Endothelial cell-derived small extracellular vesicles suppress cutaneous wound healing through regulating fibroblasts autophagy

2019 ◽  
Vol 133 (9) ◽  
Author(s):  
Tingting Zeng ◽  
Xiaoyi Wang ◽  
Wei Wang ◽  
Qiling Feng ◽  
Guojuan Lao ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Extracellular Vesicles ◽  
Diabetic Foot ◽  
Collagen Synthesis ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Skin Fibroblasts ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound

Abstract Diabetic foot ulcer is a life-threatening clinical problem in diabetic patients. Endothelial cell-derived small extracellular vesicles (sEVs) are important mediators of intercellular communication in the pathogenesis of several diseases. However, the exact mechanisms of wound healing mediated by endothelial cell-derived sEVs remain unclear. sEVs were isolated from human umbilical vein endothelial cells (HUVECs) pretreated with or without advanced glycation end products (AGEs). The roles of HUVEC-derived sEVs on the biological characteristics of skin fibroblasts were investigated both in vitro and in vivo. We demonstrate that sEVs derived from AGEs-pretreated HUVECs (AGEs-sEVs) could inhibit collagen synthesis by activating autophagy of human skin fibroblasts. Additionally, treatment with AGEs-sEVs could delay the wound healing process in Sprague–Dawley (SD) rats. Further analysis indicated that miR-106b-5p was up-regulated in AGEs-sEVs and importantly, in exudate-derived sEVs from patients with diabetic foot ulcer. Consequently, sEV-mediated uptake of miR-106b-5p in recipient fibroblasts reduces expression of extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in fibroblasts autophagy activation and subsequent collagen degradation. Collectively, our data demonstrate that miR-106b-5p could be enriched in AGEs-sEVs, then decreases collagen synthesis and delays cutaneous wound healing by triggering fibroblasts autophagy through reducing ERK1/2 expression.

scholarly journals Comment on “Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing”

2015 ◽  
Vol 2015 ◽  
pp. 1-3
Author(s):  
Hongling Li ◽  
Cong Cao ◽  
Ai Huang ◽  
Yi Man
Keyword(s):  
Wound Healing ◽  
Potential Role ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Tissue Growth ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Novel Method ◽  
Semiocclusive Dressing ◽  
Experimental Group

A recent paper in this journal, presented a novel method by topical application of growth factors in stimulating diabetic cutaneous wound healing that caught our attention. We believe that the experimental method in the article is efficient and creative, but it also has some controversies and shortcomings to be discussed. We noted that the authors used “Tegaderm” as a semiocclusive dressing film and stated that it exerted a “splinting effect” on the wound margins and controlled contraction. Indeed, the “Tegaderm” itself can serve as a dressing film to isolate the wound bed with outside environments while the “splinting effect” is mainly achieved by adding silicone splints around the wound. Considering the unique properties of silicone splints and “Tegaderm,” our experimental group propose an alternative method named “combined-suturing” technique that is not only suturing the silicone splints but also securing the “Tegaderm” around the wound. The specific reasons and operative procedures are explained in detail in this letter.

scholarly journals The Effects of Silver-Releasing Foam Dressings on Diabetic Foot Ulcer Healing

2021 ◽  
Vol 10 (7) ◽  
pp. 1495
Author(s):  
Yu-Chi Wang ◽  
Hsiao-Chen Lee ◽  
Chien-Lin Chen ◽  
Ming-Chun Kuo ◽  
Savitha Ramachandran ◽  
...  
Keyword(s):  
Wound Healing ◽  
Diabetic Foot ◽  
Healing Rate ◽  
Early Period ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Wound Management ◽  
Control Group ◽  
Diabetic Patients ◽  
High Morbidity

Diabetic foot ulcers (DFUs) are a serious complication in diabetic patients and lead to high morbidity and mortality. Numerous dressings have been developed to facilitate wound healing of DFUs. This study investigated the wound healing efficacy of silver-releasing foam dressings versus silver-containing cream in managing outpatients with DFUs. Sixty patients with Wagner Grade 1 to 2 DFUs were recruited. The treatment group received silver-releasing foam dressing (Biatain® Ag Non-Adhesive Foam dressing; Coloplast, Humlebaek, Denmark). The control group received 1% silver sulfadiazine (SSD) cream. The ulcer area in the silver foam group was significantly reduced compared with that in the SSD group after four weeks of treatment (silver foam group: 76.43 ± 7.41%, SSD group: 27.00 ± 4.95%, p < 0.001). The weekly wound healing rate in the silver foam group was superior to the SSD group during the first three weeks of treatment (p < 0.05). The silver-releasing foam dressing is more effective than SSD in promoting wound healing of DFUs. The effect is more pronounced in the initial three weeks of the treatment. Thus, silver-releasing foam could be an effective wound dressing for DFUs, mainly in the early period of wound management.

In vitro and in vivo Effect of Platelet-Rich Plasma-Based Autologous Topical Serum on Cutaneous Wound Healing

2021 ◽  
pp. 1-13
Author(s):  
Eduardo Anitua ◽  
Victoria Muñoz ◽  
Libe Aspe ◽  
Roberto Tierno ◽  
Adrian García-Salvador ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Damage ◽  
Collagen Synthesis ◽  
Dermal Fibroblast ◽  
Platelet Rich Plasma ◽  
Cell Activity ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Fibroblast Migration ◽  
Edge Contraction

<b><i>Introduction:</i></b> Skin injury and wound healing is an inevitable event during lifetime. However, several complications may hamper the regeneration of the cutaneous tissue and lead to a chronic profile that prolongs patient recovery. Platelet-rich plasma is rising as an effective and safe alternative to the management of wounds. However, this technology presents some limitations such as the need for repeated blood extractions and health-care interventions. <b><i>Objective:</i></b> The aim of this study was to assess the use of an endogenous and storable topical serum (ES) derived from plasma rich in growth factors promoting wound healing, and to obtain preliminary data regarding its clinical and experimental effect over ulcerated skin models and patient care. <b><i>Methods:</i></b> Human dermal fibroblast and 3D organotypic ulcerated skin models were used to assess ES over the main mechanisms of wound healing including cell migration, edge contraction, collagen synthesis, tissue damage, extracellular matrix remodeling, cell death, metabolic activity, and histomorphometry analysis. Additionally, 4 patients suffering from skin wounds were treated and clinically assessed. <b><i>Results:</i></b> ES promoted dermal fibroblast migration, wound edge contraction, and collagen synthesis. When topically applied, ES increased collagen and elastin deposition and reduced tissue damage. The interstitial edema, structural integrity, and cell activity were also maintained, and apoptotic levels were reduced. Patients suffering from hard-to-heal wounds of different etiologies were treated with ES, and the ulcers healed completely within few weeks with no reported adverse events. <b><i>Conclusion:</i></b> This preliminary study suggests that ES might promote cutaneous wound healing and may be useful for accelerating the re-epithelization of skin ulcers.

266-OR: Proteomic Analysis of Diabetic Foot Ulcer Fluid to Identify Biomarkers of Wound Healing: A Prospective Study

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 266-OR
Author(s):  
NASIBEH VATANKHAH ◽  
VAHID JALILI ◽  
YOUNES JAHANGIRI
Keyword(s):  
Wound Healing ◽  
Prospective Study ◽  
Diabetic Foot ◽  
Proteomic Analysis ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
A Prospective Study

scholarly journals Efek Terapi Oksigen Hiperbarik (TOHB) pada Penyembuhan Ulkus Kaki DM Tipe 2 Berdasarkan Skor PEDIS

2019 ◽  
Vol 11 (2) ◽  
pp. 110
Author(s):  
Ekanova R. N. Sumarauw ◽  
Mendy J. Hatibie ◽  
Djony E. Tjandra ◽  
Fredrik G. Langi
Keyword(s):  
Wound Healing ◽  
Diabetic Foot ◽  
Controlled Trial ◽  
Healing Process ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Control Group ◽  
Wound Healing Process ◽  
Holistic Treatment ◽  
The Third

Abstract: Diabetic foot ulcer (DFU) is still a health problem related to the extent amount of time in wound healing process hence increasing the treatment cost. Given any methods that are not sat-isfying, encourage the search of other methods that would increase the wound healing rate, in which hyperbaric oxygen therapy (HBOT) is amongst them. The DFU patient that receives HBOT shows a significant increase in angiogenesis process markedly by faster epithelialization and granulation process. This study was aimed to prove that HBOT could accelerate the wound healing process among DFU patients measured by wound size and depth of PEDIS score. This was a ran-domized controlled trial study, conducted at Surgery Department of Prof. Dr. R. D. Kandou Gen-eral Hospital from September 2018 to March 2019. There were 20 DFU patients divided into two groups, each of 10 patients. The control group received a holistic treatment, meanwhile the HBOT group received a holistic treatment added with the inclusion of HBOT. PEDIS score assessment of DFU in HBOT group was measured before and after the third HBOT session, meanwhile the con-trol group was measured on the first and the third day. The results showed that the difference in PEDIS score value was markedly found in HBOT group compared to the control group (2 vs. 0, P=0.001). Conclusion: HBOT could enhance the wound healing process in DFU patients based on the declined PEDIS score.Keywords: HBOT, PEDIS score, diabetic foot ulcerAbstrak: Ulkus kaki diabetik (UKD) masih merupakan masalah kesehatan terkait proses penyembuhan lama sehingga biaya pengobatan meningkat. Belum adanya metode penanganan yang memuaskan, mendorong pencarian metode percepatan penyembuhan luka, salah satunya ialah terapi oksigen hiperbarik (TOHB). Penderita UKD yang menjalani tambahan TOHB diketahui mengalami peningkatan proses angiogenesis yang menghasilkan proses epitelialisasi dan granulasi yang lebih cepat. Tujuan penelitian ialah untuk membuktikan bahwa TOHB dapat mempercepat proses penyembuhan UKD, dinilai berdasarkan ukuran dan kedalaman luka melalui skor PEDIS. Penelitian ini menggunakan randomized controlled trial dan dilaksanakan di Bagian Bedah RSUP Prof. Dr. R.D. Kandou Manado sejak September 2018 sampai dengan Maret 2019. Subyek penelitian sebanyak 20 penderita UKD, dibagi dalam dua kelompok, masing-masing 10 penderita. Kelompok kontrol menjalani penanganan holistik UKD, sedangkan kelompok TOHB menjalani penanganan holistik UKD dengan TOHB. Penilaian skor PEDIS terhadap UKD pada kelompok TOHB dilakukan sebelum dan sesudah TOHB sesi ke-3, sedangkan pada kelompok kontrol dilakukan penilaian pada hari ke-1 dan hari ke-3 sesudahnya. Hasil penelitian mendapatkan bahwa perubahan skor PEDIS yang terjadi antara kedua pengukuran terlihat lebih besar pada kelompok TOHB dibandingkan kelompok kontrol (2 vs 0, P=0,001). Simpulan. TOHB mempercepat proses penyembuhan UKD dinilai dari penurunan skor PEDIS.Kata kunci: TOHB, skor PEDIS, ulkus kaki diabetik

scholarly journals Atypical Diabetic Foot Ulcer Keratinocyte Protein Signaling Correlates with Impaired Wound Healing

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Glenn D. Hoke ◽  
Corrine Ramos ◽  
Nicholas N. Hoke ◽  
Mary C. Crossland ◽  
Lisa G. Shawler ◽  
...  
Keyword(s):  
Wound Healing ◽  
Signaling Pathways ◽  
Diabetic Foot ◽  
Foot Ulcer ◽  
Predictive Biomarkers ◽  
Diabetic Foot Ulcer ◽  
Study Data ◽  
Protein Signaling ◽  
Impaired Wound Healing ◽  
Signal Transduction Networks

Diabetes mellitus is associated with chronic diabetic foot ulcers (DFUs) and wound infections often resulting in lower extremity amputations. The protein signaling architecture of the mechanisms responsible for impaired DFU healing has not been characterized. In this preliminary clinical study, the intracellular levels of proteins involved in signal transduction networks relevant to wound healing were non-biasedly measured using reverse-phase protein arrays (RPPA) in keratinocytes isolated from DFU wound biopsies. RPPA allows for the simultaneous documentation and assessment of the signaling pathways active in each DFU. Thus, RPPA provides for the accurate mapping of wound healing pathways associated with apoptosis, proliferation, senescence, survival, and angiogenesis. From the study data, we have identified potential diagnostic, or predictive, biomarkers for DFU wound healing derived from the ratios of quantified signaling protein expressions within interconnected pathways. These biomarkers may allow physicians to personalize therapeutic strategies for DFU management on an individual basis based upon the signaling architecture present in each wound. Additionally, we have identified altered, interconnected signaling pathways within DFU keratinocytes that may help guide the development of therapeutics to modulate these dysregulated pathways, many of which parallel the therapeutic targets which are the hallmarks of molecular therapies for treating cancer.

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