Differential Effect of Electroacupuncture on Inflammatory Adipokines in Two Rat Models of Obesity.

Chronic inflammation is known to be associated with visceral obesity and insulin resistance which are characterized by altered levels of production of pro- and anti-inflammatory adipokines. The dysregulation of the production of inflammatory adipokines and their functions in obese individuals leads to a state of chronic low-grade inflammation and may promote obesity-linked metabolic disorders and cardiovascular diseases such as insulin resistance, metabolic syndrome, and atherosclerosis. Electroacupuncture (EA) was tested to see if there was a difference in its effect on pro- and anti-inflammatory adipokine levels in the blood serum and the white adipose tissue of obese Zucker fatty rats and high-fat diet-induced obese Long Evans rats. In the two rat models of obesity, on Day 12 of treatment, repeated applications of EA were seen to have had a significant differential effect for serum tumor necrosis factor-α, adiponectin, the adiponectin:leptin ratio, and blood glucose. For the adipose tissue, there was a differential effect for adiponectin that was on the borderline of significance. To explore these changes further and how they might affect insulin resistance would require a modification to the research design to use larger group sizes for the two models or to give a greater number of EA treatments.

Treatment of insulin resistance by acupuncture: a review of human and animal studies.

BACKGROUND: Numerous experimental studies have demonstrated that acupuncture can correct various metabolic disorders such as hyperglycaemia, overweight, hyperphagia, hyperlipidaemia, inflammation, altered activity of the sympathetic nervous system, and insulin signalling defects, all of which contribute to the development of insulin resistance. OBJECTIVE: To review human and animal studies investigating acupuncture as a treatment for insulin resistance, and to evaluate its potential to increase insulin sensitivity. METHODS: PubMed was searched for relevant articles published between January 2008 and October 2015. Search terms used were 'acupuncture', 'insulin resistance', 'insulin sensitivity', and 'blood glucose'. Additional secondary sources of information included reference lists from retrieved papers and pertinent papers identified by hand searches of relevant journals not found in the database. RESULTS: In total, 31 articles were included in this review and comprised studies of the following insulin resistant conditions: obesity (n=9); diabetes mellitus (n=12); polycystic ovarian syndrome (n=7); skeletal muscle atrophy (n=1); ischaemic heart disease (n=1); and fatty liver disease (n=1). Of these articles, seven were human trials and 24 animal experiments. Collectively, the studies suggest that electroacupuncture (EA) at low intensity and low frequency can reduce insulin resistance and increase insulin sensitivity in a range of different insulin-resistant conditions. CONCLUSIONS: EA, used alone or in combination with other therapies, such as Chinese herbs or diet-exercise interventions, has the potential to be an effective treatment for insulin resistance. Additional controlled clinical studies of acupuncture are needed in subjects with diabetes mellitus, ischaemic heart disease, muscle atrophy, and fatty liver disease.

Effects of Electroacupuncture on Pro-/Anti-inflammatory Adipokines in Serum and Adipose Tissue in Lean and Diet-induced Obese Rats.

The effects of electroacupuncture (EA) on pro-/anti-inflammatory cytokines and blood glucose (BG) in lean and obese Long Evans rats were investigated. Group 1 and Group 3 had five lean and seven obese rats, respectively, and received EA at the Zhongwan/Guanyuan acupoints on Day 1, Day 3, Day 5, Day 8, Day 10, and Day 12. Group 2 and Group 4, with five lean and seven obese rats, respectively, did not undergo EA. After induction of anesthesia, BG was measured at 10 minutes and 20 minutes. EA was applied for 30 minutes, and BG was measured again. At the end of the study, blood and white adipose tissue were collected. Analyses showed that for all groups, the mean BG at 20 minutes (baseline) and 50 minutes were significantly greater on Day 1 than on any other day. Compared with Group 2, the baseline BG in Week 1 for Group 1 was significantly lower, but Groups 3 and 4 showed no difference. Group 1 had significantly higher serum interleukin-10 and tumor necrosis factor-α than Group 2, while Group 3's serum leptin was greater than Group 4's. White adipose tissue interleukin-10 and adiponectin:leptin ratio were higher for Group 1 than Group 2. EA affected no significant differences in any other components measured for lean and obese animals.

Effect of Electroacupuncture on Inflammation in the Obese Zucker Fatty Rat Model of Metabolic Syndrome.

Chronic inflammation is known to be associated with visceral obesity and insulin resistance and is characterized by altered levels of production of adipokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, leptin, and adiponectin. Metabolic syndrome (MetS) is a major and escalating public health and clinical challenge worldwide, and patients with MetS have an increased risk of developing cardiovascular disease and type 2 diabetes mellitus. Electroacupuncture (EA) was tested as a means of decreasing inflammation in genetically obese Zucker fatty rats, which serve as a model of MetS. Repeated application of EA at the Zhongwan/Guanyuan acupoints decreased serum TNF-α, but produced no significant alterations in serum leptin, adiponectin, or IL-10. EA had no significant effect on the levels of these four adipokines in white adipose tissue. These findings are consistent with the supposition that EA inhibits proliferation and/or infiltration of macrophages into the adipose tissue of obese rats and stimulates the release of IL-10 from the decreased numbers of macrophages present in adipose tissue. Compared with the control animals, no significant change in body weight occurred. The blood glucose (BG) level over a 30-minute interval in Week 2 was relatively the same as that in Week 1, suggesting that EA treatment does not increase the likelihood of developing hyperglycemia.

Repeated electroacupuncture in obese Zucker diabetic fatty rats: adiponectin and leptin in serum and adipose tissue.

Fasted, male, obese, Zucker, diabetic fatty rats aged 10-16 weeks were anesthetized with 1% halothane in nitrous oxide-oxygen (3:1) on alternate weekdays over 2 weeks. Group 1 (n = 4) did not receive electroacupuncture (controls); Group 2 (n = 4) received electroacupuncture using the Zhongwan and the Guanyuan acupoints; Group 3 (n = 4) received electroacupuncture using the bilateral Zusanli acupoints; Group 4 (n = 6) received neither halothane in nitrous oxide:oxygen nor electroacupuncture. At the end of study, animals were injected with sodium pentobarbitone (60 mg/mL, i.p.), and blood and white adipose tissue were collected. Analysis of variance and Duncan's tests showed that the mean leptin in serum was significantly lower and the adiponectin:leptin ratio was significantly higher in Group 2 than in Group 1 (p < 0.05); for Group 4, the serum leptin was significantly higher than it was for Groups 1-3 (p < 0.05), and the adiponectin:leptin ratio was significantly lower than it was for Group 2 (p < 0.05). Similar changes occurred for the leptin levels in the pelvic adipose tissue. In addition, for Group 2, the mean serum insulin: glucose ratio was significantly higher than it was for Group 1 (p < 0.05); for Group 4 the mean serum insulin and insulin: glucose ratio were significantly higher than they were for Groups 1 and 3 (p < 0.05), but not Group 2 (p > 0.05). No significant differences in the serum or the adipose-tissue measurements between Groups 1 and 3 were observed (p > 0.05).

Repeated electroacupuncture: an effective treatment for hyperglycemia in a rat model.

The effect of electroacupuncture (EA) in lowering blood glucose (BG) in eight fasted male obese Zucker diabetic rats aged 21-24 weeks was investigated. Group 1 (n = 4) received no EA and Group 2 (n = 4) received EA at the Zhongwan and Guanyuan acupoints on Day 1, Day 3, Day 6, Day 8, and Day 10. The BG level of the rats was measured at 10 minutes and 20 minutes after their nose had been inserted into the nose cone of an anesthetic apparatus; then, EA was applied for 30 minutes, and BG was measured again. At the end of the study, the animals were injected with sodium pentobarbitone (60 mg/mL, intraperitoneally), and blood and white adipose tissue were collected. On statistical analysis, Group 2 showed a significant decrease in mean BG at 20 minutes (baseline) and 50 minutes on Day 8 and Day 10 compared with Day 1 and Day 3, but such a decrease was not observed in Group 1. For Group 2, the baseline BG and the change in BG over 30 minutes were significantly lower on Day 8 and Day 10 compared with Day 1, Day 3, and Day 6, but not for Group 1. No significant differences were noted between the groups in serum insulin, glucose, insulin-to-glucose ratio, adiponectin, leptin, adiponectin-to-leptin ratio, and white adipose tissue.

Defining a therapeutic window for laser irradiation (810 nm) applied to the inguinal region to ameliorate diabetes in diabetic mice.

OBJECTIVE: The purpose of this study was to determine a therapeutic window of antidiabetic effect by laser irradiating the left inguinal region of diabetic mice (810 nm 20.4 and 40.8 J/cm(2)) for 7 days. BACKGROUND DATA: Irradiation of 810 nm 10.2 J/cm(2) to the left inguinal region of diabetic mice for 7 days significantly decreased blood plasma fructosamine compared with nonirradiated controls. METHODS: Forty-seven diabetic mice were used. Body weight and water intake of the mice were measured daily for 7 days prior to start of treatment (day 0). Mice were irradiated on the left inguinal region with 810 nm laser 20.4 J/cm(2) (n=15) or 40.8 J/cm(2) (n=15) for 7 days, or were not irradiated (control, n=17). Body weight and water intake were measured to day 7. On day 7, mice were fasted for 5 h, anesthetized with sodium pentobarbitone (i.p.), and blood plasma was collected. The blood plasma was assayed for glucose and fructosamine. RESULTS: Water intake was significantly increased on day 7 compared with day 0 for diabetic mice receiving laser treatment. Blood plasma glucose levels on day 7 for diabetic mice irradiated 20.4 and 40.8 J/cm(2) were not significantly different than for nonirradiated controls. The blood plasma fructosamine level of diabetic mice irradiated with 20.4 J/cm(2) was significantly lower than for nonirradiated controls, whereas that for diabetic mice irradiated with 40.8 J/cm(2) was not significantly different than for nonirradiated controls. CONCLUSIONS: Irradiation (810 nm laser 10.2-20.4 J/cm(2)) to the left inguinal region of diabetic mice for 7 days has the potential to ameliorate diabetes, as is shown by decreased blood plasma fructosamine.

Repeated application of electroacupuncture ameliorates hyperglycemia in obese Zucker diabetic fatty rats.

Electroacupuncture (EA) was investigated for lowering the blood glucose (BG) in fasting male obese Zucker fatty diabetic (ZDF) rats aged 10-17 weeks. Anesthesia provided satisfactory chemical restraint to enable repeated EA. Animals in Groups 1, 2 and 3 were anesthetized on Days 1, 3, 5, 8, 10 and 12. Group 1 (n = 4) received no EA (controls), Group 2 (n = 4) EA at Zhongwan and Guanyuan acupoints, and Group 3 (n = 4) EA at both Zusanli acupoints. BG was measured at 10 and 20 minutes, and EA was applied for 30 minutes, after which BG was measured again. Group 2 had a significantly lower baseline BG at 20 minutes on Days 5, 8 and 12 and significantly less change in BG over 30 minutes on Days 3 and 5 than Group 1 (p < 0.05). Group 3 showed a significant decrease in the mean baseline BG compared to Group 1 in Week 1 (p < 0.05). Thus, repeated EA using Zhongwan and Guanyuan acupoints was effective in lowering the baseline BG and modulating the change in the BG in anesthetized animals.

Testing infrared laser phototherapy (810 nm) to ameliorate diabetes: irradiation on body parts of diabetic mice.

BACKGROUND AND OBJECTIVES: Irradiation of left flank of genetic diabetic mice with 660 nm wavelength laser, 100 mW, 20 seconds/day for 7 days did not significantly alter blood plasma glucose compared to nonirradiated controls. Infrared light would provide for a greater amount of photoenergy penetrating the skin and muscle. Genetic diabetic mice were irradiated with 810 nm wavelength laser to test for antidiabetic effect. MATERIALS AND METHODS: Sixty-five diabetic mice were used. Body weight and water intake of mice were measured daily for 7 days prior to start of treatment (Day 0). Mice were irradiated with 810 nm wavelength laser, 50 mW, 40 seconds/day, 7 days on left flank (n = 11), mid-upper abdomen (n = 14), or left inguinal region (n = 14); some mice were not irradiated (control, n = 26). Body weight and water intake of mice were measured to Day 7. On Day 7, mice were fasted for 4 hours, anesthetized with sodium pentobarbitone (s.c.) and blood collected by cardiac puncture into EDTA-treated tubes. Blood plasma was assayed for glucose and fructosamine. Blood was collected and assayed from nonirradiated nondiabetic mice (n = 12). RESULTS: On Day 7 body weight was significantly lower and water intake significantly higher compared to Day 0 for diabetic mice irradiated on left flank (40.7 ± 0.5 vs. 42.2 ± 0.4 g, 28.2 ± 1.5 vs. 23.4 ± 1.5 g, respectively); there was no significant change for diabetic mice irradiated on mid-upper abdomen or left inguinal region and also for nonirradiated diabetic mice. On Day 7 blood plasma glucose levels for irradiated diabetic mice were not significantly different to nonirradiated diabetic mice. Blood plasma fructosamine level of diabetic mice irradiated on left inguinal region was significantly lower than for nonirradiated diabetic mice (312 ± 6 vs. 377 ± 15 µmol/L); for diabetic mice irradiated on left flank or mid-upper abdomen (362 ± 22, 357 ± 19 µmol/L) it was not significantly different to nonirradiated diabetic mice. CONCLUSION: Irradiation of left inguinal region in diabetic mice with 810 nm laser has potential to ameliorate diabetes as shown by decreased blood plasma fructosamine.

Gene expression and release of growth factors during delayed wound healing: a review of studies in diabetic animals and possible combined laser phototherapy and growth factor treatment to enhance healing.

OBJECTIVE: The purposes of this study were: to review studies of growth factors in cutaneous wounds of animals with diabetes to identify those factors with altered gene expression and content compared with nondiabetic animals; and to explore which deficiencies of growth factors in diabetic wounds may or may not be improved by laser irradiation. BACKGROUND DATA: Wound healing is compromised in diabetes. Decreased production and/or increased destruction of growth factors may be responsible. Laser irradiation can increase the gene expression and release of certain growth factors by cells. METHODS: Research articles investigating growth factor expression in wounds of nondiabetic and diabetic mice and rats published through September 2011 were retrieved from library sources, PubMed databases, reference lists of articles, and searches of relevant journals. RESULTS: Vascular endothelial growth factor (VEGF), placental growth factor (PlGF), keratinocyte growth factor (KGF), fibroblast growth factor 1 (FGF-1), FGF-2, insulin-like growth factor 1 (IGF-1), IGF-2, transforming growth factor beta (TGF-ß), and nerve growth factor (NGF) had decreased gene expression and content in early phases of healing for diabetic wounds. Gene expression of KGF, IGF-1, and IGF-2 was delayed, whereas that of FGF-1 and FGF-2 occurred earlier, in diabetic compared with nondiabetic wounds. CONCLUSIONS: Growth factor administration combined with laser irradiation may provide an effective therapy to maximize healing of diabetic wounds.

Electroacupuncture for control of blood glucose in diabetes: literature review.

Electrical stimulation at acupuncture points (acupoints) has been investigated for its utility in lowering blood glucose in hyperglycemic humans and animal models. Only two studies were found using electroacupuncture in human subjects, and in both of these, the participants were normal (nondiabetic) and electrical stimulation was carried out at several acupoints. It had a hypoglycemic effect in obese women with calorific restriction diet using electrical stimulation of 2 Hz for 30 minutes/day for 20 days, but no change occurred in blood glucose of fasted patients in the other study using 1 Hz for 15 minutes. Fourteen animal studies were found, of which, 11 were performed in diabetic and normal rats. A hypoglycemic effect was observed in fasted type 1 diabetic rats using the Zusanli (ST36) leg acupoint with electrical stimulation of 15 Hz for 30 minutes and 60 minutes. In fasted type 2 diabetic rats, blood glucose was lowered using the Zusanli acupoint with electrical stimulation parameters of 15 Hz and 10 mA for 30 minutes. Also, using the Zhongwan (CV12) abdomen acupoint with electrical stimulation parameters of 15 Hz and 10 mA for 90 minutes had a hypoglycemic effect in fasted type 2 diabetic rats. In fasted normal rats, electrical stimulation of 2 Hz or 15 Hz for 30 minutes at the Zusanli or Zhongwan acupoint caused a decrease in blood glucose. Future studies are required in fasted diabetic rats to determine the effect of electroacupuncture on blood levels of insulin, lipids, fatty acids and ß-endorphin, and blood flow and nerve conduction velocity. Studies with fasted normal and diabetic human subjects treated by electroacupuncture are warranted using data from animal experiments to inform such studies.

Photodynamic modulation of wound healing: a review of human and animal studies.

OBJECTIVE: The purpose of this study was to review studies of photodynamic therapy (PDT) on wound healing and cells in vitro, to assess the effects of such therapy. BACKGROUND DATA: PDT is used to treat tumors. When activated by light of a specific wavelength, the photosensitizer produces reactive oxygen species (ROS) that kill tumor cells. Low levels of ROS may induce cellular proliferation. METHODS: Research articles investigating PDT on wound healing and cells in vitro published up to August 2010 were retrieved from library sources, PubMed and Medline databases, reference lists of articles, and searches of relevant journals. RESULTS: The studies indicated that use of various photosensitizers combined with laser irradiation led to improved wound outcomes. For most in vitro studies, there was a decrease in cell growth or viability. CONCLUSIONS: PDT improved healing outcomes in several animal wound models, but mainly had an inhibitory effect on cells in vitro. These findings strongly support PDT for wound healing.

Laser photostimulation (660 nm) of wound healing in diabetic mice is not brought about by ameliorating diabetes.

BACKGROUND AND OBJECTIVES: We have used a 660-nm laser diode in genetic diabetic mice to stimulate the healing of wounds covered with a Tegaderm HP dressing that causes a retardation of contraction (splinted wounds). It is possible that the stimulation of healing could be due to possible diabetes-modifying properties of laser light. This has been examined by using the 660 nm laser to irradiate non-wounded diabetic mice with the same dose and at same location as for wounded diabetic mice. MATERIALS AND METHODS: Twenty-two diabetic mice were used and divided into two equal groups. Body weight and water intake of mice were measured daily for 7 days prior to the start of treatment (Day 0). The left flank of mice in the experimental group was irradiated with 660 nm laser, 100 mW, 20 seconds/day, 7 days; for mice in the control group, the left flank was sham-treated with the laser power supply not switched on. Body weight and water intake of mice were measured to Day 14. On Day 14, the mice were fasted for 4 hours, anaesthetized with sodium pentobarbitone (i.p.) and blood collected by cardiac puncture into heparinized tubes. The plasma was assayed for glucose and glycated hemoglobin A1c. RESULTS: There were no significant differences in body weight and water intake over 22 days between mice in the experimental group and control group. On day 14, the mean blood plasma glucose level was not significantly different between the two groups; glycated hemoglobin A1c was not detected in the samples. CONCLUSION: Irradiation of the left flank in diabetic mice with 660 nm laser system does not have a significant hypoglycemic effect, and the laser-stimulated healing of wounds in diabetic mice is due to cellular and biochemical changes in the immediate wound environment.

Laser photobiomodulation of gene expression and release of growth factors and cytokines from cells in culture: a review of human and animal studies.

AIM: The aim of this paper was to review experimental studies of laser irradiation of human and animal cells in culture to assess the photobiomodulatory effects of such irradiation on gene expression and release of growth factors and CYTOKINES. BACKGROUND: Previous studies have reported that the release of certain growth factors and cytokines by various types of cells can be modulated by laser irradiation. A review of recent studies may provide further insight into the clinical effects brought about by laser irradiation of cells and tissues, including changes in inflammation and cellular proliferation. METHODS: A systematic review was completed of original research papers investigating the effects of laser phototherapy on gene expression and release of these mediators from human and animal cells in culture (January 2002 to September 2009). Relevant papers were retrieved primarily from PubMed and Medline databases. The search terms were "growth factors", "cytokines", "laser therapy", "laser irradiation", "laser phototherapy," and "phototherapy". RESULTS: A total of 17 relevant papers were included in the review, comprising studies on a variety of cell types. Considerable variation occurred in research design, methodology, and irradiation parameters employed, limiting comparison of research findings between studies. Results demonstrated that laser irradiation at green, red, or infrared wavelengths at a range of dosage parameters can cause significant changes in the cellular gene expression and release of these mediators, and that such effects depend upon wavelength and radiant exposure. CONCLUSION: Findings from the reviewed studies clearly demonstrate the ability of laser irradiation to modulate gene expression and the release of growth factors and cytokines from cells in culture. Further work is indicated at the clinical level to elucidate the putative clinical relevance of these cellular-level effects.

Laser photobiostimulation of wound healing: defining a dose response for splinted wounds in diabetic mice.

BACKGROUND AND OBJECTIVES: We have used a 660 nm, 80 mW laser diode in genetic diabetic mice to stimulate the healing of wounds covered with a Tegaderm HP dressing that causes a retardation of contraction (splinted wounds). The purpose of our study was to examine the effects of irradiating the wounds for different time intervals in order to determine a dose response relationship. MATERIALS AND METHODS: A circular excisional wound was made on the left flank of diabetic mice using a 5-mm skin punch, and covered with a Tegaderm HP dressing. Mice were allocated to four groups in which wounds were irradiated 660 nm, 80 mW for 0, 10, 20, or 40 seconds each day for 7 days. In total, 51 mice were used. Wounds were harvested on day 14 and the healing assessed from hematoxylin-eosin stained sections examined by light microscopy. RESULTS: The wounds were splinted in 40 of the mice, and splinting caused a retardation of healing. The findings for the four treatments showed that irradiation for 20 second/day for 7 days brought about the greatest extent of healing. The wounds healed mainly by re-epithelization and granulation tissue formation. This duration of irradiation represents an energy dose of 1.6 J per irradiation and, for an estimated area of irradiation of 32-43 mm², corresponds to an energy density of 3.7-5.0 J/cm². CONCLUSION: Irradiation with 660 nm, 80 mW at an energy density of 3.7-5.0 J/cm² each day for 7 days caused the maximal stimulation of healing in splinted wounds of diabetic mice.

Laser photobiomodulation of proliferation of cells in culture: a review of human and animal studies.

AIM: The aim of this article was to review experimental studies of laser irradiation of human and animal cells in culture to assess the photobiomodulatory effects of such irradiation. BACKGROUND: Previous studies have shown that various types of cells respond differently to laser irradiation, depending on irradiation parameters. Cellular outcomes measured or examined include cell numbers, cell viability, and ultrastructural features. A review of these studies may provide a further insight into the clinical effects brought about by laser light on cells and tissues, including laser effects in wound healing and repair of nerves and skeletal muscle after injury. METHODS: A systematic review was completed of original research articles investigating the effects of laser therapy on human and animal cells in culture (January 2002 to September 2009). Relevant articles were primarily sourced from PubMed and Medline by using EndNote X1, and from secondary searches. Search terms were "cell proliferation," "laser therapy," "laser irradiation," "laser phototherapy," and "phototherapy." RESULTS: In total, 46 relevant articles were included in the review, comprising work completed on a variety of cell types. Although results consistently demonstrated the potential of laser irradiation to affect cellular proliferation in a wavelength- and dosage-dependent manner, the relevance of other key irradiation parameters, such as irradiance, to such effects remained unclear. CONCLUSIONS: Findings from studies of cells in culture clearly demonstrate the ability of laser irradiation to modulate (typically stimulate) cellular proliferation. The relevance of some irradiation parameters remains occult and represents an important area for further research.

Testing photobiomodulatory effects of laser irradiation on wound healing: development of an improved model for dressing wounds in mice.

OBJECTIVE: To develop a suitable method for dressing skin wounds in BKS.Cg-m(+)/(+)Lepr(db) mice for subsequent use in laser irradiation of wounds. The healing of nonirradiated wounds (controls) was examined histologically to provide essential reference data. BACKGROUND DATA: Dressing excisional skin wounds in mice has many advantages. However, previous studies using dressings such as Tegaderm W or OpSite, with or without adhesives, have shown that this is not easily achieved. MATERIALS AND METHODS: In a pilot study, a full-thickness wound was made on the left flank in six diabetic and six nondiabetic mice, and five different methods were tried for dressing the wounds with Tegaderm HP to develop an optimized procedure. The optimized procedure was used in subsequent studies, with a total of 23 diabetic and 13 nondiabetic mice being controls for laser-irradiated mice. Measurements of healing outcomes from histologic sections of controls were statistically analyzed. RESULTS: The optimized procedure used Tegaderm HP with Cavilon and Fixomull Stretch strips for the first dressing, and with Mastisol for subsequent dressings. Wound closure by contraction was retarded in a large proportion of diabetic mice (approximately 80%) and a small proportion of nondiabetic mice. These wounds, described as "splinted," healed mainly by epithelial regeneration and granulation tissue formation. CONCLUSION: A simple, easy-to-perform procedure was developed for dressing wounds in diabetic and nondiabetic mice. It was found to cause splinting with wound healing mimicking that in human patients. This model is suitable for examining the effects of different therapies on wound healing, including lasers.