scholarly journals Parameter-Dependency of Low-Intensity Vibration for Wound Healing in Diabetic Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Rita E. Roberts ◽  
Onur Bilgen ◽  
Rhonda D. Kineman ◽  
Timothy J. Koh
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Closure ◽  
Chronic Wounds ◽  
Low Frequency ◽  
Whole Body ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Low Intensity ◽  
Low Intensity Vibration

Chronic wounds in diabetic patients represent an escalating health problem, leading to significant morbidity and mortality. Our group previously reported that whole body low-intensity vibration (LIV) can improve angiogenesis and wound healing in diabetic mice. The purpose of the current study was to determine whether effects of LIV on wound healing are frequency and/or amplitude dependent. Wound healing was assessed in diabetic (db/db) mice exposed to one of four LIV protocols with different combinations of two acceleration magnitudes (0.3 and 0.6 g) and two frequencies (45 and 90 Hz) or in non-vibration sham controls. The low acceleration, low frequency protocol (0.3 g and 45 Hz) was the only one that improved wound healing, increasing angiogenesis and granulation tissue formation, leading to accelerated re-epithelialization and wound closure. Other protocols had little to no impact on healing with some evidence that 0.6 g accelerations negatively affected wound closure. The 0.3 g, 45 Hz protocol also increased levels of insulin-like growth factor-1 and tended to increase levels of vascular endothelial growth factor in wounds, but had no effect on levels of basic fibroblast growth factor or platelet derived growth factor-bb, indicating that this LIV protocol induces specific growth factors during wound healing. Our findings demonstrate parameter-dependent effects of LIV for improving wound healing that can be exploited for future mechanistic and therapeutic studies.

scholarly journals Lupeol, a Dietary Triterpene, Enhances Wound Healing in Streptozotocin-Induced Hyperglycemic Rats with Modulatory Effects on Inflammation, Oxidative Stress, and Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Fernando Pereira Beserra ◽  
Ana Júlia Vieira ◽  
Lucas Fernando Sérgio Gushiken ◽  
Eduardo Oliveira de Souza ◽  
Maria Fernanda Hussni ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Inflammatory Cell ◽  
Chronic Wounds ◽  
Treated Group ◽  
Diabetic Patients ◽  
Impaired Wound Healing ◽  
Collagen Iii ◽  
Wound Healing Activity ◽  
Immunohistochemical Analyses

Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. Natural products have shown to be effective in treating skin wounds. Lupeol is known to stimulate angiogenesis, fibroblast proliferation, and expressions of cytokines and growth factors involved in wound healing. The study is performed to evaluate the wound healing activity of lupeol in streptozotocin-induced hyperglycemic rats by macroscopical, histological, immunohistochemical, immunoenzymatic, and molecular methods. Percentage of wound closure and contraction was increased in the lupeol-treated group when compared to the Lanette group. Histopathological observation revealed decreased inflammatory cell infiltration and increased proliferation of fibroblasts, vascularization, and deposition of collagen fibers after lupeol treatment. Immunohistochemical analyses showed decreased intensity of NF-κB and increased intensity of FGF-2, TGF-β1, and collagen III. ELISA results revealed downregulated IL-6 levels and upregulated IL-10 levels in response to lupeol. The mRNA expression levels of Hif-1α, Sod-2, and Ho-1 were significantly increased in response to lupeol as compared to Lanette whereas Nf-κb and Vegf-A levels were decreased in relation to insulin and lupeol treatment. These findings indicate that lupeol possesses wound healing potential in hyperglycemic conditions and may be useful as a treatment for chronic wounds in diabetic patients.

scholarly journals Low-Intensity Vibration Improves Angiogenesis and Wound Healing in Diabetic Mice

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e91355 ◽  
Author(s):  
Eileen M. Weinheimer-Haus ◽  
Stefan Judex ◽  
William J. Ennis ◽  
Timothy J. Koh
Keyword(s):  
Wound Healing ◽  
Diabetic Mice ◽  
Low Intensity ◽  
Low Intensity Vibration

scholarly journals Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix

2021 ◽  
Vol 12 ◽  
pp. 204173142199975
Author(s):  
Jihyun Kim ◽  
Kyoung-Mi Lee ◽  
Seung Hwan Han ◽  
Eun Ae Ko ◽  
Dong Suk Yoon ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Type I ◽  
Diabetic Mice ◽  
Patients With Diabetes ◽  
Diabetic Wound Healing ◽  
Epidermal Growth ◽  
Wound Healing Effect ◽  
Growth Factor Production

Patients with diabetes experience impaired growth factor production such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), and they are reportedly involved in wound healing processes. Here, we report dual growth factor-loaded hyaluronate collagen dressing (Dual-HCD) matrix, using different ratios of the concentration of stabilized growth factors—stabilized-EGF (S-EGF) and stabilized-bFGF (S-bFGF). At first, the optimal concentration ratio of S-EGF to S-bFGF in the Dual-HCD matrix is determined to be 1:2 in type I diabetic mice. This Dual-HCD matrix does not cause cytotoxicity and can be used in vivo. The wound-healing effect of this matrix is confirmed in type II diabetic mice. Dual HCD enhances angiogenesis which promotes wound healing and thus, it shows a significantly greater synergistic effect than the HCD matrix loaded with a single growth factor. Overall, we conclude that the Dual-HCD matrix represents an effective therapeutic agent for impaired diabetic wound healing.

scholarly journals Sustained Release of Insulin-Like Growth Factor-1 from Bombyx mori L. Silk Fibroin Delivery for Diabetic Wound Therapy

2021 ◽  
Vol 22 (12) ◽  
pp. 6267
Author(s):  
Meng-Jin Lin ◽  
Mei-Chun Lu ◽  
Hwan-You Chang
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Sustained Release ◽  
Silk Fibroin ◽  
Granulation Tissue ◽  
Release Rate ◽  
Insulin Like Growth Factor ◽  
Diabetic Wound ◽  
Diabetic Mice ◽  
Wound Therapy

The goals of this study are to develop a high purity patented silk fibroin (SF) film and test its suitability to be used as a slow-release delivery for insulin-like growth factor-1 (IGF-1). The release rate of the SF film delivering IGF-1 followed zero-order kinetics as determined via the Ritger and Peppas equation. The release rate constant was identified as 0.11, 0.23, and 0.09% h−1 at 37 °C for SF films loaded with 0.65, 6.5, and 65 pmol IGF-1, respectively. More importantly, the IGF-1 activity was preserved for more than 30 days when complexed with the SF film. We show that the IGF-1-loaded SF films significantly accelerated wound healing in vitro (BALB/3T3) and in vivo (diabetic mice), compared with wounds treated with free IGF-1 and an IGF-1-loaded hydrocolloid dressing. This was evidenced by a six-fold increase in the granulation tissue area in the IGF-1-loaded SF film treatment group compared to that of the PBS control group. Western blotting analysis also demonstrated that IGF-1 receptor (IGF1R) phosphorylation in diabetic wounds increased more significantly in the IGF-1-loaded SF films group than in other experimental groups. Our results suggest that IGF-1 sustained release from SF films promotes wound healing through continuously activating the IGF1R pathway, leading to the enhancement of both wound re-epithelialization and granulation tissue formation in diabetic mice. Collectively, these data indicate that SF films have considerable potential to be used as a wound dressing material for long-term IGF-1 delivery for diabetic wound therapy.

scholarly journals Surgical Strategies to Promote Cutaneous Healing

2021 ◽  
Vol 9 (2) ◽  
pp. 45
Author(s):  
Ines Maria Niederstätter ◽  
Jennifer Lynn Schiefer ◽  
Paul Christian Fuchs
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Chronic Wounds ◽  
Treatment Algorithm ◽  
Surgical Site Infections ◽  
Repair Process ◽  
Suture Technique ◽  
The Body ◽  
Wound Debridement ◽  
Reconstructive Ladder

Usually, cutaneous wound healing does not get impeded and processes uneventfully, reaching wound closure easily. The goal of this repair process is to restore the integrity of the body surface by creating a resilient and stable scar. Surgical practice and strategies have an impact on the course of wound healing and the later appearance of the scar. By considering elementary surgical principles, such as the appropriate suture material, suture technique, and timing, optimal conditions for wound healing can be created. Wounds can be differentiated into clean wounds, clean–contaminated wounds, contaminated, and infected/dirty wounds, based on the degree of colonization or infection. Furthermore, a distinction is made between acute and chronic wounds. The latter are wounds that persist for longer than 4–6 weeks. Care should be taken to avoid surgical site infections in the management of wounds by maintaining sterile working conditions, using antimicrobial working techniques, and implementing the principles of preoperative antibiotics. Successful wound closure is influenced by wound debridement. Wound debridement removes necrotic tissue, senescent and non-migratory cells, bacteria, and foreign bodies that impede wound healing. Additionally, the reconstructive ladder is a viable and partially overlapping treatment algorithm in plastic surgery to achieve successful wound closure.

scholarly journals A small molecule HIF-1α stabilizer that accelerates diabetic wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guodong Li ◽  
Chung-Nga Ko ◽  
Dan Li ◽  
Chao Yang ◽  
Wanhe Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Small Molecule ◽  
Hypoxia Inducible Factor ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Von Hippel Lindau ◽  
Design And Synthesis

AbstractImpaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL–HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.

scholarly journals Role of Nerve Growth Factor in Cutaneous Wound Healing: Accelerating Effects in Normal and Healing-impaired Diabetic Mice

1998 ◽  
Vol 187 (3) ◽  
pp. 297-306 ◽  
Author(s):  
Hiroshi Matsuda ◽  
Hiromi Koyama ◽  
Hiroaki Sato ◽  
Junko Sawada ◽  
Atsuko Itakura ◽  
...  
Keyword(s):  
Wound Healing ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Granulation Tissue ◽  
Messenger Rna ◽  
Biological Activities ◽  
Serum Levels ◽  
Blood Stream ◽  
Diabetic Mice ◽  
Nerve Growth

Four full-thickness skin wounds made in normal mice led to the significant increase in levels of nerve growth factor (NGF) in sera and in wounded skin tissues. Since sialoadenectomy before the wounds inhibited the rise in serum levels of NGF, the NGF may be released from the salivary gland into the blood stream after the wounds. In contrast, the fact that messenger RNA and protein of NGF were detected in newly formed epithelial cells at the edge of the wound and fibroblasts consistent with the granulation tissue produced in the wound space, suggests that NGF was also produced at the wounded skin site. Topical application of NGF into the wounds accelerated the rate of wound healing in normal mice and in healing-impaired diabetic KK/Ta mice. This clinical effect of NGF was evaluated by histological examination; the increases in the degree of reepithelialization, the thickness of the granulation tissue, and the density of extracellular matrix were observed. NGF also increased the breaking strength of healing linear wounds in normal and diabetic mice. These findings suggested that NGF immediately and constitutively released in response to cutaneous injury may contribute to wound healing through broader biological activities, and NGF improved the diabetic impaired response of wound healing.

Effectiveness of a synthetic human recombinant epidermal growth factor in diabetic patients wound healing : Pilot , double‐blind , randomized clinical controlled trial

2021 ◽  
Author(s):  
Bianca Campos Oliveira ◽  
Beatriz Guitton Renaud Baptista Oliveira ◽  
Gabriela Deutsch ◽  
Fernanda Soares Pessanha ◽  
Selma Rodrigues Castilho
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Controlled Trial ◽  
Diabetic Patients ◽  
Double Blind ◽  
Epidermal Growth

scholarly journals Effects of Hyperbaric Oxygen on Inflammatory Response to Wound and Trauma: Possible Mechanism of Action

2006 ◽  
Vol 6 ◽  
pp. 425-441 ◽  
Author(s):  
Noori S. Al-Waili ◽  
Glenn J. Butler
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Inflammatory Response ◽  
Hyperbaric Oxygen ◽  
Mechanism Of Action ◽  
Chronic Wounds ◽  
Carbon Monoxide Poisoning ◽  
Clinical Applications ◽  
No Production ◽  
Mediators Of Inflammation

There is growing interest in expanding the clinical applications for HBO2(hyperbaric oxygen therapy) into new medical and surgical fields. The pathophysiology of response towards wounds, infection, trauma, or surgery involves various chemical mediators that include cytokines, prostaglandins (PGs), and nitric oxide (NO). The beneficial role played by HBO2in wound healing, carbon monoxide poisoning, decompression sickness, and other indications is well documented. However, the exact mechanism of action is still poorly understood. This review addresses the effects of HBO2on PGs, NO, and cytokines involved in wound pathophysiology and inflammation in particular. The results of this review indicate that HBO2has important effects on the biology of cytokines and other mediators of inflammation. HBO2causes cytokine down-regulation and growth factor up-regulation. HBO2transiently suppresses stimulus-induced proinflammatory cytokine production and affects the liberation of TNFα (tumor necrosis factor alpha) and endothelins. VEGF (vascular endothelial growth factor) levels are significantly increased with HBO2, whereas the value of PGE2 and COX-2 mRNA are markedly reduced. The effect of HBO2on NO production is not well established and more studies are required. In conclusion, cytokines, PGs, and NO may play a major role in the mechanism of action of HBO2 and further research could pave the way for new clinical applications for HBO2to be established. It could be proposed that chronic wounds persist due to an uncontrolled pathological inflammatory response in the wound bed and that HBO2enhances wound healing by damping pathological inflammation (anti-inflammatory effects); this hypothetical proposal remains to be substantiated with experimental results.

scholarly journals Adipose Stem Cells from Type 2 Diabetic Mice Exhibit Therapeutic Potential in Wound Healing

2020 ◽  
Author(s):  
Yongfa Sun ◽  
Lili Song ◽  
Yong Zhang ◽  
Hongjun Wang ◽  
Xiao Dong
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Skin Damage ◽  
Impaired Wound Healing ◽  
Collagen Iii

Abstract BACKGROUND: Diabetic patients suffer from impaired wound healing. Mesenchymal stem cell (MSC) therapy represents a promising approach toward improving skin wound healing through release of soluble growth factors and cytokines that stimulate new vessel formation and modulate inflammation. Whether adipose-derived MSCs (ASCs) from type 2 diabetes donors are suitable for skin damage repair remains largely unknown. METHODS: In this study, we compared the phenotype and functionality of ASCs harvested from high fat diet (HFD) and streptozotocin (STZ)-induced T2D or control mice, and assessed their abilities to promote wound healing in an excisional wound splinting mouse model with T2D. RESULTS: T2D ASCs expressed similar cellular markers as control ASCs, but secreted less hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β). T2D ASCs were somewhat less effective in promoting healing of the wound, as manifested by slightly reduced re-epithelialization, cutaneous appendage regeneration, and collagen III deposition in wound tissues. In vitro, T2D ASCs promoted proliferation and migration of skin fibroblasts to a comparable extent as control ASCs via suppression of inflammation and macrophage infiltration. CONCLUSIONS: From these findings, we conclude that, although ASCs from T2D mice are marginally inferior to control ASCs, they possess comparable therapeutic effects in wound healing.

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