Skin substitutes for the treatment of chronic wounds in patients with cancer: A retrospective case series.
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ABSTRACT:
SUBMITTER: Stoll JR
PROVIDER: S-EPMC8485225 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Skin substitutes for the treatment of chronic wounds in patients with cancer: A retrospective case series.
Stoll Joseph R JR Noor Sarah J SJ Dusza Stephen W SW Markova Alina A
Journal of the American Academy of Dermatology 20201028 5
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Project description:With the global prevalence of type 2 diabetes mellitus steeply rising, instances of chronic, hard-healing, or non-healing diabetic wounds and ulcers are predicted to increase. The growing understanding of healing and regenerative mechanisms has elucidated critical regulators of this process, including key cellular and humoral components. Despite this, the management and successful treatment of diabetic wounds represents a significant therapeutic challenge. To this end, the development of novel therapies and biological dressings has gained increased interest. Here we review key differences between normal and chronic non-healing diabetic wounds, and elaborate on recent advances in wound healing treatments with a particular focus on biological dressings and their effect on key wound healing pathways.
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Project description:An autologous homologous skin construct (AHSC) has been developed for the repair and replacement of skin. It is created from a small, full-thickness harvest of healthy skin, which contains endogenous regenerative populations involved in native skin repair. A multicenter retrospective review of 15 wounds in 15 patients treated with AHSC was performed to evaluate the hypothesis that a single application could result in wound closure in a variety of wound types and that the resulting tissue would resemble native skin. Patients and wounds were selected and managed per provider's discretion with no predefined inclusion, exclusion, or follow-up criteria. Dressings were changed weekly. Graft take and wound closure were documented during follow-up visits and imaged with a digital camera. Wound etiologies included 5 acute and chronic burn, 4 acute traumatic, and 6 chronic wounds. All wounds were closed with a single application of AHSC manufactured from a single tissue harvest. Median wound, harvest, and defect-to-harvest size ratio were 120 cm2 (range, 27-4800 cm2), 14 cm2 (range, 3-20 cm2), and 11:1 (range, 2:1-343:1), respectively. No adverse reactions with the full-thickness harvest site or the AHSC treatment site were reported. Average follow-up was 4 ± 3 months. An AHSC-treated area was biopsied, and a micrograph of the area was developed using immunofluorescent confocal microscopy, which demonstrated mature, full-thickness skin with nascent hair follicles and glands. This early clinical experience with ASHC suggests that it can close different wound types; however, additional studies are needed to verify this statement.
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Project description:Skin wound healing is a crucial process for regenerating healthy skin and avoiding the undesired consequences associated with open skin wounds. For epidermolysis bullosa (EB), a debilitating group of fragile skin disorders currently without a cure, skin blistering can often be severe and heal poorly, increasing susceptibility to life-threatening complications. To prevent these, investigational therapies have been exploring the use of tissue-engineered skin substitutes (TESSs) aimed at replacing damaged skin and promoting long-term wound closure. These products have either been developed in house or commercially sourced and are composed of allogeneic or autologous human skin cells, often with some form of bioscaffolding. They can be broadly classified based on their cellular composition: keratinocytes (epidermal substitutes), fibroblasts (dermal substitutes) or a combination of both (composite substitutes). Encouraging long-term wound healing has been achieved with epidermal substitutes. However, these substitutes have not demonstrated the same efficacy for all patients, which may be due to the molecular heterogeneity observed between EB subtypes. Autologous composite TESSs, which more closely resemble native human skin, are therefore being investigated and may hold promise for treating an extended range of patients. Additionally, future TESSs for EB are focused on using gene-corrected patient skin cells, which have already demonstrated remarkable long-term wound healing capabilities. In this review, we provide an overview of the different TESSs that have been investigated in clinical studies to treat patients with EB, as well as their long-term wound healing results. Where available, we describe the methods used to develop these products to inform future efforts in this field.
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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 formation of severe scars still represents the result of the closure process of extended and deep skin wounds. To address this issue, different bioengineered skin substitutes have been developed but a general consensus regarding their effectiveness has not been achieved yet. It will be shown that bioengineered skin substitutes, although representing a valid alternative to autografting, induce skin cells in repairing the wound rather than guiding a regeneration process. Repaired skin differs from regenerated skin, showing high contracture, loss of sensitivity, impaired pigmentation and absence of cutaneous adnexa (i.e., hair follicles and sweat glands). This leads to significant mobility and aesthetic concerns, making the development of more effective bioengineered skin models a current need. The objective of this review is to determine the limitations of either commercially available or investigational bioengineered skin substitutes and how advanced skin tissue engineering strategies can be improved in order to completely restore skin functions after severe wounds.
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Project description:Wound healing is a complex physiological process including overlapping phases (hemostatic/inflammatory, proliferating and remodeling phases). Every alteration in this mechanism might lead to pathological conditions of different medical relevance. Treatments for chronic non-healing wounds are expensive because reiterative treatments are needed. Regenerative medicine and in particular mesenchymal stem cells approach is emerging as new potential clinical application in wound healing. In the past decades, advance in the understanding of molecular mechanisms underlying wound healing process has led to extensive topical administration of growth factors as part of wound care. Currently, no definitive treatment is available and the research on optimal wound care depends upon the efficacy and cost-benefit of emerging therapies. Here we provide an overview on the novel approaches through stem cell therapy to improve cutaneous wound healing, with a focus on diabetic wounds and Systemic Sclerosis-associated ulcers, which are particularly challenging. Current and future treatment approaches are discussed with an emphasis on recent advances.
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Project description:Background and aimsAcute-on-chronic liver failure (ACLF) is common in patients with end-stage liver disease and chronic hepatitis B (CHB) or hepatitis B virus- (HBV-) related cirrhosis. To date, no uniform definition and management strategy are available for ACLF. Although a considerable number of studies on ACLF has been published, there are few reports on ACLF in pregnant women with CHB. This study retrospectively reviewed five patients who were diagnosed with ACLF during pregnancy in the past 10 years. We aimed at investigating their clinical characteristics, treatment, biochemical test results, and maternal and fetal outcomes.ResultsAsthenia, anorexia, and jaundice were the main initial clinical manifestations in these patients during the second or third trimester of pregnancy. All patients received antiviral therapy. None of the pregnant women died after treatment. Patient #4 was treated with an artificial liver support system, and patients #2 and #5 underwent transfusion therapy. The acute insult in all patients was HBV DNA reactivation. Except for patient #3, who chose an actively induced vaginal delivery because of intrauterine fetal demise, the remaining four patients underwent a preterm delivery via a cesarean section. The four neonates were alive, although all were small for gestational age.ConclusionAsthenia, anorexia, and jaundice during mid-late pregnancy should be immediately investigated. Before and during the pregnancy, hepatologists or obstetricians should actively screen pregnant women with CHB for HBV DNA status and alanine aminotransferase levels. Reactivation of HBV replication in pregnant women with CHB may lead to ACLF, especially in multiparous women. Once ACLF is diagnosed, antiviral therapy should be considered as soon as possible to protect maternal and fetal health.
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Project description:BackgroundNon-REM parasomnias are not uncommon conditions in the general population. Current treatment options are based on small case series and reports. In this study, we aimed to present the clinical experience from a large cohort of patients.PatientsFive hundred and twelve patients with Non-REM parasomnia or parasomnia overlap disorder (POD), who had undergone a video polysomnography and were exposed to treatment, were retrospectively identified. Treatment outcome was assessed based on patients' reports, and treatment approach on a locally accepted hierarchy of interventions.ResultsForty percent of patients were diagnosed with sleepwalking, 23.8% with mixed-phenotype and 10% with POD. Ultimately, 97.2% reported adequate control of their symptoms. Moreover, 60.1% were treated with pharmacotherapy and 32.0% without, consistent across all phenotypes (p = 0.09). Benzodiazepines were the most common drugs prescribed (47.1%, p < 0.05). In the end, 37.7% of our patients were receiving a benzodiazepine as part of their successful treatment, 11.7% an antidepressant, 9.2% a z-drug, and 10.7% melatonin. Finally, 13.2%, 12.1%, and 5.8% of our patients reported good control of their symptoms with sleep hygiene, management of sleep-disordered breathing, and psychological interventions (cognitive behavioral therapy [CBT] or mindfulness-based stress reduction [MBSR]), as monotherapy, respectively.ConclusionThe treatment approach to effective treatment of the patients with Non-REM parasomnias or POD offering first sleep hygiene advice, next treatment of concurrent sleep disorders and management of other priming factors like stress and anxiety, and lastly pharmacotherapy for Non-REM parasomnia is supported by our results. Non pharmacological interventions were effective in one third of our patients, and CBT/MBSR and melatonin appeared promising new treatments.
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Project description:Engineered skin substitutes (ESS), prepared using primary human fibroblasts and keratinocytes with a biopolymer scaffold, were shown to provide stable closure of excised burns, but relatively little is known about innervation of ESS after grafting. This study investigated innervation of ESS and, specifically, whether Merkel cells are present in healed grafts. Merkel cells are specialized neuroendocrine cells required for fine touch sensation in skin. We discovered cells positive for keratin 20 (KRT20), a general marker for Merkel cells, in the basal epidermis of ESS after transplantation to mice, suggesting the presence of Merkel cells. Cells expressing KRT20 were not observed in ESS in vitro. However, widely separated KRT20-positive cells were observed in basal epidermis of ESS by 2 weeks after grafting. By 4 weeks, these cells increased in number and expressed keratins 18 and 19, additional Merkel cells markers. Putative Merkel cell numbers increased further between weeks 6 and 14; their densities varied widely and no specific pattern of organization was observed, similar to Merkel cell localization in human skin. KRT20-positive cells co-expressed epidermal markers E-cadherin and keratin 15, suggesting derivation from the epidermal lineage, and neuroendocrine markers synaptophysin and chromogranin A, consistent with their identification as Merkel cells. By 4 weeks after grafting, some Merkel cells in engineered skin were associated with immature afferents expressing neurofilament-medium. By 8 weeks, Merkel cells were complexed with more mature neurons expressing neurofilament-heavy. Positive staining for human leukocyte antigen demonstrated that the Merkel cells in ESS were derived from grafted human cells. The results identify, for the first time, Merkel cell-neurite complexes in engineered skin in vivo. This suggests that fine touch sensation may be restored in ESS after grafting, although this must be confirmed with future functional studies.
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Project description:BackgroundSkin is the largest organ in the body and has multiple significant functions. A malformation or injury that compromises its integrity can lead to major issues or even mortality. Wound healing is a vital physiological process of the human skin which facilitates the repair of any damage and the preservation of homeostasis. Possible complications or infections that are fatal may ensue if the patient does not recover within the specified time. Therefore, it is essential to develop biomaterials which facilitate tissue regeneration and exhibit robust biological properties. We conducted a meta-analysis of randomized controlled trials to compare combinations of skin replacements and skin grafts to skin grafts alone for wound treatment, as measured by the Vancouver Scar Scale.MethodsThis meta-analysis utilized various databases, including as PubMed, ProQuest, Web of Science, Science Direct, Scopus, EBSCOhost, and ClinicalTrials.gov, to conduct a comprehensive search for randomized controlled trials that compared the effectiveness of combined skin substitutes and skin grafts to skin grafts alone in the treatment of wounds. The results primarily consisted of scar features assessed using the Vancouver Scar Scale.ResultsMeta-analysis was conducted on a sample of 216 participants from 7 randomized controlled trials. The trials were conducted from 2002 to 2015. The study demonstrated that the use of skin substitutes resulted in a statistically significant improvement in Vancouver Scar Scales ratings compared to skin grafts alone. The mean change was 1.38 (95% CI: 0.13-2.63; p = 0.03).ConclusionThis meta-analysis indicates that the use of skin replacements provides substantial advantages and effectively aids in the closure of wounds. There is no inherent superiority among different skin substitutes. Instead, their suitability for specific patient wound circumstances is the determining factor. A comprehensive and advantageous skin substitute of significant magnitude is needed, rather than relying solely on grafts.
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