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Project description:Hypertrophic scars arise from dysregulated wound healing under prolonged mechanical tension, causing disfiguring fibrosis. However, limited preclinical models replicate key features of human tension-induced scarring. We developed an innovative murine model utilizing suture anchoring to impose persistent transverse-axial stretch across healing incisions, mimicking excessive wound tension that leads to hypertrophy clinically. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage while leaving wound edges on the lower back relaxed. This localized anchoring restrained wound contraction, maintaining high tension throughout remodeling analogous to scars widening under stress. Stretched upper wounds developed profound fibrotic changes compared to relaxed controls. Scars induced by suture-anchored tension displayed macroscopic hypertrophy, hardness, erythema, and pruritis up to 3 months. Histologically, scars induced by suture-anchored tension were hypercellular, hypervascular, hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. MiRNA sequencing revealed the different signature in suture-anchored tension induced hypertrophic scars compared to control normal scars.
2023-09-28 | GSE243948 | GEO
Project description:Hypertrophic scars arise from dysregulated wound healing under prolonged mechanical tension, causing disfiguring fibrosis. However, limited preclinical models replicate key features of human tension-induced scarring. We developed an innovative murine model utilizing suture anchoring to impose persistent transverse-axial stretch across healing incisions, mimicking excessive wound tension that leads to hypertrophy clinically. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage while leaving wound edges on the lower back relaxed. This localized anchoring restrained wound contraction, maintaining high tension throughout remodeling analogous to scars widening under stress. Stretched upper wounds developed profound fibrotic changes compared to relaxed controls. Scars induced by suture-anchored tension displayed macroscopic hypertrophy, hardness, erythema, and pruritis up to 3 months. Histologically, scars induced by suture-anchored tension were hypercellular, hypervascular, hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. MRNA sequencing revealed the fibrogenic signature in suture-anchored tension induced hypertrophic scars, which exhibited transcriptional overlap with mechanically-stretched scars, human hypertrophic and keloid scars.
2023-09-28 | GSE243949 | GEO
Project description:Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model
| PRJNA1020782 | ENA
Project description:Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model [miRNA]
| PRJNA1020784 | ENA
Project description:Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model [RNA-Seq]
| PRJNA1020785 | ENA
Project description:Hypertrophic scars (HTS) and keloids are forms of aberrant cutaneous healing with excessive extracellular matrix (ECM) deposition. Current therapies still fall short and cause undesired effects. We aimed to thoroughly evaluate the ability of growth hormone releasing peptide 6 (GHRP6) to both prevent and reverse cutaneous fibrosis and to acquire the earliest proteome data supporting GHRP6's acute impact on aesthetic wound healing. Two independent sets of experiments addressing prevention and reversion effects were conducted on the classic HTS model in rabbits. In the prevention approach, the wounds were assigned to topically receive GHRP6, triamcinolone acetonide (TA), or vehicle (1% sodium carboxy methylcellulose [CMC]) from day 1 to day 30 post-wounding. The reversion scheme was based on the infiltration of either GHRP6 or sterile saline in mature HTS for 4 consecutive weeks. The incidence and appearance of HTS were systematically monitored. The sub-epidermal fibrotic core area of HTS was ultrasonographically determined, and the scar elevation index was calculated on haematoxylin/eosin-stained, microscopic digitised images. Tissue samples were collected for proteomics after 1 hour of HTS induction and treatment with either GHRP6 or vehicle. GHRP6 prevented the onset of HTS without the untoward reactions induced by the first-line treatment triamcinolone acetonide (TA); however, it failed to significantly reverse mature HTS. The preliminary proteomic study suggests that the anti-fibrotic preventing effect exerted by GHRP6 depends on different pathways involved in lipid metabolism, cytoskeleton arrangements, epidermal cells' differentiation, and ECM dynamics. These results enlighten the potential success of GHRP6 as one of the incoming alternatives for HTS prevention.
| S-EPMC7949743 | biostudies-literature
Project description:IntroductionPatellar inferior pole fractures are challenging to obtain sufficient fixation. The purpose of this retrospective, case-controlled study was to compare the clinical and radiological outcomes between tension band wiring (TBW) and our novel double-row suture anchor (SA) technique in patellar inferior pole fractures.Materials and methodsThis retrospective study included patients who underwent TBW or SA fixation for patellar inferior pole fractures from 2015 to 2019. A total of 63 patients were divided into two groups according to the surgical procedure: the TBW group (n = 35) and the SA fixation group (n = 28). The visual analog scale score, range of motion of the knee, Lysholm score, Kujala patellofemoral score, and patient satisfaction score were evaluated for clinical and functional outcomes. Radiological outcomes included the time to radiological union, loss of reduction, and the Insall-Salvati (IS) ratio.ResultsSignificant improvements in clinical outcomes were observed in both groups with no significant differences. Bone union was achieved in all patients, and there was no significant difference in the time to radiological union and the IS ratio between the two groups. All patients in the TBW group underwent additional surgeries for implant removal. However, none of the patients in the SA group underwent implant removal or experienced skin irritation.ConclusionOur novel double-row SA technique could provide comparable fixation strength and good clinical outcomes, with fewer complications in patellar inferior pole fractures. This novel SA technique is a satisfactory alternative treatment for patellar inferior pole fractures.
| S-EPMC9758291 | biostudies-literature
Project description:Hypertrophic skin scarring following dermal injury causes extreme pain and psychological trauma for patients. Unfortuately, we do not have effective treatments to prevent or reverse skin scarring. Using RNA and ATAC sequencing of mouse and human fibroblasts, we show that JUN expressing fibroblasts are responsible for skin scarring by regulating CD36 expression. In summary, we show that CD36 antagonism by represent a therapeutic target to overcome JUN hypertrophic skin scarring.
2021-06-22 | GSE178562 | GEO
Project description:Double-row suture-bridge technique for rotator cuff repair has been used for rotator cuff tears. In large tears that require 2 or more lateral row anchors, loosening of the suture bridges could occur because of tightening sequence. By retightening suture limbs before deploying the first lateral row anchor, premature loosening could be prevented and enhance the tension of the construct.
| S-EPMC8556532 | biostudies-literature
Project description:Significance: Cutaneous scarring affects millions of patients worldwide and results in significant financial and psychosocial burdens. Given the immune system's intricate involvement in the initiation and progression of wound healing, it is no surprise that the scarring outcome can be affected by the actions of various immune cells and the cytokines and growth factors they produce. Understanding the role of T cells in regulating immune responses and directing the action of wound mesenchymal cells is essential to developing antifibrotic therapies to reduce the burden of scarring. Recent Advances: As the immune system is intimately involved in wound healing, much work has examined the impact of T cells and their cytokines on the final wound outcome. New innovative tools for studying T cells have resulted in more sophisticated immunophenotyping capabilities and the ability to examine effects of individual cytokines in the wound environment. Critical Issues: Despite continued advances in the study of specific immune cells and their effects on dermal fibrosis, minimal progress has been made to modulate immune responses to result in improved wound cosmesis. Future Directions: The actions of T cells represent potential pharmacologic targets that could lead to novel bioengineered or immunoengineered therapies to improve the lives of people with cutaneous scarring.
| S-EPMC8742284 | biostudies-literature