| Background:In recent years,in view of the large area of skin and soft tissue defects caused by trauma,besides the traditional free skin grafting,skin flap technology,tissue engineering,skin expansion,stem cell transplantation and other technologies,the application of skin stretching technology has gradually increased,and achieved good results.The principle of skin stretching is to utilize the mechanical creep properties of skin.However,skin stretching also has some limitations,such as limited stretching,ambiguous limit value of distraction closure in various parts of the human body,and skin edge necrosis after stretching.Among them,ischemic necrosis of the posterior skin margin?especially the distal skin of the limbs?is one of the biggest obstacles limiting the application of skin stretching in wounds.Papaverine is a classical non-specific vasodilator,which is often used to prevent vasospasm after skin flap and vascular surgery.At present,the effect of papaverine on wound healing after skin stretching has not been reported at home and abroad.The purpose of this study was to establish a full-thickness skin defect wound model of Bama swine forearm and to study whether papaverine could improve the healing rate of acute stretching wound closure by using hook-pin pull-rod skin distractor according to standardized process,and to further explore its related mechanism,so as to provide clinical treatment for acute stretching wound closure.Methods:1.Establishment of full-thickness skin defect of forearm in swine:three male Bama miniature swine with forelimbs of 6 cm×6 cm,6.5 cm×6.5 cm,7 cm×7 cm,7.5 cm×7.5 cm,8 cm×8cm square 1822kg full-thickness skin defect were established.Standardized stretching process:0.5 cm from the outer edge of the wound,the hook needle was punctured vertically,and a new type of stretching rod skin stretcher was assembled and fixed equally on both sides of the median longitudinal axis of the wound.Three groups of crochet needles were used for each wound margin,and 15 N force was used for stretching.The skin was stretched continuously for 4 minutes and the stretcher was loosened for 1 minute.The operation cycle was repeated for 6 cycles and 30 minutes.The wound was closed by stretch according to the standardized stretch procedure.2.Eight Bama swine were divided into two groups according to the random number method.Standard full-thickness skin defect wounds of 7 cm×7 cm were made in the middle forearm of each pig,and skin stretching devices were used to close the wounds in accordance with standardized procedures.There were 4 swine in both the control group and the experimental group.Animals in the experimental group were intramuscularly injected with papaverine hydrochloride at the dose of 1.5mg/kg one hour before surgery.The control group was injected with the same dose of normal saline.The wound was cleaned and dressings were changed daily.3.Clinical scoring of wound healing:On the 4th and 10th day postoperative,the wound healing was scored by the researcher who did not know the animal group beforehand,using the“Clinical scoring of wound healing standard”proposed by Freeman et al.4.At postoperative day 10,the suture was removed.The effective stretching ratio was calculated by the middle wound with the following ratio:initial width of midlevel wound-width of mid level wound dehiscence/mid-forearm circumference×100%in the middle wound.Dehiscence width of middle wound,distal wound and longitudinal wound,wound healing rate,unhealed area of wound,the healing rate of the wound were recorded.5.Skin microcirculation was measured by transcutaneous partial pressure of oxygen?TcPO2?.The wound was cleaned and dressings were changed daily.The percutaneous oxygen partial pressure?TcPO2?was compared Preoperative and postoperative.6.Microvessel density?MVD?of wound margin tissue preoperatively and postoperative day 10 was measured by HE staining and Weidner counting method.Hypoxia inducible factor-1??HIF-1??and vascular endothelial growth factor?VEGF?were detected by immunohistochemistry before and during operation,and four and ten days after operation.Image J image processing software was used to semi-quantitatively analyze the above two factors using integrated optical density?IOD?.Results:1.The acute closure of full-thickness skin defect wounds of 7 cm×7 cm in the middle Forearm of male Bama swine?1822 kg?and skin stretching devices were used to close the wounds in accordance with standardized procedures.But 6 cm×6 cm and 6.5 cm×6.5 cm wounds can be closed completely by stretching.No necrosis or dehiscence of wounds can be seen postoperative.7.5 cm×7.5 cm and 8 cm×8 cm wounds can not be closed by stretching.2.Clinical scoring of wound healing:There was no statistically significant difference in clinical scoring of wound healing between the two groups at 4 day after skin stretching?2.63±0.74 vs 2.13±0.35,P>0.05?,but better result was found at the 10th day?1.25±0.46 vs4.63±0.74,P<0.01?.3.In this study,the effective stretching ratio of the middle part of the wound in the experimental group?39.82±1.49?%was better than that of the control group?32.54±6.46?%,with significant difference between the two groups?P<0.01?,which was 7%higher in the experimental group.The width of the middle part of the wound in the experimental group?0.00±0.00?cm was shorter than that of the control group?1.26±1.19?cm,and the difference was statistically significant?P<0.01?.The width of the distal part of the wound in the experimental group?2.50±1.11?cm was shorter than that of the control group?3.65±1.52?cm,and the difference was statistically significant?P<0.05?.The length of the longitudinal wound in the experimental group?1.66±1.05?cm was shorter than that of the control group?4.51±2.13?cm,with significant differences.The unhealed area of the wound in the experimental group?2.18±1.07?cm2 was less than that of the control group?11.84±4.00?cm2,and the difference was statistically significant?P<0.01?.The wound healing rate in the experimental group?95.50±2.14?%was higher than that of the control group?76.00±8.09?%,and the difference was statistically significant?P<0.01?.Papaverine can improve wound healing rate by 19.50%and can promote the healing rate of acute wounds closed by skin stretching device.4.After the application of papaverine,there was no statistically significant difference in TcPO2 between the experimental group?55.09±5.44?mmHg and the control group?54.65±5.90?mmHg before skin stretching?P>0.05?,while statistically significant difference was found after stretching?22.71±3.30mmHg vs 16.35±3.42mmHg,P<0.05?.5.In the experimental group,there were?9.29±1.15?MVD preoperatively and?29.50±4.76?MVD at postoperative day 10,while in the control group,there were?8.50±1.30?MVD preoperatively and?21.08±3.40?MVD at postoperative day 10,which was significantly higher at postoperative day 10 than preoperatively in both groups?P<0.05?,and was higher in the experimental group than that in the control group?P<0.05?.The expression of hypoxia inducible factor-1?in wound margin tissues:IOD value of experimental group preoperatively?21.74±4.03?,2 cycles?22.12±5.18?,4 cycles?24.07±4.93?,6 cycles?20.17±4.02?,at postoperative day 4?49.99±6.99?,at postoperative day10?36.98±10.62?;IOD value of control group preoperatively?21.52±5.52?,2 cycles?23.17±4.02?;?25±4.15?,4 cycles?21.29±5.12?,6 cycles?22.95±4.44?,at postoperative day4?38.63±7.04?and at postoperative day 10?31.08±7.61?.In the control group,the expression of hypoxia inducible factor-1?at the postoperative day 4 was significantly higher than that preoperatively?P<0.05?,while in the experimental group,the expression of hypoxia inducible factor-1 at postoperative days 4 and 10 was significantly higher than that preoperatively?P<0.05?.The expression of hypoxia inducible factor-1?at postoperative days 4 in the experimental group increased significantly compared with the control group?P<0.05?.Conclusions:1.Acute mechanical stretching closure was performed on the 7 cm×7 cm acute wound of the middle forelimb of Bama swine,the skin viscoelasticity could be used to achieve closure during the operation,but the wound showed signs of necrosis and dehiscence.This study is a standardized full-thickness skin defect acute stretching closure model.2.Whole body application of papaverine can enhance the effective stretch ratio,wound healing rate,wound healing score and immediate postoperative TcPO2 after the acute distraction closure of full-thickness skin defects in swine.3.The mechanism of whole body application of papaverine in improving wound healing after acute distraction closure is to improve the hypoxia in the surrounding tissues and promote local capillary regeneration,which may promote the expression of HIF-1?and VEGF. |
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