Autologous Skin Grafts Research Articles

A single-stage bilayered skin reconstruction using Glyaderm® as an acellular dermal regeneration template results in improved scar quality: an intra-individual randomized controlled trial

Absence of almost the entire reticular dermal layer is inherent to the use of autologous split-thickness skin grafting (STSG) to close full-thickness wounds, often resulting in hypertrophic scars and contractures. Many dermal substitutes have been developed, but unfortunately most have varying results in terms of cosmetic and/or functional improvement as well as patient satisfaction, in addition to high costs. Bilayered skin reconstruction using the human-derived glycerolized acellular dermis (Glyaderm®) has been reported to result in significantly improved scar quality using a two-step procedure. Unlike the necessary two-step procedure for most commercially available dermal substitutes, in this study we aimed to investigate the use of Glyaderm® in a more cost-effective single-stage engrafting. This is a method which, if autografts are available, is preferred by the majority of surgeons given the reduction in costs, hospitalization time and infection rate. A prospective, randomized, controlled, intra-individual, single-blinded study was performed, investigating the simultaneous application of Glyaderm® and STSG vs. STSG alone in full-thickness burns or comparable deep skin defects. During the acute phase, bacterial load, graft take and time to wound closure were assessed and were the primary outcomes. Aesthetic and functional results (secondary outcomes) were evaluated at 3, 6, 9 and 12months follow-up using subjective and objective scar measurement tools. Biopsies for histological analysis were taken at 3 and 12months. A total of 66 patients representing 82 wound comparisons were included. Graft take (>95%), pain management and healing time were comparable in both groups. At 1year follow-up, the overall Patient and Observer Scar Assessment Scale assessed by the patient was significantly in favour of sites where Glyaderm® was used. Not infrequently, patients attributed this difference to improved skin sensation. Histological analysis showed the presence of a well-formed neodermis, with donor elastin present for up to 12months. A single-stage bilayered reconstruction with Glyaderm® and STSG results in optimal graft take without loss of Glyaderm® nor the overlaying autografts due to infection. The presence of elastin in the neodermis was demonstrated during long-term follow-up in all but one patient, which is a crucial factor contributing to the significantly improved overall scar quality as evaluated by the blinded patients. The trial was registered on clinicaltrials.gov and received the following registration code: NCT01033604.

Skin Tissue Engineering Advances in Burns: A Brief Introduction to the Past, the Present, and the Future Potential.

Burn injuries are a severe form of skin damage with a significant risk of scarring and systemic sequelae. Approximately 11 million individuals worldwide suffer burn injuries annually, with 180,000 people dying due to their injuries. Wound healing is considered the main determinant for the survival of severe burns and remains a challenge. The surgical treatment of burn wounds entails debridement of necrotic tissue, and the wound is covered with autologous skin substitutes taken from healthy donor areas. Autologous skin transplantation is still considered to be the gold standard for wound repair. However, autologous skin grafts are not always possible, especially in cases with extensive burns and limited donor sites. Allografts from human cadaver skin and xenografts from pig skin may be used in these situations to cover the wounds temporarily. Alternatively, dermal analogs are used until permanent coverage with autologous skin grafts or artificial skins can be achieved, requiring staged procedures to prolong the healing times with the associated risks of local and systemic infection. Over the last few decades, the wound healing process through tissue-engineered skin substitutes has significantly enhanced as the advances in intensive care ensuring early survival have led to the need to repair large skin defects. The focus has shifted from survival to the quality of survival, necessitating accelerated wound repair. This special volume of JBCR is dedicated to the discoveries, developments, and applications leading the reader into the past, present, and future perspectives of skin tissue engineering in burn injuries.

Advances in Skin Tissue Engineering and Regenerative Medicine.

There are an estimated 500,000 patients treated with full-thickness wounds in the United States every year. Fire-related burn injuries are among the most common and devastating types of wounds that require advanced clinical treatment. Autologous split-thickness skin grafting is the clinical gold standard for the treatment of large burn wounds. However, skin grafting has several limitations, particularly in large burn wounds, where there may be a limited area of non-wounded skin to use for grafting. Non-cellular dermal substitutes have been developed but have their own challenges; they are expensive to produce, may require immunosuppression depending on design and allogenic cell inclusion. There is a need for more advanced treatments for devastating burns and wounds. This manuscript provides a brief overview of some recent advances in wound care, including the use of advanced biomaterials, cell-based therapies for wound healing, biological skin substitutes, biological scaffolds, spray on skin and skin bioprinting. Finally, we provide insight into the future of wound care and technological areas that need to be addressed to support the development and incorporation of these technologies.

A Risk-Benefit Review of Currently Used Dermal Substitutes for Burn Wounds.

While split-thickness autologous skin grafts remain the most common method of definitive burn wound closure, dermal substitutes have emerged as an attractive option. There are many advantages of utilizing a dermal substitute, notably reducing the need for donor tissue and subsequent iatrogenic creation of a secondary wound. However, there are disadvantages with each that most be weighed and factored into the decision. And most come at a high initial financial cost. There is little comparative literature of the various available and emerging products. This analysis was performed to objectively present risks and benefits of each option.

Research progress and challenges of bioprinting in wound dressing and healing: Bibliometrics-based analysis and perspectives.

As the body's largest organ, the skin has important roles in barrier function, immune response, prevention of water loss and excretion of waste. Patients with extensive and severe skin lesions would die due to insufficient graftable skin. Commonly used treatments include autologous skin grafts, allogeneic/allogeneic skin grafts, cytoactive factors, cell therapy, and dermal substitutes. However, traditional treatment methods are still inadequate regarding skin repair time, treatment costs, and treatment results. In recent years, the rapid development of bioprinting technology has provided new ideas to solve the above-mentioned challenges. This review describes the principles of bioprinting technology and research advances in wound dressing and healing. This review features a data mining and statistical analysis of this topic through bibliometrics. The annual publications on this topic, participating countries, and institutions were used to understand the development history. Keyword analysis was used to understand the focus of investigation and challenges in this topic. According to bibliometric analysis, bioprinting in wound dressing and healing is in an explosive phase, and future research should focus on discovering new cell sources, innovative bioink development, and developing large-scale printing technology processes.

Multifunctional sponge scaffold loaded with concentrated growth factors for promoting wound healing

Although both are applied in regenerative medicine, acellular dermal matrix (ADM) and concentrated growth factor (CGF) have their respective shortcoming: The functioning of CGF is often hindered by sudden release effects, among other problems, and ADM can only be used in outer dressing for wound healing. In this study, a compound network with physical-chemical double cross-linking was constructed using chemical cross-linking and the intertwining of ADM and chitosan chains under freezing conditions; equipped with good biocompatibility and cell/tissue affinity, the heparin-modified composite scaffold was able to significantly promote cell adhesion and proliferation to achieve adequate fixation and slow down the release of CGF; polydopamine nanoparticles having excellent near-infrared light photothermal conversion ability could significantly promote the survival of rat autologous skin grafts. In a word, this multifunctional composite scaffold is a promising new type of implant biomaterial capable of delivering CGF to promote the healing of full-thickness skin defects.

Prognostic Analysis of Skin Scar Loosening and Tissue-Expansive Autologous Skin Grafting in the Treatment of Skin Postburn Scars.

This study aims to observe and investigate the clinical value of scar loosening and tissue-expansive autologous skin grafting in the treatment of postburn scars and independent risk characteristics for surgery-related complications. We retrospectively analyzed 94 cases with postburn scars, and all patients were treated with scar loosening and autologous skin grafting. Overall therapeutic effects were evaluated using the standard of cure and improvement of clinical diseases. Burn Specific Health Scale-brief was used to analyze patients' quality of life. The visual analog scale scores were used to analyze esthetic satisfaction. Surgery-related complications were recorded, and logistic regression model was used to analyze independent factors affecting surgery-related complications. As for overall efficacy evaluation, 50 cases were cured, 19 cases were markedly improved, 17 cases improved, and 8 cases were detected and tested, and the overall effective rate was 91.4%. The Burn Specific Health Scale-brief and visual analog scale score showed a trend of increasing gradually. It indicated that the patients were satisfied with the operation and their quality of life was improved. The logistic regression model showed that history of skin disease (OR=1.53 (1.08-2.16), P =0.02) and skin area (OR=2.50 (1.22-4.50), P <0.01) were significantly associated with surgery-related complications. Scar loosening and autologous skin grafting is a safe and effective treatment. The history of skin disease and skin area was the independent factors for surgery-related complications.

Autologous wound margin point columnar full-thickness skin grafting combined with negative pressure wound therapy improves wound healing in refractory diabetic foot ulcers.

Diabetic lower extremity ulcers (DLEUs) are a severe complication of diabetes mellitus (DM) and are difficult to heal. This study aimed to explore the efficacy of autologous point columnar full-thickness skin graft taken from the ulcer wound margin combined with negative pressure wound therapy (NPWT) in refractory DLEUs. This is a prospective cohort study. A total of 40 inpatients with refractory DLEUs were recruited in the Diabetes Foot Center of Guangxi Zhuang Autonomous Region People's Hospital from October 2019 to November 2021. According to the doctors' professional suggestions and the patients' personal wishes, these enrolled patients were divided into two groups based on different topical wound management: the graft group (n=18) and the conventional wound therapeutic (CWT) group (n=22). The efficacy evaluations included the time to complete re-epithelialization of the wound and healing speed within 14 days of graft treatment or after 14 days of graft treatment in the two groups. Before the treatment, the graft group had a significantly larger ulcer area than the CWT group [27.22 (15.28, 46.59) versus 10.92 (7.00, 24.93) cm2 , P < .01]. However, the time to complete wound re-epithelialization in the graft group was shorter than in the CWT group [58.22 ± 30.60 versus 86.09 ± 49.54 d, P < .05]. Meanwhile, the healing speed in graft group was markedly faster than in CWT group, whether within 14 days [0.60 (0.40, 0.92) versus 0.16 (0.07, 0.34) cm2 /d, P < .01] or after 14 days of graft treatment [0.57 (0.45, 0.91) versus 0.13 (0.08, 0.27) cm2 /d, P < .01]. However, the total treatment cost in the graft group was lower than in the CWT group [419.59 ± 137.20 versus 663.97 ± 497.02 $, P < .05]. The novel treatment modality of autologous full-thickness skin graft taken from the ulcer wound margin combined with NPWT has hereby proposed for the first time, and is a safe, effective, and reliable method with a good performance-to-cost ratio to promote wound healing and shorten the healing time for DLEUs.

Systematic Review of Incidence of Cancer in Burns

INTRODUCTION: The incidences of malignant transformation of burn scar are well documented. The most common carcinoma in burned areas is squamous cell carcinoma (SCC), followed by basal cell carcinoma (BCC). However, there is a lack of information regarding the rate of SCC and BCC onset after burn injury and if burn injury itself attributes to such malignancies. METHODS: A systematic review was performed according to the Preferred Reporting Section for Systematic Review and Meta-analysis (PRISMA) guidelines to retrospectively determine the incidence of cancer development, mainly squamous cell carcinoma and basal cell carcinoma, reported in burn studies. Two independent reviewers screened eligibility and selected 120 studies (75 SCC, 23 BCC, 32 others) from 330 published studies between 1946 and July 16, 2021. RESULTS: The patients’ age at the onset of burn exhibited a negative correlation with the length of the latency period in both SCC and BCC studies. The mean latency period for BCC was 40.8 + 22 years compared with SCC, 32.2 + 22.3 years. The latency period for SCC development after burn was lower for males (28.8 + 23.48 years) compared with females (38.9 + 20 years; Figure). Around 5% of studies reported scars in the grafted sites. Wide local excision followed by autologous skin grafting was the primary line of treatment in most of the studies; however, there was no consensus regarding the treatment of recurrence of carcinoma.Figure.: BCC, basal cell carcinoma; SCC, squamous cell carcinoma.CONCLUSION: Future retrospective studies with a higher number of patients are warranted to determine whether burn injury accelerates cancer progression.

Application of collagen-chondroitin sulfate scaffolds with different pore sizes combined with acidic fibroblast growth factor in repairing full thickness skin defects in nude mice

Wound healing of skin defects is complex. For the treatment of large and deep wounds, it is a good alternative to accept artificial dermis grafting at the first stage surgery, and autologous split-thickness skin grafting 2–3 weeks later at the second stage surgery. In addition, the effectiveness of numerous cytokines such as fibroblast growth factor (FGF) on wounds healing has been widely researched. The traditional view is that direct external application or in vivo injection of exogenous FGFs may not achieve the desired therapeutic effect as the effective concentration cannot be maintained for a long time. Therefore, some researchers have tried to integrate various cytokines into skin substitutes for combined application. However, we believe that considering the current situation, it is still difficult to achieve mass production of these types of artificial dermis. Here, we manufactured a collagen-chondroitin sulfate scaffold material by imitating the marketed artificial dermis materials. Then, we combined it with recombinant human acidic FGF in a single full dose during the first-stage artificial dermis transplantation, which is simple and completely feasible but always controversial in the current clinical work, to explore whether this combinatorial therapy could serve as an efficient way wound healing in the Balb/c-nu mice full-thickness skin defect model.

Comparison of Glyaderm with different dermal substitute matrices in a porcine wound model

BackgroundThe closure of extensive burn wounds with widely expanded autologous split-thickness skin grafts (STSG) is associated with undesirable scar formation and contraction, due to the lack of dermis. Various materials for dermal replacement have been developed, either of xenogeneic, allogeneic or synthetic origin and are placed in the wound underneath a thin STSG in order to improve scar quality. In this study, a porcine wound model was used to compare several commercially available acellular dermal substitutes with an acellular dermal substitute prepared from glycerol preserved human skin: GlyadermⓇ. MethodsAntigenic components of the allografts were removed by incubation in the 0.06 M NaOH solution. In the first experiments, the dermal substitutes were applied to full thickness wounds and covered simultaneously with STSG. Controls were covered with STSG only. The wound healing response was analyzed for 8 weeks, both macroscopically and histologically. The Mann-Whitney U test was used for statistical analysis. In the second series of experiments, GlyadermⓇ was applied in a two-stage procedure in comparison to Integra. The STSG was placed on the dermal substitutes one week later. ResultsIn the first series, the inflammatory response and myofibroblast influx in GlyadermⓇ were limited, indicating possible beneficial outcomes on final wound healing results. The survival of the STSG on the acellular dermis was lower compared to the control wounds. Second series: the take of the STSG was the same as in the controls, but additionally wound contraction was reduced. The application of GlyadermⓇ was non-inferior to Integra. ConclusionGlyadermⓇ can be successfully used for the reduction of wound contraction when applied in a two-stage procedure.

Management of wounds with exposed bone structures using an induced-membrane followed by polymethyl methacrylate and second-stage skin grafting in the elderly with a 3-year follow-up.

The treatment of traumatic wounds with exposed bone or tendons is often challenging. An induced membrane (IM) is used to reconstruct bone defects, as it provides an effective and sufficient blood supply for bone and soft-tissue reconstruction. This study explored a novel two-stage strategy for wound management, consisting of initial wound coverage with polymethyl methacrylate (PMMA) and an autologous split-thickness skin graft under the IM. Fifty inpatients were enrolled from December 2016 to December 2019. Each patient underwent reconstruction according to a two-stage process. In the first stage, the defect area was thoroughly debrided, and the freshly treated wound was then covered using PMMA cement. After 4-6 weeks, during the second stage, the PMMA cement was removed to reveal an IM covering the exposed bone and tendon. An autologous split-thickness skin graft was then performed. Haematoxylin and eosin (H&E) staining and immunohistochemical analysis of vascular endothelial growth factor (VEGF), CD31 and CD34 were used to evaluate the IM and compare it with the normal periosteal membrane (PM). The psychological status and the Lower Extremity Function Scale (LEFS) as well as any complications were recorded at follow-up. We found that all skin grafts survived and evidenced no necrosis or infection. H&E staining revealed vascularised tissue in the IM, and immunohistochemistry showed a larger number of VEGF-, CD31- and CD34-positive cells in the IM than in the normal PM. The duration of healing in the group was 5.40 ± 1.32 months with a mean number of debridement procedures of 1.92 ± 0.60. There were two patients with reulceration in the group. The self-rating anxiety scale scores ranged from 35 to 60 (mean 48.02 ± 8.12). Postoperatively, the LEFS score was 50.10 ± 9.77. Finally, our strategy for the management of a non-healing wound in the lower extremities, consisting of an IM in combination with skin grafting, was effective, especially in cases in which bony structures were exposed in the elderly. The morbidity rate was low.

Procédé de greffes enfouies en situation d’échecs d’autogreffes cutanées

Local conditions can lead to a failure of traditional skin grafts. We propose here our technique about the realization of autologous skin graft using it buried chipped grafts, for wounds in failure of treatments or at risk of failure. The protocol includes cutting the skin graft within little squared pieces of a few millimeters of length, that are then buried directly deep into the wound. We can then obtain little islands of epidermisation on the random places of the wound that will heal by confluence of those epidermal islands.

Length of Stay and Costs with Autologous Skin Cell Suspension Versus Split-Thickness Skin Grafts: Burn Care Data from US Centers.

IntroductionAutologous skin cell suspension (ASCS) significantly reduces donor skin requirements versus conventional split-thickness skin grafts (STSG) for thermal burn treatment. In analyses using the Burn-medical counter measure Effectiveness Assessment Cost Outcomes Nexus (BEACON) model, ASCS was associated with shorter hospital length of stay (LOS) and cost savings versus STSG. This study hypothesized that daily practice data from the USA would support these findings.MethodsElectronic medical record data from 500 healthcare facilities (January 2019–August 2020) were used to match adult patients who received inpatient burn treatment with ASCS (± STSG) to patients treated with STSG alone on the basis of sex, age, percent total body surface area (TBSA), and comorbidities. Based on BEACON analyses, LOS was assumed to represent 70% of total costs and used as a proxy to assess the data. Mean LOS, costs, and the incremental revenue associated with inpatient capacity changes were calculated.ResultsA total of 151 ASCS and 2443 STSG patients were identified: 63.0% were male and average age was 44.5 years. Eight-one matches were made between cohorts. LOS was 21.7 days with ASCS and 25.0 days with STSG alone (difference 3.3 days [13.2%]). LOS was lower with ASCS than STSG in four of five TBSA intervals. The LOS difference led to hospital bed cost savings of $25,864 per ASCS patient; overall cost savings were $36,949 per patient. Similar cost savings were observed in TBSA groupings < 20% and ≥ 20%. The reduced LOS with ASCS translated into an increased capacity of 2.2 inpatients/bed annually, which increased hospital revenue by $92,283/burn unit bed annually.ConclusionsReal-world data show that ASCS (± STSG) is associated with reduced LOS and cost savings versus STSG alone across all burn sizes, supporting the validity of the BEACON analyses. ASCS use may also increase patient capacity and throughput, leading to increased hospital revenue.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02306-y.

Outcomes Following Use of Negative-Pressure Wound Therapy Over Autologous Meshed and Non-Meshed Skin Grafts.

Negative-pressure wound therapy (NPWT) over split thickness skin grafts can control exudate, decrease infection rates, and improve revascularization. However, no study specifically addresses differences in outcomes between meshed/perforated and non-meshed autologous skin grafts dressed with NPWT. Through retrospective chart review, patients undergoing autologous split thickness skin grafting with a NPWT dressing for any burn injury over a 10-month period were identified. Data on etiology, graft take, meshed/perforated or non-meshed graft, graft size, and seroma/hematoma incidence were collected. Our study included 123 patients who had STSG with NPWT and consisted of 57% males, 57% Caucasian, and an average age of 41. Burn injury etiologies consisted of scald (55%), chemical (25%), flame (15%), and contact (5%). Average 2nd degree TBSA in our cohort was 2.34%, 3rd degree TBSA 4.50%, and total TBSA 5.35%. 66.7% of patients received non-meshed grafts, and these patients had an average graft area of 76.5 cm2. 33.3% of patients received meshed grafts, with an average graft area of 163.5 cm2. Non-meshed burn grafts were significantly smaller than meshed grafts (P = .04). There was 100% graft take and 0% seroma/hematoma formation in all patients. Data was analyzed using an unpaired student's T test and ANOVA testing. There were no statistically significant differences in patient demographics, or burn etiology. There exist many options for dressings after repair of burn injuries, each with its own unique advantages. There were, however, no differences in graft take or incidence of seroma/hematoma formation using a NPWT dressing over autologous meshed grafts vs non-meshed grafts. Our data shows that NPWT use as a bolster dressing is safe and efficacious overlying meshed skin grafts and non-meshed grafts.

Basic fibroblast growth factor-impregnated collagen gelatin sponge completes formation of dermis-like tissue within 2 weeks: Aprospective cohort study.

IntroductionThis study included patients who underwent full-thickness skin reconstruction using a two-stage procedure comprising basic fibroblast growth factor-impregnated collagen gelatin sponge (bFGF-CGS) implantation and autologous skin grafting, and the take rate of skin grafts was compared between groups of patients who underwent autologous skin grafting after a waiting period of <2 weeks or ≥2 weeks.MethodsAn acute, full-thickness skin defect was treated with thorough debridement of contaminated/necrotic tissue, followed by washing with saline and hemostasis with electrocautery. Then, an FGF-CGS was fixed to the skin defect wound using non-absorbable sutures, and after confirming regeneration of sufficient dermis-like tissue, the second-stage autologous skin grafting was performed for wound closure. Patients were divided into two groups according to the waiting period before the second operation, namely, <2 weeks (early group) and ≥2 weeks (late group), and the take rate of skin grafts was compared.ResultsWe enrolled and treated 25 cases (18 men, 7 women; mean age: 49 [range 2–86] years). The mean take rate of skin grafts was 93% (range 80%–100%) in the early group and 92% (range 65%–100%) in the late group, with no significant difference between the two groups. There was a significant difference between the groups in mean time to complete healing: 25.2 ± 9.7 days in the early group vs 44.7 ± 27 days in the late group (p < 0.05).ConclusionOur data suggest that bFGF-CGF can form dermis-like granulation tissue with sufficient quality as a graft bed for skin transplantation within 2 weeks.

Biomarkers of Skin Graft Healing in Venous Leg Ulcers.

There is a need for biomarkers that predict the success of transplantation of venous leg ulcers (with autologous split-thickness skin grafts). The primary objective of this exploratory study was to investigate the association between split-thickness skin graft healing in venous leg ulcers and candidate wound fluid biomarkers representing inflammatory cell and endogenous proteinase activities, and bioactivity. A secondary objective was to compare biomarker levels of the 17 venous leg ulcers with sterile split-thickness skin graft donor-site wounds in another 10 patients with venous leg ulcers. Wound fluids were collected for 24 h using a validated method. The concentration of pre-operative matrix metalloproteinase-9 in wound fluid was higher in venous leg ulcers showing good healing (n = 10) than in venous leg ulcers showing poor healing (n = 7) 12 weeks after transplantation with meshed split-thickness skin grafts. The diagnostic value of matrix metalloproteinase-9 was good according to receiver-operating characteristic curve analysis. Matrix metalloproteinase activity in wound fluids from split-thickness skin graft donor-site wounds increased as a function of time and healing, but was still lower than matrix metalloproteinase activity in venous leg ulcer wound fluids, which showed increased levels of most biomarkers except for matrix metalloproteinase-9 and matrix metalloproteinase-2. In conclusion, wound fluid matrix metalloproteinase-9 concentration is a potential predictive biomarker of split-thickness skin graft healing in venous leg ulcers.

Effects of comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome

Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.

Disrupting mechanotransduction decreases fibrosis and contracture in split-thickness skin grafting.

Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.

Enzymatic debridement: past, present, and future

Introduction Early surgical debridement of the deep second and third-degree burns is still the standard of care (SOC) to prepare the wound bed for skin grafting. However, this technique has some drawbacks that explain the growing interest in enzymatic debridement as an alternative. In this article, we provide a historic overview as well as the current state-of-the-art and future prospective of this type of non-surgical debridement. Materials and methods A narrative review of the available literature was conducted using a systematic search. Results A total of 32 articles were included. The only enzyme mixture still used nowadays for burn eschar removal is bromelain-based. There is increasing evidence that this type of enzymatic debridement is a powerful tool to selectively remove the eschar in deep burns, thereby reducing the need for autologous skin grafting compared to surgical SOC. Moreover, off-label use of enzymatic debridement with NexoBrid® (facial, pediatric, and >15%TBSA burns) has proven to be effective and safe. Conclusion There is increasing evidence that bedside administered NexoBrid®, preferably under regional anesthesia, is a powerful tool for selective burn eschar removal. However, the clinical wound bed evaluation post-NexoBrid® procedure in relation to the optimal treatment decision—conservative treatment vs. surgery—is not yet completely elucidated. More high-quality prospective clinical trials are necessary to compare enzymatic debridement of objectively confirmed deep burns with the current standard treatment and assess the effectiveness of the eschar removal, the need for surgery, the healing time of such wounds, and the long-term scar quality.