Application Of External Tissue Expansion Technique In The Treatment Of Soft Tissue Defects

Background:How to close large skin and soft tissue defects rapidly and safely has always been a concern for surgeons.At present,a variety of reconstruction methods can be selected,such as dressing change,suture,skin grafting,volume expansion,and skin flaps.For soft tissue defects that cannot be closed by direct suture,it is often necessary to choose more complicated reconstruction methods to close the skin and soft tissue defects.Traditional skin transplantation and skin flap need to create a donor site,with the poor appearance of the wound,which cannot meet the needs for aesthetics.At the same time,skin flaps have high requirements for the surgeon,and the success rate of the operation is closely related to the proficiency of the surgeon.However,volume expansion requires subcutaneous expander,which has a long expansion cycle and many complications.Therefore,surgeons have been looking for a practical,simple and effective method to repair and reconstruct skin and soft tissue defects,which can not only complete the closure of skin and soft tissue defects but also improve the quality of postoperative healing procedure of patients.In this context,external tissue expansion technique is expected to be a new choice for the reconstruction of skin and soft tissue defects.It uses the viscoelastic properties of the skin to "mobilize" the skin and promote the biological creep of the skin to complete the closure of skin and soft tissue defects.Unlike volume expansion,it does not need a built-in expander.And there is no need to create a new donor site wound,and the luster,appearance,and elasticity of the healed skin are consistent with the original skin.In recent years,skin and soft tissue external expansion technique has been widely used in the closure of various types of skin and soft tissue defects,and various commercial skin and soft tissue external expanders have emerged in an endless fashion.Considering the lack of uniform naming,in this paper,we name all the devices based on the same principle as external tissue expansion devices.The relevant studies are mainly case reports,and there is a lack of systematic research and analysis and high-quality clinical trials to evaluate the safety of its application.At present,the safety and effectiveness of its clinical application are still controversial,and the healing mechanism of skin and soft tissue defects under external expansion is not clear.Based on the problems above,this study focuses on the key issues in the clinical application of external skin soft tissue expansion technology.First,a Metaanalysis was conducted to evaluate the safety and effectiveness of external skin soft tissue expansion in various types of skin and soft tissue defects,that is,the first part of this study:Safety and efficacy of external skin soft tissue expansion technique in skin and soft tissue defects: a Meta-analysis.Based on the results of the first part of the study,we found the limitations of the current external tissue expansion technique.On the basis of this,we designed a modified external tissue expansion technique.The clinical efficacy of the modified external expansion technique in the closure of various types of skin and soft tissue defects was evaluated.In the third part of this study,the expanded animal and human skin samples were collected to explore the underlying mechanisms.Method:1.Safety and efficacy of external tissue expansion technique in the treatment of soft tissue defects: A single-arm Meta-analysisThis part conducts a systematic review and Meta-analysis of the efficacy and safety of ex vivo tissue expansion techniques.A comprehensive search of Pub Med/Medline,Embase,Cochrane Library(Wiley Online library),and Web of Science for all studies using external skin and soft tissue expansion techniques in the treatment of skin and soft tissue defects was performed.The search time was from the beginning of the journal to February 17,2022.Two researchers independently screened the literature,extracted data,and assessed the quality of the literature.Meta-analysis was performed using R studio software.To evaluate the median healing time and healing rate of external tissue expansion technique in the closure of skin and soft tissue defects caused by different reasons,a single arm Meta-analysis was made.The complications related to external tissue expansion technique were analyzed.2.Application of modified external tissue expansion technique in repair of skin and soft tissue defects: a retrospective cohort studyThis study was a retrospective cohort study.The test cohort was patients who underwent modified external skin soft tissue expansion,and the control cohort was patients who underwent skin grafting for closure of skin soft tissue defects.The clinical data of patients were collected through the medical record system and big data system of Changhai Hospital.The outcome indexes were closing time,closing rate,and scar hyperplasia after healing.In this study,the Patient Scar Assessment Scale was used to evaluate the scar hyperplasia.3.Preliminary exploration of the closure mechanism of skin and soft tissue defects mediated by external tissue expansion techniqueThe morphological changes of the dermal layer of a pig were observed by HE staining on the 3rd,7th,10 th and 14 th day after the skin soft tissue expansion.The morphological changes of human skin dermis after external expansion were observed by HE staining and Masson staining.The cell proliferation and differentiation after external expansion were preliminarily explored by immunohistochemistry and immunofluorescence.Results:1.Safety and efficacy of external tissue expansion technique in the treatment of soft tissue defects: A single-arm Meta-analysisA total of 66 studies with 22 different types of external tissue expansion devices met the inclusion criteria.We performed a descriptive analysis of different kinds of devices.A single-arm Meta-analysis was performed to evaluate the efficacy and safety of the external tissue expansion technique for different aetiologies.The pooled mean wound healing time among patients with defects after fasciotomy was 10.548 days [95% confidence interval(CI)= 5.796–15.299].The pooled median wound healing times of patients with defects after excisional surgery,trauma and chronic ulcers were 11.218 days(95% CI = 6.183-16.253),11.561 days(95% CI = 7.062-16.060)and 15.956 days(95% CI = 11.916-19.996),respectively.The pooled wound healing rates of patients with defects after fasciotomy,excisional surgery,trauma,chronic ulcers and abdominal defects were 93.8%(95% CI=87.1-98.2%),97.2%(95%CI=92.2-99.7%),97.0%(95%CI=91.2-99.8%)and 99.5%(95%CI=97.6-100%)respectively.We performed a subgroup analysis in patients with diabetic ulcers and open abdominal wounds.The pooled median wound healing time of patients with diabetic ulcers was 11.730 days(95% CI = 10.334-13.125).The pooled median wound healing time of patients with open abdomen defects was 48.810 days(95% CI =35.557–62.063)and the pooled successful healing rate was 68.8%(95% CI = 45.9-88.1%).A total of 55 studies reported complications associated with external skin soft tissue expansion(including 8 studies that reported no complications),involving 1686 patients,of whom 265(15.7%)had complication.The most common complication was wound dehiscence(n=53,3.14%).Other common complications included hypertrophic scar(n=51,3.02%),infection(n=37,2.19%),severe pain(n=26,1.54%),and skin necrosis(n=21,1.25%).2.Application of modified external tissue expansion technique in repair of skin and soft tissue defects: a retrospective cohort studyA total of 159 patients were enrolled in this study,including 20 patients in the case group and 139 patients in the control group.Before propensity score matching,the median healing time of the test group and the control group was 11.00 [7.00-15.25] days VS 7.0[6.00-9.00] days,p < 0.05.The healing rate was 80% VS 90.6%(p=0.292).After propensity score matching,the healing time of the two groups was 11.00 days [7.00-15.25] VS 8.0 days[6.75-11.75],p=0.575;The healing rate was 80% VS 90%,p=0.658.Multivariate Cox regression analysis showed that surgical method was not an independent risk factor for the healing of patients.A total of 105 patients completed the assessment of scar hyperplasia one year after operation,and 99 patients were finally included.The subjective scar score of patients after external tissue expansion was better than that of patients in skin grafting group(13.00±3.88 vs.22.4±12.38,p=0.004).After propensity score matching,the subjective score of scar of patients in external skin and soft tissue expansion group was 13.00±3.88 points,and that of patients in skin grafting group was 21.44±12.96 points,p=0.018.3.Preliminary exploration of the closure mechanism of skin and soft tissue defects mediated by external tissue expansion techniqueIn general,intraoperative closure was achieved by external tissue expansion technique in an experimental pig.The histological morphology of the dermis of porcine skin after external expansion was observed.After external expansion,the collagen fibers stretched and extended in the direction of force,and the collagen fibers were parallel to the epidermis.Three days after external expansion,the collagen fibers stretched parallel to the epidermis,and the epidermis became thinner.Immunofluorescence results showed that the expression of Ki67 in the basal layer of skin was increased and the expression of Keratin10 was decreased 3 days after external tissue expansion of human skin,suggesting that the cell proliferation was enhanced,and the cells did not express more mature cell markers.Conclusion:1.This Meta-analysis has proved the effectiveness of external tissue expansion technique in the treatment of skin and soft tissue defects,but there are still some technical defects to be improved in its clinical application.2.There is no significant difference in the closure efficiency of skin and soft tissue defects between the modified skin and soft tissue expansion technique group and the skin grafting surgery,and it can significantly improve the quality of postoperative healing of patients.The defects’ location may be a key factor affecting the defects’ closure.However,limited by the number of patients included in the trial cohort,the data of this study are not highly representative,and the effectiveness of its clinical application still needs to be further evaluated by high-quality randomized controlled trials and long-term patient follow-up.3.External expansion of skin soft tissue may induce skin regeneration by stimulating epidermal cell proliferation and affecting cell differentiation.