Disrupting Mechanotransduction Decreases Fibrosis and Contracture in Porcine Split Thickness Skin Grafting
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE190849 | GEO | 2021/12/16
REPOSITORIES: GEO
Similar Datasets
Project description:Disrupting Mechanotransduction Decreases Fibrosis and Contracture in Porcine Split Thickness Skin Grafting
| PRJNA788620 | ENA
Project description:We quantify the effects of FAK inhibition on three-dimensional (3D) cultured human fibroblasts at the cellular and transcriptomic level using single cell RNA-sequencing. We demonstrate that mechanical stress induces pro-fibrotic fibroblast differentiation fates in large organisms, which can effectively be averted by FAK inhibition, which induces discrete fibroblast clusters that promote wound regeneration.
2021-02-24 | GSE167339 | GEO
Project description:To report our successful outcomes of genital split-thickness skin graft (STSG) in covering major skin loss and providing good functional and cosmetic outcomes.A retrospective chart review was performed for all adult urology patients who underwent STSG at our institution from 1998 to 2014. Patients had a wide range of disease etiologies, including tissue loss (eg post-Fournier's gangrene), lymphedema, buried penis, foreign body injection, and tumors.A total of 54 patients were identified with the following breakdown of etiology: 13 patients with tissue loss (eg post-Fournier's gangrene), 13 with lymphedema, 12 with buried penis, 8 with foreign body injection, 4 with hidradenitis suppurativa, and 4 with tumors. Fifty-two out of 54 patients had more than 90% graft take, with maintained or improved erection, normal voiding, good cosmetic outcome as judged by the patient and the examining surgeon, and normal mobility. One patient died at 3 months due to cardiovascular cause, and 1 patient had a poor take of the graft.We show the wide variety of indications for STSG use, the ease of the technique, and its successful outcomes. We believe this procedure should be offered to patients as a first-line treatment and also as a last resort when other more conservative approaches fail.
| S-EPMC4920551 | biostudies-literature
Project description:BackgroundPatients with nonhealing lower extremity (LE) wounds often require a split-thickness skin graft (STSG) for closure. Nonviable tissue must be debrided before STSG inset. Our study aimed to compare differences in debridement depth on STSG outcomes.MethodsChronic, atraumatic LE wounds receiving STSG from December 2014 to December 2022 at a single institution were reviewed. Demographics, wound characteristics, operative details, and outcomes were collected. Superficially debrided wounds were compared with wounds receiving deep debridement (DD), defined by debriding to the level of white tissue underlying the granulation tissue. Subanalysis was performed on wounds that had a negative and positive postdebridement culture. Primary outcome was graft failure.ResultsOverall, 244 wounds in 168 patients were identified. In total, 158 (64.8%) wounds were superficially debrided and 86 (35.3%) received DD. The cohort had a median Charlson Comorbidity Index of 4 [interquartile range (IQR): 3]. Diabetes (56.6%) and peripheral artery disease (36.9%) were prevalent. The only statically significant demographic difference between groups was congestive heart failure (SD: 14.9% versus DD: 3.0%, P = 0.017). Wound size, depth, and all microbiology results were similar between groups. Postoperatively, the DD group demonstrated significantly less graft failure (10.5% versus 22.2%, P = 0.023). In a multivariate regression, DD was independently associated with lower odds of graft failure (OR: 0.0; CI, 0.0-0.8; P = 0.034). Sub-analysis of graft failure supported this finding in culture-positive wounds (DD: 7.6% versus DD: 22.1%, P = 0.018) but not in culture-negative wounds (13.6% versus 22.2%, P = 0.507).ConclusionsThe DD technique demonstrates improved outcomes in chronic, culture-positive LE wounds receiving STSG.
| S-EPMC11319320 | biostudies-literature
Project description:BackgroundSplit-thickness skin grafting (SSG) is an important modality for wound closure. However, the donor site becomes a second, often painful wound, which may take more time to heal than the graft site itself and holds the risk of infection and scarring. Epidermal grafting (EG) is an alternative method of autologous skin grafting that harvests only the epidermal layer of the skin by applying continuous negative pressure on the normal skin to raise blisters. This procedure has minimal donor site morbidity and is relatively pain-free, allowing autologous skin grafting in an outpatient setting. We plan to compare EG to SSG and to further investigate the cellular mechanism by which each technique achieves wound healing.Methods/designEPIGRAAFT is a multicentre, randomised, controlled trial that compares the efficacy and wound-healing mechanism of EG with SSG for wound healing. The primary outcome measures are the proportion of wounds healed in 6 weeks and the donor site healing time. The secondary outcome measures include the mean time for complete wound healing, pain score, patient satisfaction, health care utilisation, cost analysis, and incidence of adverse events.DiscussionThis study is expected to define the efficacy of EG and promote further understanding of the mechanism of wound healing by EG compared to SSG. The results of this study can be used to inform the current best practise for wound care.Trial registrationClinicaltrials.gov identifier, NCT02535481 . Registered on 11 August 2015.
| S-EPMC4869340 | biostudies-literature
Project description:BackgroundSplit-thickness skin grafting (STSG) is a frequently used reconstructive technique, and its donor site represents a standardized clinical model to evaluate wound dressings. We compared hydroactive nanocellulose-based, silver-impregnated and ibuprofen-containing foam wound dressings.MethodsA total of 46 patients scheduled for elective surgery were evaluated on the STSG donor site for wound healing (time-to-healing, Hollander Wound Evaluation Scale), pain level (Visual Analogue Scale), and handling (ease of use), as well as scar quality (Patient Scar Assessment Scale, Vancouver Scar Scale) after 3, 6 and 12 months.ResultsAlmost all dressings compared equally well. We observed statistically relevant differences for pain level favoring the ibuprofen-containing dressing (p = 0.002, ΔAIC = 8.1), and user friendliness in favor of nanocellulose (dressing removal: p = 0.037, ΔAIC = 2.59; application on patient: p = 0.042, ΔAIC = 2.33; wound adhesion: p = 0.017, ΔAIC = 4.16; sensation on skin: p = 0.027, ΔAIC = 3.21). We did not observe any differences for wound healing across all groups. Treatment with hydroactive nanocellulose and the ibuprofen-containing foam revealed statistically relevant better scar appearances as compared to the silver wound dressing (p < 0.001, ΔAIC = 14.77).ConclusionAll wound dressings performed equally well, with the detected statistical differences hinting future directions of clinical relevance. These include the reserved use of silver containing dressings for contaminated or close to contaminated wounds, and the facilitated clinical application of the nanocellulose dressing, which was the only suitable candidate in this series to be impregnated with a range of additional therapeutic agents (e.g., disinfectants and pain-modulating drugs). Personalized donor site management with the tested dressings can meet individual clinical requirements after STSG and improve management strategies and ultimately patient outcomes.
| S-EPMC9506097 | biostudies-literature
Project description:Endothelial cell (EC) attachment to the matrix and adjacent cells generates a mechanical environment that maintains a restrictive barrier against the uncontrolled influx of circulating protein and immune cells. Mechanisms that mediate the transition from restrictive to leaky endothelium, a hallmark of tissue injury exemplified by acute lung injury (ALI), remain elusive. Here, we show that FAK sensing and transmission of mechanical tension to the EC nucleus governs cell fate. In FAK-deleted EC, increased EC tension activated DNMT3a, which induced methylation of the KLF2 promoter leading to impaired synthesis of KLF2 and restrictive EC transcriptome, including S1PR1. FAK suppressed DNMT3a activity by restricting the tyrosine phosphorylation of nuclear envelope protein, emerin at Y74/Y95, and its localization in a nuclear cap. Inhibiting emerin phosphorylation or DNMT3a activity in damaged lungs enabled KLF2 transcription of S1PR1, rescuing the restrictive EC phenotype. Our works reveal a paradigm whereby FAK sensing of tension transmission to the nucleus maintains restrictive EC transcriptome and lung homeostasis.
2022-08-28 | GSE212037 | GEO
Project description:Mechanical cues activate cardiac fibroblasts and induce differentiation into myofibroblasts, which are key steps for development of cardiac fibrosis. In vitro, the high stiffness of plastic culturing conditions will also induce these changes. It is therefore challenging to study resting cardiac fibroblasts and their activation in vitro. Here we investigate the extent to which disrupting mechanotransduction by culturing cardiac fibroblasts on soft hydrogels or in the presence of biochemical inhibitors can be used to maintain resting cardiac fibroblasts in vitro. Primary cardiac fibroblasts were isolated from adult mice and cultured on plastic or soft (4.5 kPa) polyacrylamide hydrogels. Myofibroblast marker gene expression and smooth muscle α-actin (SMA) fibers were quantified by real-time PCR and immunostaining, respectively. Myofibroblast differentiation was prevented on soft hydrogels for 9 days, but had occurred after 15 days on hydrogels. Transferring myofibroblasts to soft hydrogels reduced expression of myofibroblast-associated genes, albeit SMA fibers remained present. Inhibitors of transforming growth factor β receptor I (TGFβRI) and Rho-associated protein kinase (ROCK) were effective in preventing and reversing myofibroblast gene expression. SMA fibers were also reduced by blocker treatment although cell morphology did not change. Reversed cardiac fibroblasts maintained the ability to re-differentiate after the removal of blockers, suggesting that these are functionally similar to resting cardiac fibroblasts. However, actin alpha 2 smooth muscle (Acta2), lysyl oxidase (Lox) and periostin (Postn) were no longer sensitive to substrate stiffness, suggesting that transient treatment with mechanotransduction inhibitors changes the mechanosensitivity of some fibrosis-related genes. In summary, our results bring novel insight regarding the relative importance of specific mechanical signaling pathways in regulating different myofibroblast-associated genes. Furthermore, combining blocker treatment with the use of soft hydrogels has not been tested previously and revealed that only some genes remain mechano-sensitive after phenotypic reversion. This is important information for researchers using inhibitors to maintain a "resting" cardiac fibroblast phenotype in vitro as well as for our current understanding of mechanosensitive gene regulation.
| S-EPMC7588109 | biostudies-literature
Project description:Mechanical forces generated through adhesive interaction of endothelial cells (EC) influence nuclear envelope and thereby gene transcription. Alteration in EC mechanical forces may trigger aberrant gene transcription leading to lethal vascular diseases including acute lung injury (ALI). The intrinsic pathways that instruct EC nuclear-mechanotransduction and thereby maintains vascular homeostasis remain elusive. We have identified focal adhesion kinase (FAK)-mediated mechanotransduction at the nuclear envelope in instructing transcription of EC-barrier protective genes. We show that loss of EC-FAK increases intracellular tension, which in turn activates nuclear envelop protein emerin, and DNA methyltransferase 3a (DNMT3a). Methylation of transcription factor KLF2 promoter by DNMT3a impaired KLF2 synthesis and transcription of the crucial barrier-maintaining gene, S1PR1. Restoring KLF2 or S1PR1 expression or impairing emerin or DNMT3a activity rescued vascular homeostasis in lungs with FAK-deficient or WT-damaged endothelium. Thus, FAK protects against tension-induced aberrant DNA methylation in EC and is a promising target to prevent ALI.
2022-07-11 | GSE207789 | GEO