scholarly journals The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

2018 ◽  
Vol 51 (2) ◽  
pp. 647-663 ◽  
Author(s):  
Bobin Mi ◽  
Jing Liu ◽  
Yi Liu ◽  
Liangcong Hu ◽  
Yukun Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Wound Healing ◽  
Antimicrobial Peptide ◽  
Structural Stability ◽  
Cell Counting ◽  
Sprague Dawley ◽  
Skin Wound Healing ◽  
High Sodium

Background/Aims: Antimicrobial peptides are effective promoters of wound healing but are susceptible to degradation. In this study, we replaced the GIGDP unit on the N-terminal of the endogenous human antimicrobial peptide hBD-2 with APKAM to produce A-hBD-2 and analyzed the effect on wound healing both in vitro and in vivo. Methods: The effects of A-hBD-2 and hBD-2 on cytotoxicity and proliferation in keratinocytes were assessed by Cell Counting Kit-8 assay. The structural stability and antimicrobial activity of hBD-2 and A-hBD-2 were evaluated against Staphylococcus aureus. RNA and proteins levels were evaluated by real-time PCR and western blotting, respectively. Cell migration was evaluated using a transwell assay. Cell cycle analysis was performed by flow cytometry. Wound healing was assessed in Sprague-Dawley rats. Epidermal thickness was evaluated by hematoxylin and eosin staining. Results: We found that hBD-2 exhibited cytotoxicity at high concentrations and decreased the structural stability in the presence of high sodium chloride concentrations. A-hBD-2 exhibited increased structural stability and antimicrobial activity, and had lower cytotoxicity in keratinocytes. A-hBD-2 increased the migration and proliferation of keratinocytes via phosphorylation of EGFR and STAT3 and suppressed terminal differentiation of keratinocytes. We also found that A-hBD-2 elicited mobilization of intracellular Ca2+ and stimulated keratinocytes to produce pro- and anti-inflammatory cytokines and chemokines via phospholipase C activation. Furthermore, A-hBD-2 promoted wound healing in vivo. Conclusion: Our data suggest that A-hBD-2 may be a promising candidate therapy for wound healing.

scholarly journals Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Closure ◽  
Expression Patterns ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Specific Expression ◽  
Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models

2021 ◽  
pp. 153473462110021
Author(s):  
Joon M. Jung ◽  
Hae K. Yoon ◽  
Chang J. Jung ◽  
Soo Y. Jo ◽  
Sang G. Hwang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Plasma Treatment ◽  
Cold Plasma ◽  
Smooth Muscle Actin ◽  
Treated Group ◽  
Control Group ◽  
Alpha Smooth Muscle Actin ◽  
Skin Wound Healing

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

scholarly journals Systemic and topical administration of spermidine accelerates skin wound healing

2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Wound Repair ◽  
Healing Process ◽  
Topical Administration ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

Different Trypanosoma cruzi calreticulin domains mediate migration and proliferation of fibroblasts in vitro and skin wound healing in vivo

2018 ◽  
Vol 310 (8) ◽  
pp. 639-650 ◽  
Author(s):  
Jose Ignacio Arias ◽  
Natalia Parra ◽  
Carolina Beato ◽  
Cristian Gabriel Torres ◽  
Christopher Hamilton-West ◽  
...  
Keyword(s):  
Wound Healing ◽  
Trypanosoma Cruzi ◽  
Skin Wound ◽  
Skin Wound Healing

scholarly journals Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

2020 ◽  
Vol 8 ◽  
Author(s):  
Pengcheng Xu ◽  
Yaguang Wu ◽  
Lina Zhou ◽  
Zengjun Yang ◽  
Xiaorong Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Platelet Rich Plasma ◽  
Skin Wound ◽  
Local Inflammation ◽  
Skin Wound Healing

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

scholarly journals Film Dressings Based on Hydrogels: Simultaneous and Sustained-Release of Bioactive Compounds with Wound Healing Properties

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 447 ◽  
Author(s):  
Fabian Ávila-Salas ◽  
Adolfo Marican ◽  
Soledad Pinochet ◽  
Gustavo Carreño ◽  
Oscar Valdés ◽  
...  
Keyword(s):  
Wound Healing ◽  
Sustained Release ◽  
Bioactive Compounds ◽  
Target Therapy ◽  
Dicarboxylic Acids ◽  
Skin Wound ◽  
Dynamics Simulation ◽  
Skin Wound Healing

This research proposes the rational modeling, synthesis and evaluation of film dressing hydrogels based on polyvinyl alcohol crosslinked with 20 different kinds of dicarboxylic acids. These formulations would allow the sustained release of simultaneous bioactive compounds including allantoin, resveratrol, dexpanthenol and caffeic acid as a multi-target therapy in wound healing. Interaction energy calculations and molecular dynamics simulation studies allowed evaluating the intermolecular affinity of the above bioactive compounds by hydrogels crosslinked with the different dicarboxylic acids. According to the computational results, the hydrogels crosslinked with succinic, aspartic, maleic and malic acids were selected as the best candidates to be synthesized and evaluated experimentally. These four crosslinked hydrogels were prepared and characterized by FTIR, mechanical properties, SEM and equilibrium swelling ratio. The sustained release of the bioactive compounds from the film dressing was investigated in vitro and in vivo. The in vitro results indicate a good release profile for all four analyzed bioactive compounds. More importantly, in vivo experiments suggest that prepared formulations could considerably accelerate the healing rate of artificial wounds in rats. The histological studies show that these formulations help to successfully reconstruct and thicken epidermis during 14 days of wound healing. Moreover, the four film dressings developed and exhibited excellent biocompatibility. In conclusion, the novel film dressings based on hydrogels rationally designed with combinatorial and sustained release therapy could have significant promise as dressing materials for skin wound healing.

222. A new role for activin in endometrial restoration after menses

2008 ◽  
Vol 20 (9) ◽  
pp. 22
Author(s):  
T. J. Kaitu'u-Lino ◽  
D. J. Phillips ◽  
N. B. Morison ◽  
L. A. Salamonsen
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Abnormal Uterine Bleeding ◽  
Positive Control ◽  
Activin A ◽  
In Vivo Studies ◽  
Skin Wound Healing ◽  
Complete Repair

10% of Australian women suffer from abnormal uterine bleeding (AUB). To stop endometrial bleeding after menstruation, the endometrium must repair adequately. We propose that endometrial restoration after menstruation has characteristics of wound healing and that inadequate endometrial repair may result in AUB. In vivo studies support a contribution of activins to skin wound healing: in mice overexpressing activins' natural inhibitor, follistatin, wound healing is significantly delayed (1). We hypothesised that activin would enhance endometrial repair and examined its contribution using an in vitro wound healing model and our well characterised in vivo mouse model of endometrial breakdown and repair (2). For the in vitro model, confluent human endometrial epithelial cells (ECC-1 cell line) were wounded and treated with carrier protein (control, 0.1% BSA), activin A (50ng/mL) or EGF (positive control: 50ng/mL). Wound areas were quantitated daily for 6 days. For the in vivo study, serum follistatin levels were measured by ELISA in follistatin overexpressing mice (FS) (2) and wild-type (WT) littermates. Mice were induced to undergo endometrial breakdown and repair (mimicking menstruation in women). Activin βA was immunolocalised during endometrial repair, and extent of repair assessed using our morphological scoring system (2). ECC-1 wound repair was significantly (P < 0.05) enhanced by activin A treatment v. control from days 2–6 of culture. In WT mice, activin βA localised to areas of endometrial repair. Serum follistatin was significantly elevated in FS mice v. controls (33.3 ± 3.8 v 7.07 ± 1.8 ng/mL, P < 0.01). In FS mice (n = 8) only 50% of uterine sections showed complete repair after endometrial breakdown, significantly less than those from WT animals (n = 15, P < 0.05) where 85% of sections demonstrated complete repair. These results demonstrate for the first time that activin A functions to promote endometrial restoration following menses and that this can be delayed under physiological conditions: such studies indicate potential treatments for AUB. (1) Wankell et al. (2001) EMBO J 20:5361–5372 (2) Kaitu'u-Lino et al. (2007) Endocrinology 148:5105–5111

scholarly journals Gelatin-Based Hybrid Scaffolds: Promising Wound Dressings

Polymers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 2959 ◽  
Author(s):  
Sindi P. Ndlovu ◽  
Kwanele Ngece ◽  
Sibusiso Alven ◽  
Blessing A. Aderibigbe
Keyword(s):  
Mechanical Properties ◽  
Antimicrobial Activity ◽  
Wound Healing ◽  
Antimicrobial Agents ◽  
Healing Process ◽  
Wound Dressings ◽  
Wound Healing Process ◽  
Delayed Wound Healing

Wound care is a major biomedical field that is challenging due to the delayed wound healing process. Some factors are responsible for delayed wound healing such as malnutrition, poor oxygen flow, smoking, diseases (such as diabetes and cancer), microbial infections, etc. The currently used wound dressings suffer from various limitations, including poor antimicrobial activity, etc. Wound dressings that are formulated from biopolymers (e.g., cellulose, chitin, gelatin, chitosan, etc.) demonstrate interesting properties, such as good biocompatibility, non-toxicity, biodegradability, and attractive antimicrobial activity. Although biopolymer-based wound dressings display the aforementioned excellent features, they possess poor mechanical properties. Gelatin, a biopolymer has excellent biocompatibility, hemostatic property, reduced cytotoxicity, low antigenicity, and promotes cellular attachment and growth. However, it suffers from poor mechanical properties and antimicrobial activity. It is crosslinked with other polymers to enhance its mechanical properties. Furthermore, the incorporation of antimicrobial agents into gelatin-based wound dressings enhance their antimicrobial activity in vitro and in vivo. This review is focused on the development of hybrid wound dressings from a combination of gelatin and other polymers with good biological, mechanical, and physicochemical features which are appropriate for ideal wound dressings. Gelatin-based wound dressings are promising scaffolds for the treatment of infected, exuding, and bleeding wounds. This review article reports gelatin-based wound dressings which were developed between 2016 and 2021.

scholarly journals Overview of Cold Atmospheric Plasma in Wounds Treatment

2020 ◽  
Vol 5 (10) ◽  
Keyword(s):  
Wound Healing ◽  
Skin Wound ◽  
Atmospheric Plasma ◽  
Active Components ◽  
Negative Effects ◽  
Skin Wound Healing ◽  
Cold Atmospheric Plasma ◽  
In Vivo Experiments

Cold atmospheric plasma (CAP), a room temperate ionised gas, known as the fourth state of matter is an ionised gas and can be produced from argon, helium, nitrogen, oxygen or air at atmospheric pressure and low temperatures. CAP has become a new promising way for many biomedical applications, such as disinfection, cancer treatment, root canal treatment, wound healing, and other medical applications. Among these applications, investigations of plasma for skin wound healing have gained huge success both in vitro and in vivo experiments without any known significant negative effects on healthy tissues. The development of CAP devices has led to novel therapeutic strategies in wound healing, tissue regeneration and skin infection management. CAP consists of a mixture of multitude of active components such as charged particles, electric field, UV radiation, and reactive gas species which can act synergistically. CAP has lately been recognized as an alternative approach in medicine for sterilization of wounds by its antiseptic effects and promotion of wound healing by stimulation of cell proliferation and migration of wound related skin cells. With respect to CAP applications in medicine, this review focuses particularly on the potential of CAP and the known molecular basis for this action. We summarize the available literature on the plasma devices developed for wound healing, the current in vivo and in vitro use of CAP, and the mechanism behind it as well as the biosafety issues.

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