| BackgroundWith the development of industrial civilization of human society and the increase of a variety of trauma, an aging population and diabetics, refractory wounds increasingly occur and gradually become a burden on a medical system. In addition, doctors frequently encounter various wounds after tumor operations and various secondary wounds after surgery. Over the years, wound researchers have conducted research on the occurrence mechanism of wound healing, experimental and clinical treatment of wounds and the like by using histopathological, pharmacological, tissue engineering and surgical means and have made achievements; however, due to lack of a proper animal wound model, diversity and complexity of clinical wounds, etc., no significant progress has been made in research on wound healing for quite a long time.Currently, the therapy of compress changing is commonly adopted for treatment of superficial wounds in clinical practice; but the therapy needs a long period of treatment time and has a poor curative effect, gauze is easily wetted by exudates, which leads to contamination and re-infection, and a dressing has to be frequently changed. For deep wounds or lacunas, a drainage tube is normally used for drainage; both active and passive drainage are realized in virtue of the end hole and finite side holes of the drainage tube, full contact between the drainage tube and a drainage chamber is hard to achieve, and thus, such drainage is point-like or multi-point drainage; moreover, the drainage tube is exposed out of the drainage chamber, which easily results in blockage of the drainage tube. For a severe wound with a large area of a complex tissue defect, a traditional approach is to carry out debridement on the wound surface, bandaging with a sterile dressing and repeated changing of the dressing on the wound and then to perform skin grafting or skin flap grafting to repair the closed wound surface and the tissue defect when inflammations are controlled, the wound surface is new and granulation grows well. The traditional approach has the following disadvantages:the wound undergoes substantial exudation, drainage is inadequate, exudates accumulate on the wound surface, granulation tissue grows slowly, and a long course of treatment is needed; moreover, due to difficulty, high requirements on equipment and personnel and complicated and time-consuming operation of skin flap grafting, badly wounded patients can barely bear skin flap grafting, and skin flap grafting even makes their wounds worse.Vacuum-assisted closure (VAC) is a new method for treatment of a variety of acute and chronic refractory wounds, has been widely used in various types of acute and chronic wound surfaces in departments like trauma surgery, orthopedics, general surgery and burn departments and has achieved good therapeutic results. VAC is recommended for adjuvant treatment of a variety of acute and chronic wounds, including pressure wounds, diabetic feet, leg wounds, surgical incisions, wounds occurred after tumor resection, burn wounds, infected wounds, necrotizing fasciitis, infectious sternal wounds, etc. It is proved that VAC is a simple, economical and purely physical therapy for promotion of wound healing and has the advantages of a fast wound healing speed, a low infection rate, a few dressing changes, etc.Artificial dermis has been extensively applied in clinical practice. Clinical and animal studies have confirmed that artificial dermis not only can help repair a variety of full-thickness skin defects but also exert a therapeutic effect on repair of wounds with exposed tendons and bones. Artificial dermis grafting is simple and efficient to operate and easy to popularize, presents a high surgical success rate and can effectively repair wounds and prevent the wounds from infection. Due to shorter operative time, no great influence is posed to the wound of a patient. As dermis-like tissue forms after a first-stage operation, a full-thickness graft-like skin graft can be formed after survival of an autologous split-thickness skin graft grafted in a second-stage operation. Compared with a flap, the full-thickness graft-like skin graft is not bloated and slightly contracts after the operations; normally, functions are not substantially influenced, and the majority of healed wounds need no further surgery. For a donor site, mild pigmentation occurs at the donor site since only a thin split-thickness skin graft is cut, scar proliferation does not occur, and the donor site of artificial dermis grafting has more remarkable advantages compared with the donor site of flap grafting.VAC and artificial dermis grafting are new treatment techniques for wounds in recent years and can be used for treatment of various acute and chronic wounds. Clinical wounds are often accompanied by infection of varied degrees. Is it possible to clear bacteria infecting wounds and control infection by using VAC so as to provide a good wound base for further artificial dermis grafting? Can VAC promote vascular collagenization of artificial dermis and improve the survival rate of grafted artificial dermis? Is it feasible to make full use of respective advantages of VAC and artificial dermis grafting and integrate VAC and artificial dermis grafting as a novel approach for treatment of wound surfaces? The paper is to discuss feasibility of combination of VAC and artificial dermis grafting in treatment of refractory wounds, to explore the probable mechanism of the combined therapy in promotion of wound healing at cellular and molecular levels and to provide a new treatment method for clinical refractory wounds and theoretical and practical basis for clinical application of the combined therapy.ObjectiveThe invention is to observe influence of VAC on the conditions of a wound base and formation of dermis-like tissue after artificial dermis grafting, to explore feasibility of application of combination of VAC and artificial dermis grafting in treatment of wounds, to provide theoretical and practical basis for further research on and clinical application of combined VAC and artificial dermis grafting, to apply the therapy of VAC combined with grafting of artificial dermis and autologous epidermis in repairing of clinical refractory wounds and to observe treatment effects of the therapy.Material and MethodsPart â… :Experimental studyAnimal experiment1:120SD rats in total. A circular wound with a diameter of3cm was made on the back of each of80SD rats, then Staphylococcus aureus was inoculated for preparation of models of infected wounds, and then the80SD rats were divided into an experimental group and a control group, each group consisting of40SD rats; for the experimental group, VAC surgery was conducted on the wounds of the rats and continuous suction was carried out under the condition of a negative pressure value of-120to-125mmHg, while for the control group, conventional wet compressing and dressing changing with saline gauze pieces were carried out on the wounds of the rats; bacterination of the wounds and conditions of wound exudates and granulation tissue growth before and after treatment were observed; the quantities of newborn granulation tissue were respectively measured in4days and in8days after treatment. Then the circular wound3cm in diameter was made on the back of each of another40SD rats, then Staphylococcus aureus was inoculated for preparation of models of infected wounds, and then the40SD rats were divided into an experimental group and a control group, each group consisting of20SD rats; for the experimental group, VAC surgery was conducted on the wounds of the rats and continuous suction was carried out under the condition of a negative pressure value of-120to-125mmHg, while for the control group, wet compressing and dressing changing with saline gauze pieces were adopted for the wounds of the rats; tissue specimens were taken for HE staining respectively in4days and in8days after treatment, the morphology of granulation tissue was observed, and bacteriological detection was carried out on the wounds before and after treatment.Animal experiments â…¡:The circular wound3cm in diameter was made on the back of each of40SD rats, then Staphylococcus aureus was inoculated for preparation of models of infected wounds, VAC surgery was conducted on the wounds of the rats, and continuous suction was carried out under the condition of a negative pressure value of-120to-125mmHg; after new growth of granulation tissue, artificial dermis was grafted, and then the40SD rats were divided into an experimental group and a control group, each group consisting of20SD rats; the wounds of the experimental group were subjected to continuous suction and treatment at the negative pressure value of-120to-125mmHg, while the wounds of the control group underwent conventional pressure bandaging and dressing changes with saline gauze pieces; generally, the process of vascular collagenization of artificial dermis was observed with naked eyes; and materials were drawn from the wounds immediately, in4days and in8days after artificial dermis grafting, respectively.1, counting of vascular endothelial cells (VEC) was realized on the basis of CD34immunohistochemical results;2, the method of Masson’s staining was employed for observation of the morphology of collagen fibers at the bottom of a graft bed and for counting of fibroblast cells;3, an immunohistochemical staining method was used for detecting expression of the Ki-67antigen of tissue specimens and for observing and counting proliferative cells;4, after tissue homogenization, the contents of a vascular endothelial growth factor (VEGF), a tumor necrosis factor-a (TNF-a) and interleukin-6(IL-6) in tissue of the wounds were detected by using the ELIS A method; and5, bacteriological detection was carried out on tissue.Part II:Clinical studyThe therapy of VAC combined with grafting of artificial dermis and autologous epidermis was conducted on23cases of patients with refractory wounds hospitalized in March,2012to September,2013for wound healing so as to evaluate clinical efficacy of the therapy on healing of refractory wounds.ResultsPart I:Experimental studyAnimal experiment I:1, VAC can promote new growth of granulation tissue. The quantities of newborn granulation tissue on the wounds changed along with the time changed (F=6.149, P=0.018), the effect existed in the time (F=377.603, P=0.000), and the effect existed between various groups (F=258.167,P=.000). In4days after treatment, the quantities of newborn granulation tissue on the wounds of the experimental group were2.4ml, while the quantities of newborn granulation tissue on the wounds of the control group were1.8ml; the growth rate of granulation of the experimental group was significantly higher than that of the control group (t=14.634,P=0.000).In8days after treatment, the quantities of newborn granulation tissue on the wounds of the experimental group were3.6m, while the quantities of newborn granulation tissue on the wounds of the control group were2.7ml; the growth rate of granulation of the experimental group was significantly higher than that of the control group (t=9.652, P=0.000)2, VAC can promote clearance of bacteria on infected wounds. The number of bacteria in the wounds changed along with the time changed (F=3247.263, P=0.000), the effect existed in the time (F=7260.152, P=0.000), and the effect existed between various groups(F=6016.198,P=0.000). In4days after treatment, the number of bacteria in the wounds of the experimental group significantly decreased compared with those of the control group, and the difference was statistically significant (t=-34.325, P=0.000); In8days after treatment, the number of bacteria in the wounds of the experimental group continuously decreased, being significantly lower than those of the control group (t=-109.083, P=0.000).Animal experiment â…¡:1, VAC can promote the process of vascular collagenization of artificial dermis. According to observation results, artificial dermis survived in8days after treatment and was lightly red; a surface silica gel membrane and a collagen sponge layer began to separate.2, The number of the collagen fibers at the bottom of the graft beds of the wounds of the experimental group substantially increased compared with that of the control group. The numbers of VEC in the wounds changed along with the time changed(F=1426.371,P=0.000), the effect existed in the time(F=3119.444,P=0.000), and the effect existed between various groups (F=2397.294, P=0.000). In4days after treatment at the bottom of the graft beds of the wounds of the experimental group, the numbers of VEC continuously increased, being significantly higher than those of the control group (t=14.666, P=0.000). In8days after treatment at the bottom of the graft beds of the wounds of the experimental group, the numbers of VEC continuously increased, being significantly higher than those of the control group (t=45.330, P=0.000). The numbers of fibroblast cells in the wounds changed along with the time changed (F=245.726, P=0.000), the effect existed in the time (F=1055.623, P=0.000), and the effect existed between various groups (F=406.302, P=0.000). In4days after treatment at the bottom of the graft beds of the wounds of the experimental group, the numbers of fibroblast cells continuously increased, being significantly higher than those of the control group (t=18.801,P=0.000). In8days after treatment at the bottom of the graft beds of the wounds of the experimental group, the numbers of fibroblast cells continuously increased, being significantly higher than those of the control group (t=21.509, P=0.000)3, The content of VEGF in the wounds changed along with the time changed (F=1222.907,P=0.000), the effect existed in the time (F=1782.206,P=0.000), and the effect existed between various groups (P=1232.433, P=0.000). In4days after treatment in the wounds of the experimental group, the content of VEGF continuously increased, being significantly higher than those of the control group (t=25.156, P=0.000). In8days after treatment in the wounds of the experimental group, the content of VEGF continuously increased, being significantly higher than those of the control group (t=58.821,P=0.000). The number of the proliferative cells in the wounds changed along with the time changed (F=1068.889, P=0.000), the effect existed in the time(F=1459.412,P=0.000), and the effect existed between various groups (F=2127.536, P=0.000). In4days after treatment at the bottom of the graft beds of the wounds of the experimental group, The number of the proliferative cells continuously increased, being significantly higher than those of the control group(t=35.509,P=0.000). In8days after treatment at the bottom of the graft beds of the wounds of the experimental group, The number of the proliferative cells continuously increased, being significantly higher than those of the control group (t=41.038, P=0.000)4, The contents of TNF-a in the wounds changed along with the time changed (F=14.479, P=0.000), the effect existed in the time (F=86.337, P=0.000), and the effect existed between various groups (F=24.706, P=0.000). In4days after treatment in the wounds of the experimental group, the contents of TNF-a continuously decreased, being significantly lower than those of the control group (t=-3.574, P=0.001). In8days after treatment in the wounds of the experimental group, the contents of TNF-a continuously decreased, being significantly lower than those of the control group (t=-6.054,P=0.000). The contents of IL-6in the wounds changed along with the time changed (F=15.924,P=0.000), the effect existed in the time (F=168.997,P=0.000), and the effect existed between various groups (F=15.247, P=0.000). In4days after treatment in the wounds of the experimental group, the contents of IL-6continuously decreased, being significantly lower than those of the control group (t=-4.322, P=0.000). In8days after treatment in the wounds of the experimental group, the contents of IL-6continuously decreased, being significantly lower than those of the control group (t=-4.940, P=0.000)5, The number of bacteria in the wounds changed along with the time changed (F=1707.123, P=0.000), the effect existed in the time (F=7229.979,P=0.000), and the effect existed between various groups(F=6175.497, P=0.000). In4days after treatment, the number of bacteria in the wounds of the experimental group significantly decreased compared with those of the control group, and the difference was statistically significant (t=-71.624, P=0.000); In8days after treatment, the number of bacteria in the wounds of the experimental group continuously decreased, being significantly lower than those of the control group (t=-95.499, P=0.000)Part â…¡:Clinical studySignificant treatment effects were achieved in clinical cases. The wounds were quickly cleaned, granulation tissue rapidly grew, so conditions were created for further artificial dermis grafting. The average length of hospital stay of the patients was36days. Negative pressure suction was carried out for14days on average for granulation tissue culture, and then artificial dermis grafting was conducted. For22cases (95.7%) of the wounds, grafting of artificial dermis and subsequent second-phase grafting of autologous epidermis were successful. The average time needed for survival of the artificial dermis was14days, and dissolution and necrosis of the artificial dermis did not occur. The rest case is a child with a perineal wound; the artificial dermis for the wound was removed because of infection, and then the wound was successfully healed by using myocutaneous flap surgery. All the donor sites were successfully epithelialized and healed, with average healing time being9days. Changing frequencies of wound dressings were significantly reduced, so the patients felt comfortable. According to results of post-operation follow-up for6to12months, all the skin grafts of the wounds healed by using the combined therapy presented a good color; texture of the skin grafts was soft and wear-resistant; contracture and secondary dysfunction did not occur; the appearance of healed donor sites was good; and the wounds did not recur.Conclusion1, VAC can promote the growth of granulation tissue of a wound and the clearance of bacteria on an infected wound, thereby providing good wound base conditions for artificial dermis grafting.2, VAC can promote the process of vascular collageniztion of artificial dermis, shorten time needed in vascular collageniztion of artificial dermis and improve the success rate of grafting through its biological effects (controlling of infection, mitigation of inflammatory reaction and induction of tissue cell proliferation).3, the combined therapy of VAC and artificial dermis grafting is a safe, simple, convenient, effective and ideal approach for wound treatment and is especially applicable to treatment of a variety of refractory wounds. |
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