In vitro and in vivo wound healing-promoting activities of β-lapachone

2008 ◽  
Vol 295 (4) ◽  
pp. C931-C943 ◽  
Author(s):  
Hsiu-Ni Kung ◽  
Mei-Jun Yang ◽  
Chi-Fen Chang ◽  
Yat-Pang Chau ◽  
Kuo-Shyan Lu
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Healing Process ◽  
Cell Types ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Diabetic Patients ◽  
Impaired Wound Healing

Impaired wound healing is a serious problem for diabetic patients. Wound healing is a complex process that requires the cooperation of many cell types, including keratinocytes, fibroblasts, endothelial cells, and macrophages. β-Lapachone, a natural compound extracted from the bark of the lapacho tree ( Tabebuia avellanedae), is well known for its antitumor, antiinflammatory, and antineoplastic effects at different concentrations and conditions, but its effects on wound healing have not been studied. The purpose of the present study was to investigate the effects of β-lapachone on wound healing and its underlying mechanism. In the present study, we demonstrated that a low dose of β-lapachone enhanced the proliferation in several cells, facilitated the migration of mouse 3T3 fibroblasts and human endothelial EAhy926 cells through different MAPK signaling pathways, and accelerated scrape-wound healing in vitro. Application of ointment with or without β-lapachone to a punched wound in normal and diabetic ( db/ db) mice showed that the healing process was faster in β-lapachone-treated animals than in those treated with vehicle only. In addition, β-lapachone induced macrophages to release VEGF and EGF, which are beneficial for growth of many cells. Our results showed that β-lapachone can increase cell proliferation, including keratinocytes, fibroblasts, and endothelial cells, and migration of fibroblasts and endothelial cells and thus accelerate wound healing. Therefore, we suggest that β-lapachone may have potential for therapeutic use for wound healing.

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 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 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.

scholarly journals Puerarin Improves Dexamethasone-Impaired Wound Healing In Vitro and In Vivo by Enhancing Keratinocyte Proliferation and Migration

2021 ◽  
Vol 11 (19) ◽  
pp. 9343
Author(s):  
Ly Thi Huong Nguyen ◽  
Sang-Hyun Ahn ◽  
Min-Jin Choi ◽  
In-Jun Yang ◽  
Heung-Mook Shin
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wound Healing Process ◽  
Hacat Cells ◽  
Impaired Wound Healing ◽  
Keratinocyte Proliferation ◽  
And Migration ◽  
Proliferation And Migration

The delayed and impaired wound healing caused by dexamethasone (DEX) is commonly reported. Puerarin, the major isoflavone found in Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep promoted the wound healing process in diabetic rats. However, the effects and underlying mechanisms of puerarin on DEX-impaired wound healing have not been investigated. This study examined the potential uses of puerarin in upregulating keratinocyte proliferation and migration in dexamethasone (DEX)-suppressed wound healing model. The effects of puerarin on wound healing in vivo were investigated by taking full-thickness 5 mm punch biopsies from the dorsal skin of BALB/c mice and then treating them topically with 0.1% DEX. For the in vitro study, DEX-treated HaCaT cells were used to examine the effects of puerarin on DEX-induced keratinocyte proliferation and migration and the mechanisms of its action. Puerarin, when applied topically, accelerated the wound closure rate, increased the density of the capillaries, and upregulated the level of collagen fibers and TGF-β in the wound sites compared to the DEX-treated mice. Puerarin promoted the proliferation and migration of keratinocytes by activating the ERK and Akt signaling pathways in DEX-treated HaCaT cells. In conclusion, puerarin could be effective in reversing delayed and disrupted wound healing associated with DEX treatments.

Development of a novel keratin dressing which accelerates full-thickness skin wound healing in diabetic mice: In vitro and in vivo studies

2018 ◽  
Vol 33 (4) ◽  
pp. 527-540 ◽  
Author(s):  
Marek Konop ◽  
Joanna Czuwara ◽  
Ewa Kłodzińska ◽  
Anna K Laskowska ◽  
Urszula Zielenkiewicz ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Healing Process ◽  
Skin Wound ◽  
In Vivo Studies ◽  
Histopathological Analysis ◽  
Full Thickness ◽  
Impaired Wound Healing

Impaired wound healing is a major medical problem in diabetes. The objective of this study was to determine the possible application of an insoluble fraction of fur-derived keratin biomaterial as a wound dressing in a full thickness surgical skin wound model in mice ( n = 20) with iatrogenically induced diabetes. The obtained keratin dressing was examined in vitro and in vivo. In vitro study showed the keratin dressing is tissue biocompatible and non-toxic for murine fibroblasts. Antimicrobial examination revealed the keratin dressing inhibited the growth of S. aureus and E. coli. In vivo studies showed the obtained dressing significantly ( p < 0.05) accelerated healing during the first week after surgery compared to control wounds. Keratin dressings were incorporated naturally into granulation and regenerating tissue without any visible signs of inflammatory response, which was confirmed by clinical and histopathological analysis. It is one of the first studies to show application of insoluble keratin proteins and its properties as a wound dressing. The obtained keratin dressing accelerated wound healing in mice with iatrogenically induced diabetes. Therefore, it can be considered as a safe and efficient wound dressing. Although future studies are needed to explain the molecular mechanism behind fur-derived keratin effect during the multilayer wound healing process, our findings may open the way for a new class of insoluble fur keratin dressings in chronic difficult to heal wounds treatment.

scholarly journals Microcurrent Stimulation Triggers MAPK Signaling and TGF-β1 Release in Fibroblast and Osteoblast-Like Cell Lines

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1924
Author(s):  
Evangelia Konstantinou ◽  
Zoi Zagoriti ◽  
Anastasia Pyriochou ◽  
Konstantinos Poulas
Keyword(s):  
Wound Healing ◽  
Transforming Growth Factor Beta ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Mapk Signaling ◽  
Tgf Β1

Wound healing constitutes an essential process for all organisms and involves a sequence of three phases. The disruption or elongation of any of these phases can lead to a chronic or non-healing wound. Electrical stimulation accelerates wound healing by mimicking the current that is generated in the skin after any injury. Here, we sought to identify the molecular mechanisms involved in the healing process following in vitro microcurrent stimulation—a type of electrotherapy. Our results concluded that microcurrents promote cell proliferation and migration in an ERK 1/2- or p38-dependent way. Furthermore, microcurrents induce the secretion of transforming growth factor-beta-1 (TGF-β1) in fibroblasts and osteoblast-like cells. Interestingly, transcriptomic analysis uncovered that microcurrents enhance the transcriptional activation of genes implicated in Hedgehog, TGF-β1 and MAPK signaling pathways. Overall, our results demonstrate that microcurrents may enhance wound closure through a combination of signal transductions, via MAPK’s phosphorylation, and the transcriptional activation of specific genes involved in the healing process. These mechanisms should be further examined in vivo, in order to verify the beneficial effects of microcurrents in wound or fracture healing.

scholarly journals Argon Mitigates Impaired Wound Healing Process and Enhances Wound Healing In Vitro and In Vivo

Theranostics ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 477-490 ◽  
Author(s):  
Jiaolin Ning ◽  
Hailin Zhao ◽  
Bin Chen ◽  
Emma Zheling Mi ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wound Healing Process ◽  
Impaired Wound Healing

scholarly journals Polydeoxyribonucleotide: A Promising Biological Platform to Accelerate Impaired Skin Wound Healing

2021 ◽  
Vol 14 (11) ◽  
pp. 1103
Author(s):  
Mariarosaria Galeano ◽  
Giovanni Pallio ◽  
Natasha Irrera ◽  
Federica Mannino ◽  
Alessandra Bitto ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Receptor Activation ◽  
Healing Time ◽  
Wound Healing Process ◽  
Search Term ◽  
Skin Wound Healing ◽  
Impaired Wound Healing

The normal wound healing process is characterized by a complex, highly integrated cascade of events, requiring the interactions of many cell types, including inflammatory cells, fibroblasts, keratinocytes and endothelial cells, as well as the involvement of growth factors and enzymes. However, several diseases such as diabetes, thermal injury and ischemia could lead to an impaired wound healing process characterized by wound hypoxia, high levels of oxygen radicals, reduced angiogenesis, decreased collagen synthesis and organization. Polydeoxyribonucleotide (PDRN) has been used to improve wound healing through local and systemic administration thanks to its ability to promote cell migration and growth, angiogenesis, and to reduce inflammation on impaired wound healing models in vitro, in vivo and clinical studies. In light of all these observations, the aim of this review is to provide a full overview of PDRN applications on skin regeneration. We reviewed papers published in the last 25 years on PubMed, inserting “polydeoxyribonucleotide and wound healing” as the main search term. All data obtained proved the ability of PDRN in promoting physiological tissue repair through adenosine A2A receptor activation and salvage pathway suggesting that PDRN has proven encouraging results in terms of healing time, wound regeneration and absence of side effects.

scholarly journals Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

2021 ◽  
Vol 22 (8) ◽  
pp. 4087
Author(s):  
Maria Quitério ◽  
Sandra Simões ◽  
Andreia Ascenso ◽  
Manuela Carvalheiro ◽  
Ana Paula Leandro ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
In Vitro Release ◽  
Peptide Hormone ◽  
Plga Nanoparticles ◽  
Wound Healing Process ◽  
Target Area ◽  
Encapsulation Process

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

scholarly journals Exosomal Vimentin from Adipocyte Progenitors Protects Fibroblasts against Osmotic Stress and Inhibits Apoptosis to Enhance Wound Healing

2021 ◽  
Vol 22 (9) ◽  
pp. 4678
Author(s):  
Sepideh Parvanian ◽  
Hualian Zha ◽  
Dandan Su ◽  
Lifang Xi ◽  
Yaming Jiu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Osmotic Stress ◽  
Mechanical Stress ◽  
Impaired Wound Healing ◽  
In Vivo Experiments ◽  
Adipocyte Progenitors ◽  
Osmotic Balance ◽  
Induced Apoptosis

Mechanical stress following injury regulates the quality and speed of wound healing. Improper mechanotransduction can lead to impaired wound healing and scar formation. Vimentin intermediate filaments control fibroblasts’ response to mechanical stress and lack of vimentin makes cells significantly vulnerable to environmental stress. We previously reported the involvement of exosomal vimentin in mediating wound healing. Here we performed in vitro and in vivo experiments to explore the effect of wide-type and vimentin knockout exosomes in accelerating wound healing under osmotic stress condition. Our results showed that osmotic stress increases the size and enhances the release of exosomes. Furthermore, our findings revealed that exosomal vimentin enhances wound healing by protecting fibroblasts against osmotic stress and inhibiting stress-induced apoptosis. These data suggest that exosomes could be considered either as a stress modifier to restore the osmotic balance or as a conveyer of stress to induce osmotic stress-driven conditions.

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