Regeneration and expansion of autologous full-thickness skin through a self-propagating autologous skin graft technology.
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ABSTRACT:
SUBMITTER: Patterson CW
PROVIDER: S-EPMC6935643 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
Regeneration and expansion of autologous full-thickness skin through a self-propagating autologous skin graft technology.
Patterson Charles W CW Stark Matthew M Sharma Silpa S Mundinger Gerhard S GS
Clinical case reports 20191106 12
New autologous skin regeneration technology yielded full-thickness skin as evidenced by clinical observation and skin biopsy 5 months after surgery, providing relief for debilitating split-thickness skin graft contracture in a pediatric burn case. ...[more]
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Project description:BackgroundParastomal hernia is a common complication of stoma formation and the methods of repair available today are unsatisfactory with high recurrence and complication rates. To improve outcome after surgical repair of parastomal hernia, a surgical method using autologous full-thickness skin grafts as intraperitoneal reinforcement has been developed. The purpose of this study was to evaluate the feasibility of this novel surgical technique in the repair of parastomal hernia.MethodsA pilot study was conducted between January 2018 and June 2019 on four patients with symptomatic parastomal hernia. They had a laparotomy with suture reduction of the hernia and reinforcement of the abdominal wall with autologous full-thickness skin. They were then monitored for at least 1 year postoperatively for technique-related complications and recurrence.ResultsNo major technique-related complications were noted during the follow-up Two patients developed a recurrent parastomal hernia at the long term follow-up. The other two had no recurrence.ConclusionsAutologous full-thickness skin graft as reinforcement in parastomal hernia repair is feasible and should be evaluated in a larger clinical trial.
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Project description:Stable closure of full-thickness burn wounds remains a limitation to recovery from burns of greater than 50% of the total body surface area (TBSA). Hypothetically, engineered skin substitutes (ESS) consisting of autologous keratinocytes and fibroblasts attached to collagen-based scaffolds may reduce requirements for donor skin, and decrease mortality. ESS were prepared from split-thickness skin biopsies collected after enrollment of 16 pediatric burn patients into an approved study protocol. ESS and split-thickness autograft (AG) were applied to 15 subjects with full-thickness burns involving a mean of 76.9% TBSA. Data consisted of photographs, tracings of donor skin and healed wounds, comparison of mortality with the National Burn Repository, correlation of TBSA closed wounds with TBSA full-thickness burn, frequencies of regrafting, and immunoreactivity to the biopolymer scaffold. One subject expired before ESS application, and 15 subjects received 2056 ESS grafts. The ratio of closed wound to donor areas was 108.7?±?9.7 for ESS compared with a maximum of 4.0?±?0.0 for AG. Mortality for enrolled subjects was 6.25%, and 30.3% for a comparable population from the National Burn Repository (P < .05). Engraftment was 83.5?±?2.0% for ESS and 96.5?±?0.9% for AG. Percentage TBSA closed was 29.9?±?3.3% for ESS, and 47.0?±?2.0% for AG. These values were significantly different between the graft types. Correlation of % TBSA closed with ESS with % TBSA full-thickness burn generated an R value of 0.65 (P < .001). These results indicate that autologous ESS reduce mortality and requirements for donor skin harvesting, for grafting of full-thickness burns of greater than 50% TBSA.
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Project description:BackgroundParastomal hernia is a common complication of an enterostomy and can have a significant impact on health-related quality of life. Currently used methods of repair have high recurrence rates and considerable risk for complications. We have developed a new technique for parastomal hernia repair that uses full-thickness skin graft as reinforcement.MethodsThis study protocol describes a multicentre randomised controlled trial on parastomal hernia repair comparing a new full-thickness skin graft technique with conventional synthetic composite mesh as reinforcement of the abdominal wall. Patients with a symptomatic parastomal hernia will be included and followed up at 3, 12 and 36 months, with surgical complication as the primary outcome. Secondary outcomes will be recurrence rate and health-related quality of life assessed with VHPQ, EORTC C30 and CR29. Tissue biology and collagen metabolism will be investigated pre- and postoperatively using biopsies of the abdominal wall fascia and blood samples.DiscussionParastomal hernia constitutes a major clinical problem where the prospects of a good result after hernia repair are presently poor. This new method of repair with full-thickness skin grafting could be a new alternative in our surgical toolbox, but before then, it must be evaluated properly.Trial registrationClinicalTrials.gov NCT03667287. Registered on September 12, 2018.
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Project description:Full-thickness deficiency of eyelid tissues can result in coloboma or retraction or both. Here we report our initial experience on the use of auricular skin-cartilage sandwich graft technique for full-thickness eyelid deformities. Five patients (4-32 years) underwent the procedure. Patients with full-thickness eyelid deformity were included. Three patients were operated for large-sized coloboma and two for eyelid retraction. One patient had congenital, and four patients had acquired etiology. The following parameters were specifically assessed: correction of deformity, ocular surface problems, graft status, and epithelization of skin-cartilage graft. All the patients had a good correction of eyelid position, except one patient who had severe eyelid retraction (8 mm) at presentation. None of our patients had corneal erosion/defect, persistent ocular surface redness, or graft loss. The auricular skin-cartilage sandwich graft technique produces optimal results with no graft loss. Advancement of orbicularis muscle in between the auricular skin and cartilage grafts (sandwich technique) is an imperative step that leads to the survival of both grafts.
| S-EPMC9240525 | biostudies-literature
Project description:Despite differing etiologies, acute thermal burn injuries and full-thickness (FT) skin defects are associated with similar therapeutic challenges. When not amenable to primary or secondary closure, the conventional standard of care (SoC) treatment for these wound types is split-thickness skin grafting (STSG). This invasive procedure requires adequate availability of donor skin and is associated with donor site morbidity, high healthcare resource use (HCRU), and costs related to prolonged hospitalization. As such, treatment options that can facilitate effective healing and donor skin sparing have been highly anticipated. The RECELL® Autologous Cell Harvesting Device facilitates preparation of an autologous skin cell suspension (ASCS) for the treatment of acute thermal burns and FT skin defects. In initial clinical trials, the approach showed superior donor skin-sparing benefits and comparable wound healing to SoC STSG among patients with acute thermal burn injuries. These findings led to approval of RECELL for this indication by the US Food and Drug Administration (FDA) in 2018. Subsequent clinical evaluation in non-thermal FT skin wounds showed that RECELL, when used in combination with widely meshed STSG, provides donor skin-sparing advantages and comparable healing outcomes compared with SoC STSG. As a result, the device received FDA approval in June of 2023 for treatment of FT skin defects caused by traumatic avulsion or surgical excision or resection. Given that health economic advantages have been demonstrated for RECELL ± STSG versus STSG alone when used for burn therapy, it is prudent to examine similarities in the burn and FT skin defect treatment pathways to forecast the potential health economic advantages for RECELL when used in FT skin defects. This article discusses the parallels between the two indications, the clinical outcomes reported for RECELL, and the HCRU and cost benefits that may be anticipated with use of the device for non-thermal FT skin defects.
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Project description:BackgroundThe radial forearm free flap (RFFF) serves as a workhorse for a variety of reconstructions. Although there are a variety of surgical techniques for donor site closure after RFFF raising, the most common techniques are closure using a split-thickness skin graft (STSG) or a full-thickness skin graft (FTSG). The closure can result in wound complications and function and aesthetic compromise of the forearm and hand. The aim of the planned systematic review and meta-analysis is to compare the wound-related, function-related and aesthetics-related outcome associated with full-thickness skin grafts (FTSG) and split-thickness skin grafts (STSG) in radial forearm free flap (RFFF) donor site closure.MethodsA systematic review and meta-analysis will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be followed. Electronic databases and platforms (PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI)) and clinical trial registries (ClinicalTrials.gov, the German Clinical Trials Register, the ISRCTN registry, the International Clinical Trials Registry Platform) will be searched using predefined search terms until 15 January 2024. A rerun of the search will be carried out within 12 months before publication of the review. Eligible studies should report on the occurrence of donor site complications after raising an RFFF and closure of the defect. Included closure techniques are techniques that use full-thickness skin grafts and split-thickness skin grafts. Excluded techniques for closure are primary wound closure without the use of skin graft. Outcomes are considered wound-, functional-, and aesthetics-related. Studies that will be included are randomized controlled trials (RCTs) and prospective and retrospective comparative cohort studies. Case-control studies, studies without a control group, animal studies and cadaveric studies will be excluded. Screening will be performed in a blinded fashion by two reviewers per study. A third reviewer resolves discrepancies. The risk of bias in the original studies will be assessed using the ROBINS-I and RoB 2 tools. Data synthesis will be done using Review Manager (RevMan) 5.4.1. If appropriate, a meta-analysis will be conducted. Between-study variability will be assessed using the I2 index. If necessary, R will be used. The quality of evidence for outcomes will eventually be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.DiscussionThis study's findings may help us understand both closure techniques' complication rates and may have important implications for developing future guidelines for RFFF donor site management. If available data is limited and several questions remain unanswered, additional comparative studies will be needed.Systematic review registrationThe protocol was developed in line with the PRISMA-P extension for protocols and was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 17 September 2023 (registration number CRD42023351903).
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Project description:Physicians have observed that surgical wounds in the elderly heal with thinner scars than wounds in young patients. Understanding this phenomenon may reveal strategies for promoting scarless wound repair. We show that full-thickness skin wounds in aged but not young mice fully regenerate. Exposure of aged animals to blood from young mice by parabiosis counteracts this regenerative capacity. The secreted factor, stromal-derived factor 1 (SDF1), is expressed at higher levels in wounded skin of young mice. Genetic deletion of SDF1 in young skin enhanced tissue regeneration. In aged mice, enhancer of zeste homolog 2 (EZH2) and histone H3 lysine 27 trimethylation are recruited to the SDF1 promoter at higher levels, and pharmacologic inhibition of EZH2 restores SDF1 induction and prevents tissue regeneration. Similar age-dependent EZH2-mediated SDF1 suppression occurs in human skin. Our findings counter the current dogma that tissue function invariably declines with age and suggest new therapeutic strategies in regenerative medicine.
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Project description:Impaired wound healing is an immense medical challenge, and while autologous skin grafting remains the "gold-standard" therapeutic option for repairing wounds that cannot be closed by primary or secondary intention, it is limited by substantial donor site morbidity. We previously developed the alternative approach of harvesting full-thickness skin tissue in the form of "micro skin tissue columns" (MSTCs), without causing scarring or any other long-term morbidity. In this study we investigated how MSTC treatment affects the different cellular processes involved in wound healing. We found that MSTC-derived cells were able to remodel and repopulate the wound volume, and positively impact multiple aspects of the wound healing process, including accelerating re-epithelialization by providing multiple cell sources throughout the wound area, increasing collagen deposition, enhancing dermal remodeling, and attenuating the inflammatory response. These effects combined to enhance both epidermal and dermal wound healing. This MSTC treatment approach was designed for practical clinical use, could convey many benefits of autologous skin grafting, and avoids the major drawback of donor site morbidity.
| S-EPMC7814113 | biostudies-literature
Project description:Clinical application of skin substitute is typically a two-stage procedure with application of skin substitute matrix to the wound followed by engraftment of a split-thickness skin graft (STSG). This two-stage procedure requires multiple interventions, increasing the time until the wound is epithelialised. In this study, the feasibility of a one-stage procedure by combining bioengineered collagen-chondroitin-6-sulfate (DS1) or decellularised fetal bovine skin substitute (DS2) with autologous skin cell suspension (ASCS) in a porcine full-thickness wound healing model was evaluated. Twelve full-thickness excisional wounds on the backs of pigs received one of six different treatments: empty; ASCS; DS1 with or without ASCS; DS2 with or without ASCS. The ASCS was prepared using a point-of-care device and was seeded onto the bottom side of DS1, DS2, and empty wounds at 80 000 cells/cm2 . Wound measurements and photographs were taken on days 0, 9, 14, 21, 28, 35, and 42 post-wounding. Histological analysis was performed on samples obtained on days 9, 14, 28, and 42. Wounds in the empty group or with ASCS alone showed increased wound contraction, fibrosis, and myofibroblast density compared with other treatment groups. The addition of ASCS to DS1 or DS2 resulted in a marked increase in re-epithelialisation of wounds at 14 days, from 15 ± 11% to 71 ± 20% (DS1 vs DS1 + ASCS) or 28 ± 14% to 77 ± 26 (DS2 vs DS2 + ASCS) despite different mechanisms of tissue regeneration employed by the DS used. These results suggest that this approach may be a viable one-stage treatment in clinical practice.
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Project description:The human skin is a significant barrier for protection against pathogen transmission. Rodent models used to investigate human-specific pathogens that target the skin are generated by introducing human skin grafts to immunocompromised rodent strains. Infection-induced immunopathogenesis has been separately studied in humanized rodent models developed with human lymphoid tissue and hematopoietic stem cell transplants. Successful co-engraftment of human skin, autologous lymphoid tissues, and autologous immune cells in a rodent model has not yet been achieved, though it could provide a means of studying the human immune response to infection in the human skin. Here, we introduce the human Skin and Immune System (hSIS)-humanized NOD-scid IL2Rγnull (NSG) mouse and Sprague-Dawley-Rag2tm2hera Il2rγtm1hera (SRG) rat models, co-engrafted with human full-thickness fetal skin, autologous fetal lymphoid tissues, and autologous fetal liver-derived hematopoietic stem cells. hSIS-humanized rodents demonstrate the development of human full-thickness skin, along with autologous lymphoid tissues, and autologous immune cells. These models also support human skin infection following intradermal inoculation with community-associated methicillin-resistant Staphylococcus aureus. The co-engraftment of these human skin and immune system components into a single humanized rodent model could provide a platform for studying human skin infections.
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