scholarly journals The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice

2018 ◽  
Vol 19 (11) ◽  
pp. 3289 ◽  
Author(s):  
James Lee ◽  
Avril Robertson ◽  
Matthew Cooper ◽  
Kiarash Khosrotehrani
Keyword(s):  
Wound Healing ◽  
Small Molecule ◽  
Nlrp3 Inflammasome ◽  
Chronic Wounds ◽  
Inflammatory Diseases ◽  
Healing Process ◽  
Obese Mice ◽  
Impaired Wound Healing ◽  
Macrophage Polarisation ◽  
Inflammatory Conditions

The incidence of chronic wounds is escalating, and the associated healing process is especially problematic in an aging population with increased morbidity. Targeting increased inflammation in chronic wounds is a promising but challenging therapeutic strategy. Indeed, inflammation and especially macrophages are required for wound healing. As the NLRP3 inflammasome has been implicated with various other inflammatory diseases, in this study, we used MCC950—a selective NLRP3 small molecule inhibitor—on murine models of both acute and chronic wounds. This molecule, while tested for other inflammatory conditions, has never been investigated to reduce topical inflammation driving chronic wounds. We found that there were no significant differences when the treatment was applied either topically or orally in wild-type C57Bl/6 mice and that it even impaired wound healing in obese mice. The treatment was also unable to improve re-epithelialisation or angiogenesis, which are both required for the closure of wounds. We are inclined to believe that MCC950 may inhibit the closure of chronic wounds and that it does not alter wound-associated macrophage polarisation.

scholarly journals The potential of human induced pluripotent stem cells for modelling diabetic wound healing in vitro

2018 ◽  
Vol 132 (15) ◽  
pp. 1629-1643 ◽  
Author(s):  
Patricia E. Martin ◽  
Erin M. O’Shaughnessy ◽  
Catherine S. Wright ◽  
Annette Graham
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Chronic Wounds ◽  
Healing Process ◽  
Diabetic Patients ◽  
Impaired Wound Healing ◽  
Induced Pluripotent

Impaired wound healing and ulceration caused by diabetes mellitus, is a significant healthcare burden, markedly impairs quality of life for patients, and is the major cause of amputation worldwide. Current experimental approaches used to investigate the complex wound healing process often involve cultures of fibroblasts and/or keratinocytes in vitro, which can be limited in terms of complexity and capacity, or utilisation of rodent models in which the mechanisms of wound repair differ substantively from that in humans. However, advances in tissue engineering, and the discovery of strategies to reprogramme adult somatic cells to pluripotency, has led to the possibility of developing models of human skin on a large scale. Generation of induced pluripotent stem cells (iPSCs) from tissues donated by diabetic patients allows the (epi)genetic background of this disease to be studied, and the ability to differentiate iPSCs to multiple cell types found within skin may facilitate the development of more complex skin models; these advances offer key opportunities for improving modelling of wound healing in diabetes, and the development of effective therapeutics for treatment of chronic wounds.

Quercetin and its Natural Sources in Wound Healing Management

2019 ◽  
Vol 26 (31) ◽  
pp. 5825-5848 ◽  
Author(s):  
Nicoletta Polera ◽  
Mariateresa Badolato ◽  
Filomena Perri ◽  
Gabriele Carullo ◽  
Francesca Aiello
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Wound Care ◽  
Biological Activities ◽  
Healing Process ◽  
Wound Management ◽  
Wound Healing Process ◽  
Impaired Wound Healing ◽  
Care Research

Giving a glance to the report of Wound Care Market by Product updated in 2017, we can see that wound care market is expected to reach USD 22.01 billion by 2022 from USD 18.35 billion at a CAGR of 3.7%. Numerous factors are driving the growth of this market, including the increasing prevalence of chronic wounds and acute wounds, increasing aged population, rising R&D activities and advancement in the field of wound care research. Advanced wound management products are accounted for the largest market share in 2017. These evidences mean that the wound care research represents a Clinical Emergency other than an interesting Marketing tool. Drug therapies so far fight efficaciously with the opportunistic pathologies derived from chronic wounds, although an unsolved challenge is still finding a useful remedy to correct the impaired wound healing process and overcome the chronic wound state, to avoid bacterial rising and severe pain. Traditional medicinal plants have been widely used in the management of wounds and different plant extracts have been evaluated for their wound healing properties through both in vitro and in vivo studies. Their phytochemical components in particular quercetin, contribute to their remedial properties in wound repair. Quercetin has important biological activities related to the improvement of the wound healing process. The present review discusses and focuses on the latest findings of the wound healing properties of quercetin, alone or as a part of plant extract, and its role as a new frontier in wound repair.

NLRP3 activation induced by neutrophil extracellular traps sustains inflammatory response in the diabetic wound

2019 ◽  
Vol 133 (4) ◽  
pp. 565-582 ◽  
Author(s):  
Dan Liu ◽  
Peilang Yang ◽  
Min Gao ◽  
Tianyi Yu ◽  
Yan Shi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Healing Process ◽  
Receptor Protein ◽  
Main Role ◽  
Diabetic Wound ◽  
Impaired Wound Healing ◽  
Extracellular Traps ◽  
Diabetic Wounds

Abstract Persistent inflammatory response in the diabetic wound impairs the healing process, resulting in significant morbidity and mortality. Mounting evidence indicate that the activation of Nod-like receptor protein (NLRP) 3 inflammasome in macrophages (MΦ) contributes to the sustained inflammatory response and impaired wound healing associated with diabetes. However, the main trigger of NLRP3 inflammasome in the wounds is not known. Neutrophils, as sentinels of the innate immune system and key stimulators of MΦ, are immune cells that play the main role in the early phase of healing. Neutrophils release extracellular traps (NETs) as defense against pathogens. On the other hand, NETs induce tissue damage. NETs have been detected in the diabetic wound and implicated in the impaired healing process, but the mechanism of NETs suspend wound healing and its role in fostering inflammatory dysregulation are elusive. Here, we report that NLRP3 and NETs production are elevated in human and rat diabetic wounds. NETs overproduced in the diabetic wounds triggered NLRP3 inflammasome activation and IL-1β release in MΦ. Furthermore, NETs up-regulated NLRP3 and pro-IL-1β levels via the TLR-4/TLR-9/NF-κB signaling pathway. They also elicited the generation of reactive oxygen species, which facilitated the association between NLRP3 and thioredoxin-interacting protein, and activated the NLRP3 inflammasome. In addition, NET digestion by DNase I alleviated the activation of NLRP3 inflammasome, regulated the immune cell infiltration, and accelerated wound healing in diabetic rat model. These findings illustrate a new mechanism by which NETs contribute to the activation of NLRP3 inflammasome and sustained inflammatory response in the diabetic wound.

Wound Healing in the Golden Agers: What We Know and the Possible Way Ahead

2021 ◽  
pp. 153473462110378
Author(s):  
Aakansha Giri Goswami ◽  
Somprakas Basu ◽  
Vijay Kumar Shukla
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Wound Care ◽  
Financial Burden ◽  
Healing Process ◽  
The Elderly ◽  
Wound Healing Process ◽  
Impaired Wound Healing ◽  
Age Related

While “population aging” is an accomplishment that deserves acclamation, it is in itself a tremendous challenge. Age-related skin changes, impaired wound healing, and concurrent comorbidities are the deadly triad that contribute most to the development of nonhealing chronic wounds in the elderly. This imposes enormous medical, social, and financial burden. With the rising trend in the aging population, this problem is likely to exacerbate unless multidisciplinary, rapt wound care strategies are developed. The last decade was dedicated to understand the basic biology underlying the wound healing process but most in vitro and animal model studies translated poorly to human conditions. Forthcoming, the focus is on the development of diagnostic and therapeutic strategies to improve healing in this vulnerable age group. Further, understanding the complex pathobiology of cellular senescence and wound healing process is required to develop focused therapy for these “problem wounds” in the elderly.

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 Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2554
Author(s):  
Marek Konop ◽  
Anna K. Laskowska ◽  
Mateusz Rybka ◽  
Ewa Kłodzińska ◽  
Dorota Sulejczak ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Healing Process ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Diabetic Mice ◽  
Full Thickness ◽  
Skin Wound Healing ◽  
Impaired Wound Healing

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

scholarly journals Migration and Proliferation Effects of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) and Thymoquinone (TQ) on In Vitro Wound Healing Models

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Henna Roshini Alexander ◽  
Sharifah Sakinah Syed Alwi ◽  
Latifah Saiful Yazan ◽  
Fatin Hanani Zakarial Ansar ◽  
Yong Sze Ong
Keyword(s):  
Wound Healing ◽  
Nigella Sativa ◽  
Drug Carrier ◽  
Healing Process ◽  
Diabetic Patients ◽  
Nanostructured Lipid Carrier ◽  
Impaired Wound Healing ◽  
And Migration ◽  
Proliferation And Migration

Wound healing is a regulated biological event that involves several processes including infiltrating leukocyte subtypes and resident cells. Impaired wound healing is one of the major problems in diabetic patients due to the abnormal physiological changes of tissues and cells in major processes. Thymoquinone, a bioactive compound found in Nigella sativa has been demonstrated to possess antidiabetic, anti-inflammatory, and antioxidant effects. Today, the rapidly progressing nanotechnology sets a new alternative carrier to enhance and favour the speed of healing process. In order to overcome its low bioavailability, TQ is loaded into a colloidal drug carrier known as a nanostructured lipid carrier (NLC). This study aimed to determine the effect of TQ-NLC and TQ on cell proliferation and migration, mode of cell death, and the antioxidant levels in normal and diabetic cell models, 3T3 and 3T3-L1. Cytotoxicity of TQ-NLC and TQ was determined by MTT assay. The IC10 values obtained for 3T3-L1 treated with TQ-NLC and TQ for 24 hours were 4.7 ± 3.3 and 5.3 ± 0.6 μM, respectively. As for 3T3, the IC10 values obtained for TQ-NLC and TQ at 24 hours were 4.3 ± 0.17 and 3.9 ± 2.05 μM, respectively. TQ-NLC was observed to increase the number of 3T3 and 3T3-L1 healthy cells (87–95%) and gradually decrease early apoptotic cells in time- and dose-dependant manner compared with TQ. In the proliferation and migration assay, 3T3-L1 treated with TQ-NLC showed higher proliferation and migration rate (p<0.05) compared with TQ. TQ-NLC also acted as an antioxidant by reducing the ROS levels in both cells after injury at concentration as low as 3 μM. Thus, this study demonstrated that TQ-NLC has better proliferation and migration as well as antioxidant effect compared with TQ especially on 3T3-L1 which confirms its ability as a good antidiabetic and antioxidant agent.

scholarly journals Polymer-Based Scaffolds Loaded with Aloe vera Extract for the Treatment of Wounds

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 961
Author(s):  
Sibusiso Alven ◽  
Vuyolwethu Khwaza ◽  
Opeoluwa O. Oyedeji ◽  
Blessing A. Aderibigbe
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Mechanical Performance ◽  
Healing Process ◽  
Aloe Vera ◽  
Antimicrobial Properties ◽  
Biological Properties ◽  
Wound Management ◽  
Wound Healing Process ◽  
Treatment Of Wounds

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial properties, poor biodegradability and biocompatibility, and weak mechanical performance. Plant extracts, such as Aloe vera, have attracted significant attention in wound management because of their interesting biological properties. Aloe vera is composed of essential constituents beneficial for the wound healing process, such as amino acids, vitamins C and E, and zinc. Aloe vera influences numerous factors that are involved in wound healing and stimulates accelerated healing. This review reports the therapeutic outcomes of aloe vera extract-loaded polymer-based scaffolds in wound management.

Identifying New Pathways and Targets for Wound Healing and Therapeutics from Natural Sources

2021 ◽  
Vol 18 ◽  
Author(s):  
Xinchi Feng ◽  
Jinsong Hao
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wounds ◽  
Wound Care ◽  
Healing Process ◽  
Unmet Need ◽  
Wound Dressings ◽  
Wound Healing Process ◽  
Natural Sources ◽  
Viable Approach

: Chronic wounds remain a significant public problem and the development of wound treatments has been a research focus for the past few decades. Despite advances in the products derived from endogenous substances involved in a wound healing process (e.g. growth factors, stem cells, and extracellular matrix), effective and safe wound therapeutics are still limited. There is an unmet need to develop new therapeutics. Various new pathways and targets have been identified and could become a molecular target in designing novel wound agents. Importantly, many existing drugs that target these newly identified pathways could be repositioned for wound therapy, which will facilitate fast translation of research findings to clinical applications. This review discusses the newly identified pathways/targets and their potential uses in the development of wound therapeutics. Some herbs and amphibian skins have been traditionally used for wound repairs and their active ingredients have been found to act in these new pathways. Hence, screening these natural products for novel wound therapeutics remains a viable approach. The outcomes of wound care using natural wound therapeutics could be improved if we can better understand their cellular and molecular mechanisms and fabricate them in appropriate formulations, such as using novel wound dressings and nano-engineered materials. Therefore, we also provide an update on the advances in the wound therapeutics from natural sources. Overall, this review offers new insights into novel wound therapeutics.

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