/or keratinocytes have been used for the treatment of diabetic ulcers. However, the effects have generally not been very dramatic. Recently, human umbilical cord blood‐derived mesenchymal stromal cells (hUCB‐MSCs) have been commercialised for cartilage repair as a first cell therapy product using allogeneic stem cells. In a previous pilot study, we reported that hUCB‐MSCs have a superior wound‐healing capability compared with fibroblasts. The present study was designed to compare the treatment effect of hUCB‐MSCs with that of fibroblasts on the diabetic wound healing in vitro. Diabetic fibroblasts were cocultured with healthy fibroblasts or hUCB‐MSCs. Five groups were evaluated: group I, diabetic fibroblasts without coculture; groups II and III, diabetic fibroblasts cocultured with healthy fibroblasts or hUCB‐MSCs; and groups IV and V, no cell cocultured with healthy fibroblasts or hUCB‐MSCs. After a 3‐day incubation, cell proliferation, collagen synthesis levels and glycosaminoglycan levels, which are the major contributing factors in wound healing, were measured. As a result, a hUCB‐MSC‐treated group showed higher cell proliferation, collagen synthesis and glycosaminoglycan level than a fibroblast‐treated group. In particular, there were significant statistical differences in collagen synthesis and glycosaminoglycan levels (P = 0·029 and P = 0·019, respectively). In conclusion, these results demonstrate that hUCB‐MSCs may have a superior effect to fibroblasts in stimulating diabetic wound healing.     

Topical embryonic stem cells enhance wound healing in diabetic rats

The effects of embryonic stem cells (ESCs) on diabetic wound healing were investigated using an excisional skin wound model in 110 diabetes‐induced rats. We transplanted a clonal population of ESCs (5 × 10⁶) by topical injection into full thickness skin wounds. Four study groups were used; nondiabetic rats as a control, non‐insulin controlled diabetic rats not treated with ESCs, insulin controlled diabetic rats not treated with ESCs, and insulin controlled diabetic rats treated with ESCs. Five rats in each experimental group were sacrificed on days 1, 5, 10, 15, and 20 after wounding. Wounds images were acquired daily and wound sizes were calculated. We measured the mRNA levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and fibronectin levels in extracellular matrix, and assessed wound healing by assessing histological parameters of epidermal regeneration, granulation tissue thickness, and angiogenesis. In the ESC‐treated group, wound sizes were significantly smaller than in the insulin controlled diabetic group not treated with ESCs on days 5 and 10 (p < 0.05), and EGF and VEGF levels were markedly higher on days 5 and 10, fibronectin levels on day 5 after injection. All histological scores in the ESC‐treated group were significantly higher than those of the insulin controlled diabetic group on day 5 (p < 0.05). Our results shows that topical ESCs enhance diabetic wound healing during the early stage, and suggest that ESCs transplantation offers a novel therapeutic modality for the treatment of diabetic wounds. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1554–1562, 2011     

Efficacy of Annona squamosa on wound healing in streptozotocin‐induced diabetic rats

Annona squamosa L. (Annonaceae), commonly known as custard apple, mainly used for its edible fruit, is also recognised with numerous medicinal properties. As there is no report on the efficacy of this plant for wound healing, we examined the efficacy of ethanolic extract of A. squamosa leaves on wound repair in streptozotocin–nicotinamide‐induced diabetic rats. Open excision wounds were made on the back of rats. The drug at a dosage of 100 mg/kg body wt was reconstituted in 200 µl of phosphate buffered saline and applied topically once daily for the treated wounds. The control wounds were left untreated. Wound tissues formed on days 4, 8, 12 and 16 (post‐wound) were used to estimate DNA, total protein, total collagen, hexosamine and uronic acid. Levels of lipid peroxides were also evaluated along with tensile strength and period of epithelialisation. A. squamosa L. increased cellular proliferation and collagen synthesis at the wound site as evidenced by increase in DNA, protein and total collagen. The treated wounds were observed to heal much faster as proved by enhanced rates of epithelialisation and wound contraction, which was also confirmed by histopathological examinations. The results strongly substantiate the beneficial effects of the topical application of A. squamosa L. in the acceleration of normal and diabetic wound healing.     

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.     

Hypoandrogenism related to early skin wound healing resistance in rats

The purpose of this study was to verify the effect of testosterone depletion on healing of surgical skin wounds at different ages and post‐operative periods. Forty‐four Wistar male rats were divided into four groups: Group 1Y (n = 11) – young control, sham‐operated rats (30‐day old); Group 1A (n = 10) – adult control, sham‐operated rats (3 to 4‐month old); Group 2Y (n = 10) – young rats after bilateral orchiectomy; and Group 2A (n = 11) – adult rats after bilateral orchiectomy. After 6 months, a linear incision was performed on the dorsal region of the animals. The resistance of the wound healing was measured in a skin fragment using a tensiometer, on the 7th and 21st post‐operative days. The wound healing resistance was higher in Group 1Y than in Group 2Y after 7 days (P < 0.05). Wound healing resistance at 21 days was higher than at 7 days in all groups (P < 0.05). Late wound healing resistance was not different between young and adult rats. It is concluded that bilateral orchiectomy diminished the wound healing resistance only in young animals at the 7th post‐operative day.     

Effect of Panax ginseng extract on the activity of diabetic fibroblasts in vitro

Numerous studies have demonstrated the various medicinal properties of Panax ginseng, including angiogenic, immuno‐stimulating, antimicrobial, and anti‐inflammatory activities, which can be helpful in chronic wound healing. However, a direct role for P. ginseng in chronic wound healing has not been demonstrated. The present study was designed to evaluate the effects of P. ginseng extract on diabetic fibroblasts in vitro. Human diabetic fibroblasts were cultured in the presence of Ginsenoside Rb1 (G‐Rb1), the active component in P. ginseng (10 ng/mL), and untreated diabetic fibroblasts were used as controls. Cell proliferation, collagen synthesis, the production of various growth factors (basic fibroblast growth factor [bFGF]; vascular endothelial growth factor [VEGF]; and transforming growth factor‐β1 [TGF‐β1]), and the synthesis of matrix metalloproteinase 1 (MMP‐1) and tissue inhibitor of metalloproteinases 1 (TIMP‐1) were compared using enzyme‐linked immunosorbent assay and immunofluorescence staining. Compared with the control group, G‐Rb1‐treated fibroblasts showed significantly (P < 0.05) higher levels of cell proliferation, collagen synthesis, VEGF, TGF‐β1, and TIMP‐1. However, no significant differences in bFGF and MMP‐1 levels were observed between the two groups. These results suggest that P. ginseng treatment may stimulate the wound‐healing activity of diabetic fibroblasts in vitro.     

Efficacy of Jasminum grandiflorum L. leaf extract on dermal wound healing in rats

Wound healing is a fundamental response to tissue injury and natural products accelerate the healing process. Here, we have explored the efficacy of topical administration of an ointment, prepared by methanolic extract of Jasminum grandiflorum L. (Oleaceae) leaves, on cutaneous wound healing in rats. The topical application of the Jasminum ointment on full thickness excision wounds accelerated the healing process. Tissue growth and collagen synthesis were significantly higher determined by total hydroxyl proline, hexosamine, protein and DNA content. The response was concentration‐ and time‐dependent, when observed on days 4, 8 and 12 after wound creation. The rate of wound healing was faster as determined by wound contraction, tensile strength and other histopathological changes. In addition, this ointment also raised the activity of superoxide dismutase (SOD) and catalase (CAT) with high GSH content and low lipid peroxidation products in wound tissue. Thus, it could be suggested that the ointment from the methanolic extract of J. grandiflorum leaf improves the rate of wound healing by enhancing the rate of collagen synthesis and also by improving the antioxidant status in the newly synthesised healing wound tissue.     

The combined effect of recombinant human epidermal growth factor and erythropoietin on full‐thickness wound healing in diabetic rat model

Diabetic wound is a chronic wound in which normal process of wound healing is interrupted. Lack of blood supply, infection and lack of functional growth factors are assumed as some of the conditions that lead to non‐healing environment. Epidermal growth factor (EGF) acts primarily to stimulate epithelial cell growth across wound. Erythropoietin (EPO) is a haematopoietic factor, which stimulates the production, differentiation and maturation of erythroid precursor cells. This study hypothesised combining these two factors, non‐healing process of diabetic wound will be compensated and eventually lead to acceleration of wound healing compared with single growth factor treatment. A total of 30 diabetic Sprague–Dawley rats were divided into three treatment groups (single treatment of rh‐EPO or rh‐EGF or combined treatment on a full‐thickness skin wound). To assess the wound healing effects of the components, the wound size and the healing time were measured in each treatment groups. The skin histology was examined by light microscopy and immunohistochemical analysis of proliferating markers was performed. The combined treatment with rh‐EPO and rh‐EGF improved full‐thickness wound significantly (P < 0·05) accelerating 50% healing time with higher expression of Ki‐67 compared with single growth factor‐treated groups. The combined treatment failed to accelerate the total healing time when compared with single growth factor treatments. However, the significant improvement were found in wound size reduction in the combined treatment group on day 4 against single growth factor‐treated groups (P < 0·05). This study demonstrated that the combined treatment of rh‐EPO and rh‐EGF improved the wound healing possibly through a synergistic action of each growth factor. This application provides further insight into combined growth factor therapy on non‐healing diabetic wounds.     

Evaluation of wound healing activity of ferulic acid in diabetic rats

In diabetic patients, there is impairment in angiogenesis, neovascularisation and failure in matrix metalloproteineases (MMPs), keratinocyte and fibroblast functions, which affects wound healing mechanism. Hence, diabetic patients are more prone to infections and ulcers, which finally result in gangrene. Ferulic acid (FA) is a natural antioxidant found in fruits and vegetables, such as tomatoes, rice bran and sweet corn. In this study, wound healing activity of FA was evaluated in streptozotocin‐induced diabetic rats using excision wound model. FA‐treated wounds were found to epithelise faster as compared with diabetic wound control group. The hydroxyproline and hexosamine content increased significantly when compared with diabetic wound control. FA effectively inhibited the lipid peroxidation and elevated the catalase, superoxide dismutase, glutathione and nitric oxide levels along with the increase in the serum zinc and copper levels probably aiding the wound healing process. Hence, the results indicate that FA significantly promotes wound healing in diabetic rats.     

Stromal vascular fraction improves deep partial thickness burn wound healing

ObjectiveThe practice of early burn wound excision and wound closure by immediate autologous skin or skin substitutes is the preferred treatment in extensive deep partial and full-thickness burns. To date there is no proven definite medical treatment to decrease burn wound size and accelerate burn wound healing in modern clinical practice. Stromal vascular fraction is an autologous mixture that has multiple proven beneficial effects on different kinds of wounds. In our study, we investigated the effects of stromal vascular fraction on deep partial-thickness burn wound healing.MethodsIn this study, 20 Wistar albino rats were used. Inguinal adipose tissue of the rats was surgically removed and stromal vascular fraction was isolated. Thereafter, deep second-degree burns were performed on the back of the rats by hot water. The rats were divided into two groups in a randomized fashion. The therapy group received stromal vascular fraction, whereas the control group received only physiologic serum by intradermal injection. Assessment of the burn wound healing between the groups was carried out by histopathologic and immuno-histochemical data.ResultsStromal vascular fraction increased vascular endothelial growth factor, proliferating cell nuclear antigen index, and reduced inflammation of the burn wound. Furthermore, vascularization and fibroblastic activity were achieved earlier and observed to be at higher levels in the stromal vascular fraction group.ConclusionsStromal vascular fraction improves burn wound healing by increasing cell proliferation and vascularization, reducing inflammation, and increasing fibroblastic activity.     

The analgesic hybrid of dermorphin/substance P and analog of enkephalin improve wound healing in streptozotocin‐induced diabetic rats

The purpose of this study was to investigate the effect of the peptide analgesic hybrid compounds: AWL3106 analog of dermorphin and substance P (7‐11), and biphalin enkephalin analog on wound healing in streptozotocin‐induced diabetic rats. The diabetes was induced in 6–7 week‐old male Wistar rats by intraperitoneal injection of streptozotocin. After 70 days, the wounds were created on the back of the rats and then, once a day for 21 days, the dressing containing lanolin ointment, 10% of keratin scaffolds, and 1 mM of AWL3106 or biphalin was applied. The wounds histology were analyzed by hematoxylin and eosin staining. The orientation and organization of collagen was analyzed by Masson's trichome staining. The number of macrophages, blood vessels, and fibroblasts were visualized by CD68, CD34, and vimentin immunoreactivity, respectively. Our results demonstrated that the wound area of AWL3106‐ and biphalin‐treated groups was greatly reduced (up to 47% on the 7 day) in comparison with untreated diabetic groups. The immunohistochemical staining of macrophages demonstrated that AWL3106 and biphalin accelerated inflammatory progression and subsequently decreased persistent inflammation. The histological analysis showed that the structure of tissue in the groups under the study was very similar to the one of wound tissue in N‐DM group. The H&E and Masson's trichome staining demonstrated that the orientation and organization of collagen as well as the number and shape of blood vessels were better in 3106‐ and BIF‐treated group than in DM group. In conclusion, the obtained data suggested that our hybrid peptides enhanced wound healing, particularly by accelerating the inflammatory phase and promoted the wound closure.     

The Effects of Resveratrol on the Healing of Left Colonic Anastomosis

Introduction: Resveratrol (RSV) is a natural polyphenolic compound found in grape skins and the red wine which improves histological reorganization of the regenerating tissue in dermal wound healing. Since anastomotic healing possesses paramount importance to prevent complications in colorectal surgery, the present study is aimed to evaluate the effect of RSV on the healing of experimental left colonic anastomoses. Methods: Thirty-two male Wistar albino rats were randomized into two groups and subjected to colonic anastomosis. The study group was treated with RSV and the control group received tap water instead. The rats were sacrificed 3 and 7 days postoperatively. Wound complications, intra-abdominal abscesses, and anastomotic leaks and stenosis were recorded. Four types of assessment were performed: bursting pressure, hydroxyproline (OHP) content, histopathology, and biochemical analysis. Results: Compared to the control group, the RSV-treated rats displayed a higher bursting pressure (p <. 001) and anastomotic OHP content (p <. 05)]. RSV treatment leads to significant increase in PON activity at both time points and decrease in malondialdehyde levels on postoperative day 3 (p <. 001). Histopathological analysis revealed that RSV administration leads to a better anastomotic healing in terms of mucosal ischemia, neovascularization, reepithelialization, fibroblast, and lymphocyte infiltration. Conclusion: The study results suggest that exogenous RSV administration exerts a positive effect on experimental colonic wound healing in the rat. Although the precise cellular mechanisms by which RSV enhances anastomotic wound healing is not clear, stimulation of neovascularization, generation of collagen synthesis, inhibition of overinflammation, and restriction of oxidative injury seems to be of paramount importance.     

复黄生肌愈创油膏对大鼠糖尿病创面中Ⅰ型和Ⅲ型胶原mRNA表达的动态影响

目的：动态观察复黄生肌愈创油膏对大鼠糖尿病创面新生肉芽组织中Ⅰ型和Ⅲ型胶原mRNA表达的动态影响。方法：36只雄性Wistar大鼠随机分为创面对照组、模型组、复黄膏组。采用荧光定量PCR技术,观察不同时段创面新生肉芽组织中Ⅰ型和Ⅲ型胶原mRNA表达的变化。结果：创面修复第11d,Ⅰ型胶原mRNA表达复黄膏组明显低于创面对照组（P〈0.05）,但和模型组比较无统计学差异;Ⅲ型胶原mRNA表达复黄膏组明显高于模型组（P〈0.05）,和创面对照组比较差异无统计学意义。结论：复黄生肌愈创油膏通过促进难愈性创面Ⅰ、Ⅲ型胶原增殖和平衡,从而起到促进创面愈合的作用。     

The Right Method for Midline Laparotomy: What is the Best Choice for Wound Healing ?

Background: The techniques used for midline laparotomy affect healing in surgical wounds, but the relationship between cold scalpel and haemostatic methods (harmonic scalpel, diathermy) regarding wound healing remains unclear. There are also limited studies concerning the effects of harmonic scalpel on abdominal fascia. This study was aimed at comparing myofascial wound healing following laparotomy incision on fascia by cold scalpel (CS), harmonic scalpel (HS), and diathermy in terms of hydroxyproline content, inflammatory changes and tensile strength. Materials and methods: Twenty-seven male Wistar albino rats underwent midline laparotomy either with cold scalpel (CS), harmonic scalpel (HS) or diathermy. Fascia incisions were closed with continuous 4/0 polypropylene and skin incisions were closed with interrupted 4/0 polypropylene stitches. On the 7^th postoperative day, the abdominal walls of the rats were tested for tensile strength. In addition, each abdominal fascia was evaluated for inflammation scores and hydroxyproline levels.

Results: HS caused less inflammation and necrosis in abdominal fascia compared to the diathermy group (p < 0.01 and p < 0.05, respectively), whereas the CS group showed no difference in inflammation scores, but had significantly lower necrosis scores than the HS and diathermy groups (p < 0.05 and p < 0.001, respectively). Hydroxyproline content of the fascia did not differ among groups, while the tensile strength of the wound was obviously higher in the CS group (p < 0.001).

Conclusion: HS causes less inflammatory reaction and necrosis than diathermy, but more necrosis than CS. Fascia incisions with CS gains tensile strength faster than in other groups. HS appears to cause less tissue injury than diathermy and also has comparable results for wound healing. Further clinical studies on the impact of HS in fascia incisions are needed.