scholarly journals Dissolved oxygen from microalgae-gel patch promotes chronic wound healing in diabetes

2020 ◽  
Vol 6 (20) ◽  
pp. eaba4311 ◽  
Author(s):  
Huanhuan Chen ◽  
Yuhao Cheng ◽  
Jingrun Tian ◽  
Peizheng Yang ◽  
Xuerao Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Dissolved Oxygen ◽  
Oxygen Delivery ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Superior Performance ◽  
Gaseous Oxygen ◽  
Promote Cell Proliferation

Chronic wounds in diabetes undergo a lifetime risk of developing into diabetic foot ulcers. Oxygen is crucial to wound healing by regulating cell proliferation, migration, and neovascularization. However, current oxygen therapies, including hyperbaric oxygen (HBO) and topical gaseous oxygen (TGO), mainly employ gaseous oxygen delivery, which is much less effective in penetrating the skin. Here, we introduce an oxygen-producing patch, made of living microalgae hydrogel, which can produce dissolved oxygen. The superior performance of the patch that results from its dissolved oxygen delivery is >100-fold much more efficient than TGO penetrating the skin. Further experiments indicate that the patch could promote cell proliferation, migration, and tube formation in vitro, and improve chronic wound healing and the survival of skin grafts in diabetic mice. We believe that the microalgae-gel patch can provide continuous dissolved oxygen to improve chronic wound healing.

scholarly journals An EGF- and Curcumin-Co-Encapsulated Nanostructured Lipid Carrier Accelerates Chronic-Wound Healing in Diabetic Rats

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4610
Author(s):  
Hye-Jin Lee ◽  
Moses Jeong ◽  
Young-Guk Na ◽  
Sung-Jin Kim ◽  
Hong-Ki Lee ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Healing Process ◽  
Double Emulsion ◽  
Average Diameter ◽  
Diabetic Rats ◽  
Wound Healing Process ◽  
Nanostructured Lipid Carrier

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF–Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF–Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF–Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds.

scholarly journals Nanofiber-mediated sequential photothermal antibacteria and macrophage polarization for healing MRSA-infected diabetic wounds

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhou Xu ◽  
Bin Deng ◽  
Xuewen Wang ◽  
Jie Yu ◽  
Zhuobin Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Macrophage Polarization ◽  
In Vivo Studies ◽  
Promote Cell Proliferation ◽  
Diabetic Wound Healing ◽  
Mrsa Infection ◽  
Diabetic Wounds

Abstract Background Diabetic wound healing remains a challenge because of its susceptibility to drug-resistant bacterial infection and its persistent proinflammatory state. Switching from proinflammatory M1 macrophages (Mφs) to proregenerative M2 dominant Mφs in a timely manner accelerates wound healing by coordinating inflammatory, proliferative, and angiogenic processes. Methods We propose a sequential photothermal antibacterial and subsequent M2 Mφ polarization strategy based on nanofibers (NFs) consisting of polydopamine (PDA) coating on curcumin (Cur) nanocrystals to treat Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds. Results The PDA/Cur NFs showed excellent photothermal conversion and antibacterial effects due to the PDA shell under laser irradiation, consequently resulting in the release of the inner Cur with the ability to promote cell proliferation and reinforce the M2 Mφ phenotype in vitro. In vivo studies on MRSA-infected diabetic wounds showed that PDA/Cur NFs not only inhibited MRSA infection but also accelerated the wound regeneration process. Furthermore, the NFs displayed the ability to promote the M2 Mφ phenotype with enhanced collagen deposition, angiogenesis, and cell proliferation. Conclusion Overall, the NFs displayed great potential as promising therapeutics for healing infected diabetic wounds through a sequential photothermal antibacterial and M2 Mφ polarization strategy. Graphical abstract

scholarly journals Fibrin-Modified Cellulose as a Promising Dressing for Accelerated Wound Healing

Materials ◽  
2018 ◽  
Vol 11 (11) ◽  
pp. 2314 ◽  
Author(s):  
Marketa Bacakova ◽  
Julia Pajorova ◽  
Tomas Sopuch ◽  
Lucie Bacakova
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Wound Dressing ◽  
Chronic Wounds ◽  
Cell Attachment ◽  
Cellulose Fibers ◽  
Dermal Fibroblasts ◽  
Hydroxyl Groups ◽  
Structural Morphology

Dermal injuries and chronic wounds usually regenerate with scar formation. Successful treatment without scarring might be achieved by pre-seeding a wound dressing with cells. We aimed to prepare a wound dressing fabricated from sodium carboxymethylcellulose (Hcel® NaT), combined with fibrin and seeded with dermal fibroblasts in vitro. We fabricated the Hcel® NaT in a porous and homogeneous form (P form and H form, respectively) differing in structural morphology and in the degree of substitution of hydroxyl groups. Each form of Hcel® NaT was functionalized with two morphologically different fibrin structures to improve cell adhesion and proliferation, estimated by an MTS assay. Fibrin functionalization of the Hcel® NaT strongly enhanced colonization of the material with human dermal fibroblasts. Moreover, the type of fibrin structures influenced the ability of the cells to adhere to the material and proliferate on it. The fibrin mesh filling the void spaces between cellulose fibers better supported cell attachment and subsequent proliferation than the fibrin coating, which only enwrapped individual cellulose fibers. On the fibrin mesh, the cell proliferation activity on day 3 was higher on the H form than on the P form of Hcel® NaT, while on the fibrin coating, the cell proliferation on day 7 was higher on the P form. The Hcel® NaT wound dressing functionalized with fibrin, especially when in the form of a mesh, can accelerate wound healing by supporting fibroblast adhesion and proliferation.

scholarly journals Electrical Stimulation to Enhance Wound Healing

2021 ◽  
Vol 12 (2) ◽  
pp. 40
Author(s):  
Saranya B. Rajendran ◽  
Kirsty Challen ◽  
Karen L. Wright ◽  
John G. Hardy
Keyword(s):  
Wound Healing ◽  
Electrical Stimulation ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Financial Burden ◽  
Cochrane Library ◽  
Publication Date ◽  
Pulsed Current ◽  
Fibroblast Migration

Electrical stimulation (ES) can serve as a therapeutic modality accelerating the healing of wounds, particularly chronic wounds which have impaired healing due to complications from underlying pathology. This review explores how ES affects the cellular mechanisms of wound healing, and its effectiveness in treating acute and chronic wounds. Literature searches with no publication date restrictions were conducted using the Cochrane Library, Medline, Web of Science, Google Scholar and PubMed databases, and 30 full-text articles met the inclusion criteria. In vitro and in vivo experiments investigating the effect of ES on the general mechanisms of healing demonstrated increased epithelialization, fibroblast migration, and vascularity around wounds. Six in vitro studies demonstrated bactericidal effects upon exposure to alternating and pulsed current. Twelve randomized controlled trials (RCTs) investigated the effect of pulsed current on chronic wound healing. All reviewed RCTs demonstrated a larger reduction in wound size and increased healing rate when compared to control groups. In conclusion, ES therapy can contribute to improved chronic wound healing and potentially reduce the financial burden associated with wound management. However, the variations in the wound characteristics, patient demographics, and ES parameters used across studies present opportunities for systematic RCT studies in the future.

scholarly journals Development of Cephradine-Loaded Gelatin/Polyvinyl Alcohol Electrospun Nanofibers for Effective Diabetic Wound Healing: In-Vitro and In-Vivo Assessments

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 349
Author(s):  
Anam Razzaq ◽  
Zaheer Ullah Khan ◽  
Aasim Saeed ◽  
Kiramat Ali Shah ◽  
Naveed Ullah Khan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Polyvinyl Alcohol ◽  
Mtt Assay ◽  
Chronic Wound ◽  
Drug Loading ◽  
Group Identification ◽  
Wound Infections ◽  
Diabetic Wound

Diabetic wound infections caused by conventional antibiotic-resistant Staphylococcus aureus strains are fast emerging, leading to life-threatening situations (e.g., high costs, morbidity, and mortality) associated with delayed healing and chronic inflammation. Electrospinning is one of the most widely used techniques for the fabrication of nanofibers (NFs), induced by a high voltage applied to a drug-loaded polymer solution. Particular attention is given to electrospun NFs for pharmaceutical applications (e.g., original drug delivery systems) and tissue regeneration (e.g., as tissue scaffolds). However, there is a paucity of reports related to their application in diabetic wound infections. Therefore, we prepared eco-friendly, biodegradable, low-immunogenic, and biocompatible gelatin (GEL)/polyvinyl alcohol (PVA) electrospun NFs (BNFs), in which we loaded the broad-spectrum antibiotic cephradine (Ceph). The resulting drug-loaded NFs (LNFs) were characterized physically using ultraviolet-visible (UV-Vis) spectrophotometry (for drug loading capacity (LC), drug encapsulation efficiency (EE), and drug release kinetics determination), thermogravimetric analysis (TGA) (for thermostability evaluation), scanning electron microscopy (SEM) (for surface morphology analysis), and Fourier-transform infrared spectroscopy (FTIR) (for functional group identification). LNFs were further characterized biologically by in-vitro assessment of their potency against S. aureus clinical strains (N = 16) using the Kirby–Bauer test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, by ex-vivo assessment to evaluate their cytotoxicity against primary human epidermal keratinocytes using MTT assay, and by in-vivo assessment to estimate their diabetic chronic wound-healing efficiency using NcZ10 diabetic/obese mice (N = 18). Thin and uniform NFs with a smooth surface and standard size (<400 nm) were observed by SEM at the optimized 5:5 (GEL:PVA) volumetric ratio. FTIR analyses confirmed the drug loading into BNFs. Compared to free Ceph, LNFs were significantly more thermostable and exhibited sustained/controlled Ceph release. LNFs also exerted a significantly stronger antibacterial activity both in-vitro and in-vivo. LNFs were significantly safer and more efficient for bacterial clearance-induced faster chronic wound healing. LNF-based therapy could be employed as a valuable dressing material to heal S. aureus-induced chronic wounds in diabetic subjects.

scholarly journals Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard

2021 ◽  
Vol 95 (2) ◽  
pp. 727-747
Author(s):  
Simone Rothmiller ◽  
Niklas Jäger ◽  
Nicole Meier ◽  
Thimo Meyer ◽  
Adrian Neu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Alkylating Agent ◽  
Chronic Wounds ◽  
Sulfur Mustard ◽  
Morphological Changes ◽  
Human Mesenchymal Stem Cells ◽  
Age Related

AbstractWound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases.

scholarly journals HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/β-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor

2018 ◽  
Vol 19 (10) ◽  
pp. 3153 ◽  
Author(s):  
J. Muñoz-Bello ◽  
Leslie Olmedo-Nieva ◽  
Leonardo Castro-Muñoz ◽  
Joaquín Manzo-Merino ◽  
Adriana Contreras-Paredes ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Promote Cell Proliferation ◽  
E6 And E7 ◽  
Hpv 18

The Wnt/β-catenin signaling pathway regulates cell proliferation and differentiation and its aberrant activation in cervical cancer has been described. Persistent infection with high risk human papillomavirus (HR-HPV) is the most important factor for the development of this neoplasia, since E6 and E7 viral oncoproteins alter cellular processes, promoting cervical cancer development. A role of HPV-16 E6 in Wnt/β-catenin signaling has been proposed, although the participation of HPV-18 E6 has not been previously studied. The aim of this work was to investigate the participation of HPV-18 E6 and E6*I, in the regulation of the Wnt/β-catenin signaling pathway. Here, we show that E6 proteins up-regulate TCF-4 transcriptional activity and promote overexpression of Wnt target genes. In addition, it was demonstrated that E6 and E6*I bind to the TCF-4 (T cell factor 4) and β-catenin, impacting TCF-4 stabilization. We found that both E6 and E6*I proteins interact with the promoter of Sp5, in vitro and in vivo. Moreover, although differences in TCF-4 transcriptional activation were found among E6 intratype variants, no changes were observed in the levels of regulated genes. Furthermore, our data support that E6 proteins cooperate with β-catenin to promote cell proliferation.

scholarly journals Influence of Antihypertensive and Antidiabetic Drugs on Wound Healing – Essentials of a Systematic In-Vitro Study

2019 ◽  
Vol 4 (1) ◽  
pp. 01-04
Author(s):  
Ewa K. Stuermer
Keyword(s):  
Wound Healing ◽  
Life Style ◽  
Chronic Wounds ◽  
In Vitro Study ◽  
Antidiabetic Drugs ◽  
Vitro Study ◽  
Lower Limbs ◽  
Nerve Lesions

Due to the increasing prevalence of so called "life style diseases", such as diabetes, obesity or hypertension, the number of associated vascular and nerve lesions increases. In the lower limbs in particular, bagatelle trauma causes wounds that lead to wound healing disorders and chronic wounds

scholarly journals Systemic and topical administration of spermidine accelerates skin wound healing

2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Wound Repair ◽  
Healing Process ◽  
Topical Administration ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

scholarly journals The Activity of Combination of Hydrolyzed Virgin Coconut Oil and Chitosan Toward Wound Healing Parameters on NIH 3T3 Cells Using in Vitro Methods

1970 ◽  
Vol 7 (3) ◽  
pp. 14-19 ◽  
Author(s):  
Hekdin Marsius Sipayung ◽  
Jansen Silalahi ◽  
Yuandani Y
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Protein Expression ◽  
Scratch Wound ◽  
Cell Proliferation Activity ◽  
Proliferation Activity ◽  
Cox 2 ◽  
Nih 3T3 ◽  
Vegf Protein

Objectives: The objective of this study was to investigate the activity of combination of hydrolyzed VCO (HVCO) and chitosan on NIH 3T3 cell proliferation activity, NIH 3T3 cell migration, COX-2 and VEGF protein expression. Design: In vitro cytotoxic assay was determined by MTT (MicrocultureTetrazoliumTehnique) assay, cell proliferation activity was measured by calculating cell viability incubated 24 hours, 48 hours and 72 hours, wound closure percentage was tested by scratch wound healing method, expression of COX-2 protein and VEGF protein were measured by immunocytochemical method. Interventions: The variable that was intervened in this study was the concentration of HVCO and chitosan. Main Outcome Measures: The main measurements carried out in this study were the absorbance value of HVCO and chitosan which was converted into viability cell, proliferation activity, percentage of wound closure, and percentage of COX-2 and VEGF protein expression. Results: Cytotoxic activity of HVCO and chitosan resulted the best concentration at 31.25 μg/ml, scratch wound healing assay from a combination HVCO and chitosan resulted the best migration of fibroblast cells at a ratio of 1:1 with HVCO 62.5 μg/ml and chitosan 62.5 μg/ml, combination of HVCO 62.5 μg/ml and chitosan 62.5 μg/ml (1:1) increased expression of COX-2 and VEGF. Conclusion: Combination of HVCO and chitosan could increase NIH 3T3 cell migration, COX-2 and VEGF protein expression. Combination of HVCO and chitosan had better wound healing activity in vitro than single use. Keywords: Rhizomucor miehei, viability, proliferation, migration, expression

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