scholarly journals pH-switchable nanozyme cascade catalysis: a strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in diabetic ulcer

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Xuancheng Du ◽  
Bingqing Jia ◽  
Weijie Wang ◽  
Chengmei Zhang ◽  
Xiangdong Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
Glucose Oxidase ◽  
Cascade Reaction ◽  
Temporal Modulation ◽  
Diabetic Ulcer ◽  
Normal Tissues ◽  
Normal Wound Healing ◽  
Inflammatory Phase ◽  
Cascade Catalysis

AbstractThe management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe3O4-GOx). The Fe3O4-GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial–temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases. Graphical Abstract

Angiogenic Nanoscaffold Accelerates Diabetic Wound Healing and Improves Wound Tissue Strength in db/db Mice

2009 ◽  
Author(s):  
Swathi Balaji ◽  
Abdul Q. Sheikh ◽  
Lee Morris ◽  
Foong Y. Lim ◽  
Timothy M. Crombleholme ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wound Healing Process ◽  
Diabetic Patients ◽  
Diabetic Wound ◽  
Normal Wound Healing ◽  
Inflammatory Phase ◽  
Diabetic Wound Healing ◽  
Ecm Degradation ◽  
Chronic Ulcers

Chronic ulcers are a leading cause of morbidity in diabetic patients. Diabetes is associated with major changes in the wound microenvironment and disruption of normal wound healing process, characterized by a prolonged inflammatory phase with elevated levels of wound proteases and increased degradation of extracellular matrix (ECM) components [1]. This impedes wound healing due to a lack of provisional matrix, impaired recruitment and survival of endothelial (EC) and endothelial precursor (EPC) cells, and insufficient neovascularization, resulting in delayed healing. Therefore, strategies focused on restoring the diabetic wound microenvironment by decreasing ECM degradation and promoting neovascularization are promising for development of new therapies to treat chronic diabetic ulcers.

scholarly journals Insights into Host–Pathogen Interactions in Biofilm-Infected Wounds Reveal Possibilities for New Treatment Strategies

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 396
Author(s):  
Hannah Trøstrup ◽  
Anne Sofie Boe Laulund ◽  
Claus Moser
Keyword(s):  
Wound Healing ◽  
Host Response ◽  
Chronic Wounds ◽  
Therapeutic Potential ◽  
Recent Observation ◽  
Treatment Strategies ◽  
Normal Wound Healing ◽  
Inflammatory Phase ◽  
The Impact

Normal wound healing occurs in three phases—the inflammatory, the proliferative, and the remodeling phase. Chronic wounds are, for unknown reasons, arrested in the inflammatory phase. Bacterial biofilms may cause chronicity by arresting healing in the inflammatory state by mechanisms not fully understood. Pseudomonas aeruginosa, a common wound pathogen with remarkable abilities in avoiding host defense and developing microbial resistance by biofilm formation, is detrimental to wound healing in clinical studies. The host response towards P. aeruginosa biofilm-infection in chronic wounds and impact on wound healing is discussed and compared to our own results in a chronic murine wound model. The impact of P. aeruginosa biofilms can be described by determining alterations in the inflammatory response, growth factor profile, and count of leukocytes in blood. P. aeruginosa biofilms are capable of reducing the host response to the infection, despite a continuously sustained inflammatory reaction and resulting local tissue damage. A recent observation of in vivo synergism between immunomodulatory and antimicrobial S100A8/A9 and ciprofloxacin suggests its possible future therapeutic potential.

Wound Healing In Glaucoma

2013 ◽  
Author(s):  
Kimberly A. Mankiewicz ◽  
Leonard K. Seibold
Keyword(s):  
Wound Healing ◽  
Blood Cells ◽  
Healing Process ◽  
White Blood Cells ◽  
Glaucoma Surgery ◽  
Scar Formation ◽  
Wound Site ◽  
Normal Wound Healing ◽  
Inflammatory Phase ◽  
Repair Phase

The goal of wound healing in most surgeries is to bring the injured tissue back to its original state to prevent the wound from reopening. However, in glaucoma surgery, the goal is to have incomplete wound healing. Scar formation prevents the filtering mechanism and bleb from functioning properly, leading to poor pressure control and failure of the surgery. However, if there is too little wound healing, surgical failure may be marked by overfiltration and hypotony. Several modulators are currently used in conjunction with glaucoma surgery, and new targets are under investigation to improve our ability to control the healing process. Normal wound healing occurs in 3 phases: the inflammatory phase, the proliferative/repair phase, and the remodeling phase. In the inflammatory phase, blood cells and plasma proteins are released around the wound site. These proteins attract other wound healing factors, such as cytokines and growth factors. White blood cells are also recruited to the site, clearing out undesired cellular debris through phagocytosis. Additionally, platelet aggregation and fibrin clot formation occur. In the proliferative/repair phase, fibroblasts, crucial cells for tissue repair and scarring, begin reforming the extracellular matrix (ECM) and other components of connective tissue. Angiogenesis also occurs, and the wound begins to close. In the final phase, blood vessels are resorbed and fibroblasts disperse. Fibroblasts produce matrix metalloproteinases that, along with collagen and elastin, allowing for wound remodeling and scar formation. The modulators used in glaucoma surgery, as well as new agents in development, disrupt various aspects of this cycle. Use of topical corticosteroids in conjunction with filtering surgery is a routine part of postoperative management and has been for many decades. Corticosteroids blunt the wound healing response by altering the inflammatory phase through reducing the amount of inflammatory cells and cytokines that migrate to the wound site. Corticosteroids also prevent the complexing and conversion of inflammatory mediators, as well as reduce vascular permeability to limit mobility of wound healing factors to the wound site.

scholarly journals WOUND HEALING PROPERTIES OF PURANA GHRITA WITH SPECIAL REFERENCE TO NON-HEALING DIABETIC ULCER- A case Study

2019 ◽  
Vol 7 (07) ◽  
Author(s):  
Kirti Mandar Deo
Keyword(s):  
Wound Healing ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Modern Medicine ◽  
Diabetic Ulcer ◽  
Inflammatory Phase ◽  
Ayurvedic Treatment

Diabetic foot ulcer (DFU) is one of the major complications found in 15% of diabetics. It significantly reduces the quality of life. In DFU there is a prolonged inflammatory phase, delayed mature granulation tissue formation and reduction in wound tensile strength. The recommended line of treatment as per modern medicine includes Blood sugar control, removal of dead tissue & Wound dressing.According to Charak Samhita, Prameha Pidaka are caused due to upeksha (neglect) of underlying Prameha. Prameha Pidaka are of darun type and have 7 subtypes. Purana Ghrita plays significant role in wound healing in non-healing diabetic ulcer.Objective: To study the effect of Purana Ghrita in non-healing diabetic ulcer.Methods: In the case presented here, a male patient aged 70 years with type 2 diabetes, was admitted in the hospital for 2 months for the treatment of Non- healing diabetic ulcer on the sole of left foot. Allopathy treatment did not give desired results. Hence after 2 months of admittance, Ayurvedic treatment was introduced for DFU. Dressing of wound was done by mixture of Purana Ghrita, honey, Triphala Churna and Haridra Churna along with the dressing, Rasapachak, Raktapachak, Mansapachak, Gudmaradi vati, Aarogyavardhini vati & Sanjivani guti were used internally at different times. Result and Conclusion: With above mentioned treatment the non-healing diabetic ulcer healed and the patient was discharged after 30 days.Purana Ghrita has Vrana nashak qualities. It cleanses as well as heals i.e. it has Shodhan and Ropan properties.

The Skin and the Physiology of Normal Wound Healing

2020 ◽  
Author(s):  
Timothy W. King ◽  
Sahil K. Kapur
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Wound Care ◽  
Normal Wound Healing ◽  
Inflammatory Phase ◽  
Complex Process

This review presents normal wound healing as a complex process that is generally carried out in three overlapping stages: an inflammatory phase, a proliferative phrase (made up of fibroplasia, contraction, neovascularization, and granulation), and a remodeling phase. In addition, wound healing occurs under the influence of multiple cytokines, growth factors, and extracellular matrix signals. Figures show the layers of the skin and the cycles of wound healing.  This review contains 6 highly rendered figures, 8 tables, and 47 references Keywords: wound, wound care, healing, epithelialization, migration, granulation

Abstract 144: Bone-Marrow Chimeras Demonstrate that the Epigenetic Signature in the Bone Marrow Myeloid Cells Influences the Peripheral Wound M1-Dominant Macrophage Phenotype

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Katherine A Gallagher ◽  
Amrita Joshi ◽  
Emily Hogikyan ◽  
Dawn Coleman ◽  
William Carson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Wound Healing ◽  
Normal Diet ◽  
Blood Analysis ◽  
Macrophage Phenotype ◽  
Chimeric Mice ◽  
Impaired Wound Healing ◽  
Normal Wound Healing ◽  
Dominant Phenotype ◽  
Inflammatory Phase

Introduction: Diabetic wounds are characterized by a chronic inflammatory state that is maintained by overexpression of pro-inflammatory cytokines generated by macrophages. In normal wound healing, macrophages mobilized from the circulation initially exhibit an M1 phenotype and secrete pro-inflammatory mediators (i.e., IL-12) followed by a prolonged M2 anti-inflammatory phase. In type 2 diabetes (T2D), this M1 to M2 switch appears to be markedly attenuated. We have previously demonstrated that post-translational histone methylation changes in BM cells are maintained in peripheral macrophages and promote an M1 dominant phenotype in T2D wounds that result in impaired wound healing. We hypothesize that chimeric mice reconstituted with bone marrow from our T2D murine model will demonstrate delayed wound healing and expression of this epigenetic signature in peripheral wound macrophages. Methods: BM chimeras were created using GFP+ mice on a C57BL/6 background. GFP+ mice were fed a high-fat diet (HFD, 60% fat) for 14 weeks and BM from these mice and normal diet (ND, 12% fat) mice was transferred into irradiated recipients. Change in wound area compared to initial wound size using Image J software (NIH) at day 3 post-wounding. Levels of the demethylase enzyme, Jmjd3, in macrophages (CD11b + ) MACS isolated from wounds at day 3 were quantified by RT-PCR in ND→ND and HFD→ND GFP + chimeric mice. (N=8) Data are expressed as mean ± S.E. Results: Peripheral blood analysis was performed weekly and at 8 weeks confirmed 96.5% donor chimerism. Wound healing was significantly delayed in HFD→ND GFP + chimeric mice compared to controls and analysis of wound tissue macropahges in mice at day 3 post-wounding demonstrated increased Jmjd3 and IL-12 production. Discussion: Epigenetic changes in BM cells appear to be maintained in peripheral wound macrophages and contribute to increased M1 macrophages and impaired wound healing in T2D wounds.

The Skin and the Physiology of Normal Wound Healing

2020 ◽  
Author(s):  
Timothy W. King ◽  
Sahil K. Kapur
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Growth Factors ◽  
Wound Care ◽  
Normal Wound Healing ◽  
Inflammatory Phase ◽  
Complex Process

This review presents normal wound healing as a complex process that is generally carried out in three overlapping stages: an inflammatory phase, a proliferative phrase (made up of fibroplasia, contraction, neovascularization, and granulation), and a remodeling phase. In addition, wound healing occurs under the influence of multiple cytokines, growth factors, and extracellular matrix signals. Figures show the layers of the skin and the cycles of wound healing.  This review contains 6 highly rendered figures, 8 tables, and 47 references Keywords: wound, wound care, healing, epithelialization, migration, granulation

PHENOTYPIC HETEROGENEITY OF CARDIAC MACROPHAGES DURING WOUND HEALING FOLLOWING MYOCARDIAL INFARCTION: PERSPECTIVES IN CLINICAL RESEARCH

2018 ◽  
Vol 33 (2) ◽  
pp. 70-76 ◽  
Author(s):  
A. E. Gombozhapova ◽  
Yu. V. Rogovskaya ◽  
M. S. Rebenkova ◽  
J. G. Kzhyshkowska ◽  
V. V. Ryabov
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Cardiac Remodeling ◽  
Phenotypic Heterogeneity ◽  
Macrophage Infiltration ◽  
Myocardial Regeneration ◽  
Control Group ◽  
M2 Macrophage ◽  
Inflammatory Phase ◽  
Regenerative Phase

Purpose. Myocardial regeneration is one of the most ambitious goals in prevention of adverse cardiac remodeling. Macrophages play a key role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). We have accumulated data on macrophage properties ex vivo and in cell culture. However, there is no clear information about phenotypic heterogeneity of cardiac macrophages in patients with MI. The purpose of the project was to assess cardiac macrophage infiltration during wound healing following myocardial infarction in clinical settings taking into consideration experimental knowledge.Material and Methods. The study included 41 patients with fatal MI type 1. In addition to routine analysis, macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163, CD206, and stabilin-1 were considered as M2 macrophage biomarkers. Nine patients who died from noncardiovascular causes comprised the control group.Results. The intensity of cardiac macrophage infiltration was higher during the regenerative phase than during the inflammatory phase. Results of immunohistochemical analysis demonstrated the presence of phenotypic heterogeneity of cardiac macrophages in patients with MI. We noticed that numbers of CD68+, CD163+, CD206+, and stabilin-1+ macrophages depended on MI phase.Conclusion. Our study supports prospects for implementation of macrophage phenotyping in clinic practice. Improved understanding of phenotypic heterogeneity might become the basis of a method to predict adverse cardiac remodeling and the first step in developing myocardial regeneration target therapy.

scholarly journals Bv8-Like Toxin from the Frog Venom of Amolops jingdongensis Promotes Wound Healing via the Interleukin-1 Signaling Pathway

Toxins ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 15 ◽  
Author(s):  
Jiajia Chang ◽  
Xiaoqin He ◽  
Jingmei Hu ◽  
Peter Muiruri Kamau ◽  
Ren Lai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Signaling Pathway ◽  
Wide Spectrum ◽  
Interleukin 1 ◽  
Full Thickness ◽  
Mice Model ◽  
Small Peptides ◽  
Newborn Mice ◽  
Proliferative Effect ◽  
Inflammatory Phase

Prokineticins are highly conserved small peptides family expressed in all vertebrates, which contain a wide spectrum of functions. In this study, a prokineticin homolog (Bv8-AJ) isolated from the venom of frog Amolops jingdongensis was fully characterized. Bv8-AJ accelerated full-thickness wounds healing of mice model by promoting the initiation and the termination of inflammatory phase. Moreover, Bv8-AJ exerted strong proliferative effect on fibroblasts and keratinocytes isolated from newborn mice by activating interleukin (IL)-1 production. Our findings indicate that Bv8 is a potent wound healing regulator and may reveal the mechanism of rapid wound-healing in amphibian skins.

scholarly journals Inflammatory M1-like macrophages polarized by NK-4 undergo enhanced phenotypic switching to an anti-inflammatory M2-like phenotype upon co-culture with apoptotic cells

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Keizo Kohno ◽  
Satomi Koya-Miyata ◽  
Akira Harashima ◽  
Takahiko Tsukuda ◽  
Masataka Katakami ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Phenotypic Switching ◽  
Apoptotic Cells ◽  
Phenotypic Switch ◽  
Inflammatory Phase ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background NK-4 has been used to promote wound healing since the early-1950s; however, the mechanism of action of NK-4 is unknown. In this study, we examined whether NK-4 exerts a regulatory effect on macrophages, which play multiple roles during wound healing from the initial inflammatory phase until the tissue regeneration phase. Results NK-4 treatment of THP-1 macrophages induced morphological features characteristic of classically-activated M1 macrophages, an inflammatory cytokine profile, and increased expression of the M1 macrophage-associated molecules CD38 and CD86. Interestingly, NK-4 augmented TNF-α production by THP-1 macrophages in combination with LPS, Pam3CSK4, or poly(I:C). Furthermore, NK-4 treatment enhanced THP-1 macrophage phagocytosis of latex beads. These results indicate that NK-4 drives macrophage polarization toward an inflammatory M1-like phenotype with increased phagocytic activity. Efferocytosis is a crucial event for resolution of the inflammatory phase in wound healing. NK-4-treated THP-1 macrophages co-cultured with apoptotic Jurkat E6.1 (Apo-J) cells switched from an M1-like phenotype to an M2-like phenotype, as seen in the inverted ratio of TNF-α to IL-10 produced in response to LPS. We identified two separate mechanisms that are involved in this phenotypic switch. First, recognition of phosphatidylserine molecules on Apo-J cells by THP-1 macrophages downregulates TNF-α production. Second, phagocytosis of Apo-J cells by THP-1 macrophages and activation of PI3K/Akt signaling pathway upregulates IL-10 production. Conclusion It is postulated that the phenotypic switch from a proinflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype is dysregulated due to impaired efferocytosis of apoptotic neutrophils at the wound site. Our results demonstrate that NK-4 improves phagocytosis of apoptotic cells, suggesting its potential as a therapeutic strategy to resolve sustained inflammation in chronic wounds.

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