Polycaprolactone nanofibers functionalized with placental derived extracellular matrix for stimulating wound healing activity

2018 ◽  
Vol 6 (42) ◽  
pp. 6767-6780 ◽  
Author(s):  
Arun Prabhu Rameshbabu ◽  
Sayanti Datta ◽  
Kamakshi Bankoti ◽  
Elavarasan Subramani ◽  
Koel Chaudhury ◽  
...  

Impaired wound healing is primarily associated with inadequate angiogenesis, repressed cell migration, deficient synthesis of extracellular matrix (ECM) component/growth factors, and altered inflammatory responses in the wound bed environment.

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pawel Olczyk ◽  
Łukasz Mencner ◽  
Katarzyna Komosinska-Vassev

Wound healing is the physiologic response to tissue trauma proceeding as a complex pathway of biochemical reactions and cellular events, secreted growth factors, and cytokines. Extracellular matrix constituents are essential components of the wound repair phenomenon. Firstly, they create a provisional matrix, providing a structural integrity of matrix during each stage of healing process. Secondly, matrix molecules regulate cellular functions, mediate the cell-cell and cell-matrix interactions, and serve as a reservoir and modulator of cytokines and growth factors’ action. Currently known mechanisms, by which extracellular matrix components modulate each stage of the process of soft tissue remodeling after injury, have been discussed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Miho Takahashi ◽  
Yoshie Umehara ◽  
Hainan Yue ◽  
Juan Valentin Trujillo-Paez ◽  
Ge Peng ◽  
...  

In addition to its antimicrobial activity, the skin-derived antimicrobial peptide human β-defensin-3 (hBD-3) promotes keratinocyte proliferation and migration to initiate the wound healing process; however, its effects on fibroblasts, which are the major cell type responsible for wound healing, remain unclear. We investigated the role of hBD-3 in cell migration, proliferation and production of angiogenic growth factors in human fibroblasts and evaluated the in vivo effect of hBD-3 on promoting wound healing and angiogenesis. Following hBD-3 treatment, the mouse wounds healed faster and showed accumulation of neutrophils and macrophages in the early phase of wound healing and reduction of these phagocytes 4 days later. hBD-3-treated wounds also displayed an increased number of fibroblasts and newly formed vessels compared to those of the control mice. Furthermore, the expression of various angiogenic growth factors was increased in the hBD-3-treated wounds. Additionally, in vitro studies demonstrated that hBD-3 enhanced the secretion of angiogenic growth factors such as fibroblast growth factor, platelet-derived growth factor and vascular endothelial growth factor and induced the migration and proliferation of human fibroblasts. The hBD-3-mediated activation of fibroblasts involves the fibroblast growth factor receptor 1 (FGFR1)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathways, as evidenced by the inhibitory effects of pathway-specific inhibitors. We indeed confirmed that hBD-3 enhanced the phosphorylation of FGFR1, JAK2 and STAT3. Collectively, the current study provides novel evidence that hBD-3 might be a potential candidate for the treatment of wounds through its ability to promote wound healing, angiogenesis and fibroblast activation.


2002 ◽  
Vol 4 (1) ◽  
pp. 5-15 ◽  
Author(s):  
Beverly B. Childress ◽  
Joyce K. Stechmiller

Chronic wounds mainly affect elderly individuals and persons with comorbid diseases due to a compromised immune status. An age-related decline in immune function deters proper healing of wounds in an orderly and timely manner. Thus, older adults with 1 or more concomitant illnesses are more likely to experience and suffer from a nonhealing wound, which may drastically decrease their quality of life and financial resources. Novel therapies in wound care management rely heavily on our current knowledge of wound healing physiology. It is well established that normal wound healing occurs sequentially and is strictly regulated by pro-inflammatory cytokines and growth factors. A multitude of commercial products such as growth factors are available; however, their effectiveness in healing chronic wounds has yet to be proven. Recently, investigators have implicated nitric oxide (NO) in the exertion of regulatory forces on various cellular activities of the inflammatory and proliferative phases of wound healing. Gene therapy in animal studies has shown promising results and is furthering our understanding of impaired wound healing. The purpose of this article is to review the literature on NO and its role in wound healing. A discussion of the physiology of normal healing and the pathophysiology of chronic wounds is provided.


2018 ◽  
Vol 30 (02) ◽  
pp. 1850015
Author(s):  
Bahare Zihayat ◽  
Arash Khodadadi ◽  
Molook Torabi ◽  
Mohammad Mehdipour ◽  
Mohsen Basiri ◽  
...  

Diabetic ulcers (DUs) are a chronic, non-healing diabetes complication that leads to high hospital expenses and, in extreme cases, to amputation. Peripheral vascular diseases, diabetic neuropathy, abnormal cellular and cytokine activity are among the major factors that hinder diabetic wound healing. DUs represent an important challenge in the development of new and efficient wound dressings. The extracellular matrix (ECM) has been effectively used as a scaffold for constructive remodeling of multiple tissues in animal and human. Sheep’s urinary bladder matrix was evaluated for its wound healing activity in streptozotocin-induced diabetic rats using excision model. In this experiment, 48 male Sprague dawley rats weighing 220–250[Formula: see text]g were divided into four equal groups of control, vaseline, diabetics + (10[Formula: see text]mg/wound) and [Formula: see text] (50[Formula: see text]mg/wound). Diabetes was induced by intraperitoneal injection of streptozotocin (45[Formula: see text]mg/kg B.W) solved in 0.05[Formula: see text]M citrate buffer. Seven days after confirming diabetes statue, skin wounds were created on the back of each rat. Rate of wound healing and histological assay using hematoxylin and Eosin staining (H&E) were used for evaluation of the wound healing in different groups. ECM treated animals exhibited significant improvement in both wound area and rate of wound healing when compared to controls ([Formula: see text]). The ECM treated wounds were found to epithelize faster as compared to controls. The sheep’s ECM promotes significant wound healing in male diabetic rats and further studies on this activity in animal models and humans are suggested.


2021 ◽  
Vol 17 (2) ◽  
pp. 12-19
Author(s):  
O.I. Myronenko ◽  
T.I. Panova ◽  
L.V. Natrus ◽  
S.V. Verevka

Relevance. Diabetic foot syndrome is a common complication that is characterized by the development of chronic ulcers. Among the mechanisms of impaired wound healing, the leading role is played by disturbance of extracellular matrix homeostasis: chronic hyperglycemia, on the one hand, promotes the formation of so-called advanced glycation end products (AGEs), which mediate pro-inflammatory activation of immune cells, and on the other hand, inhibits fibroblasts proliferation and collagen production, disrupts the migration of keratinocytes and endothelial cells. Therefore, the elimination of AGEs is a pathogenetic approach in diabetic wound treatment. For this purpose, a composite consisting of polyspecific microbial proteinases fixed on polymeric porous nanoparticles was developed. The activity of matrix metalloproteinase-2 (MMP-2) was chosen as a prognostic indicator of chronic wound healing. Objective: to study the activity of MMP-2 in the tissues of the burn wound of rats with simulated diabetes mellitus under the influence of enzyme-containing nanoparticles. Materials and methods. N = 48 Wistar rats were used in the experiment. Diabetes mellitus was induced by administration of 50 mg/kg of streptozotocin. To model the wound in rats, a standard animal model of thermal burns by Walker and Mason was used. Thermal damage corresponded to the II-IIIA degree of burns, and occupied 19±1.6% of the total area of ​​animal skin. Rats were divided into two groups of 24 animals each: the DM group did not receive any treatment, and rats from the DM+T group were daily applied to the burn wound with the mentioned composite (enzyme-containing nanoparticles). Animals were removed from the experiment on days 3, 7, 14 and 21 of observation. The activity of MMP-2 in the tissues of the burn wound of diabetic rats was studied by gelatin zymography, expressed in arbitrary units (AU). Statistical data processing was performed in the software package SPSS Statistics Base, v.22 with Student and Scheffe tests. Results. The level of activity of MMP-2 in the tissues of the burn wound of rats in the DM group on the 3rd day of the study was 4.9 ± 1.3 AU, increased by 7 days (p <0.01) and reached a maximum level of 52.55 ± 3.06 AU at day 14 (p <0.01). On day 21, the activity of the test enzyme decreased by 8.5 AU (p <0.01), compared to day 14. On day 3 of the study in the DM+T group, the activity of MMP-2 in the diabetic wound was 15.93 ± 2.68 AU and gradually decreased (p <0.01) to 5.67 ± 2.67 AU on day 14. However, on day 21, the second peak (p <0.01) of the activity of the studied enzyme was observed - 33.64 ± 4.1 AU. When comparing the two groups (DmM and DM+T) on day 3 of the study, the activity of MMP-2 in the tissues of the burn wound of rats in the DM+T group was three times higher (p <0.01) than in the DM group. But from the 7th day the activity of MMP-2 in the DM group was higher than the DM+T group. On day 21 of the study, the level of MMP-2 in the DM group remained higher (p <0.01) than in the DM+T group. Conclusions. The use of enzyme-containing nanoparticles provides effective degradation of glycosylated components of the extracellular matrix (AGEs), thereby reducing the inflammatory process and activity of MMP-2, and promoting wound healing in rats with streptozotocin-induced diabetes.


2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Martina Balli ◽  
Jonathan Sai-Hong Chui ◽  
Paraskevi Athanasouli ◽  
Willy Antoni Abreu de Oliveira ◽  
Youssef El Laithy ◽  
...  

Impaired wound healing and tissue regeneration have severe consequences on the patient’s quality of life. Micrograft therapies are emerging as promising and affordable alternatives to improve skin regeneration by enhancing the endogenous wound repair processes. However, the molecular mechanisms underpinning the beneficial effects of the micrograft treatments remain largely unknown. In this study, we identified the active protein-1 (AP-1) member Fos-related antigen-1 (Fra-1) to play a central role in the extracellular signal-regulated kinase- (ERK-) mediated enhanced cell migratory capacity of soluble micrograft-treated mouse adult fibroblasts and in the human keratinocyte cell model. Accordingly, we show that increased micrograft-dependent in vitro cell migration and matrix metalloprotease activity is abolished upon inhibition of AP-1. Furthermore, soluble micrograft treatment leads to increased expression and posttranslational phosphorylation of Fra-1 and c-Jun, resulting in the upregulation of wound healing-associated genes mainly involved in the regulation of cell migration. Collectively, our work provides insights into the molecular mechanisms behind the cell-free micrograft treatment, which might contribute to future advances in wound repair therapies.


2019 ◽  
Vol 13 (1) ◽  
pp. 34-40
Author(s):  
Sukmawati Tansil Tan ◽  
Ricky Dosan

Wound healing consists of multiple structured mechanism and is influenced by various factors. Epithelialization is one of the major aspect in wound healing and inhibition of this mechanism will greatly impair wound healing. Epithelialization is a process where epithelial cells migrate upwards and repair the wounded area. This process is the most essential part in wound healing and occurs in proliferative phase of wound healing. Skin stem cells which reside in several locations of epidermis contribute in the re-epithelialization when the skin is damaged. Epithelialization process is activated by inflammatory signal and then keratinocyte migrate, differentiate and stratify to close the defect in the skin. Several theories of epithelialization model in wound healing have been proposed for decades and have shown the mechanism of epidermal cell migration during epithelialization even though the exact mechanism is still controversial. This process is known to be influenced by the wound environment where moist wound environment is preferred rather than dry wound environment. In dry wound environment, epithelialization is known to be inhibited because of scab or crust which is formed from dehydrated and dead cells. Moist wound environment enhances the epithelialization process by easier migration of epidermal cells, faster epithelialization, and prolonged presence of proteinases and growth factors. This article focuses on the epithelialization process in wound healing, epithelialization models, effects of wound environment on epithelialization and epithelialization as the basis for products that enhance wound healing.


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