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Chen C, Yang J, Shang R, Tang Y, Cai X, Chen Y, Liu Z, Hu W, Zhang W, Zhang X, Huang Y, Hu X, Yin W, Lu Q, Sheng H, Fan D, Ju Z, Luo G, He W. Orchestration of Macrophage Polarization Dynamics by Fibroblast-Secreted Exosomes during Skin Wound Healing. J Invest Dermatol 2025; 145:171-184.e6. [PMID: 38838771 DOI: 10.1016/j.jid.2024.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 04/30/2024] [Accepted: 05/04/2024] [Indexed: 06/07/2024]
Abstract
Macrophages undertake pivotal yet dichotomous functions during skin wound healing, mediating both early proinflammatory immune activation and late anti-inflammatory tissue remodeling processes. The timely phenotypic transition of macrophages from inflammatory M1 to proresolving M2 activation states is essential for efficient healing. However, the endogenous mechanisms calibrating macrophage polarization in accordance with the evolving tissue milieu remain undefined. In this study, we reveal an indispensable immunomodulatory role for fibroblast-secreted exosomes in directing macrophage activation dynamics. Fibroblast-derived exosomes permitted spatiotemporal coordination of macrophage phenotypes independent of direct intercellular contact. Exosomes enhanced macrophage sensitivity to both M1 and M2 polarizing stimuli, yet they also accelerated timely switching from M1 to M2 phenotypes. Exosome inhibition dysregulated macrophage responses, resulting in aberrant inflammation and impaired healing, whereas provision of exogenous fibroblast-derived exosomes corrected defects. Topical application of fibroblast-derived exosomes onto chronic diabetic wounds normalized dysregulated macrophage activation to resolve inflammation and restore productive healing. Our findings elucidate fibroblast-secreted exosomes as remote programmers of macrophage polarization that calibrate immunological transitions essential for tissue repair. Harnessing exosomes represents a previously unreported approach to steer productive macrophage activation states with immense therapeutic potential for promoting healing in chronic inflammatory disorders.
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Affiliation(s)
- Cheng Chen
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Jiacai Yang
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Ruoyu Shang
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Yuanyang Tang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xin Cai
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Yunxia Chen
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Zhihui Liu
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Wengang Hu
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Weiguang Zhang
- Department of Intensive Care, Southwest Hospital, Army Medical University, Chongqing, China
| | - Xiaorong Zhang
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Yong Huang
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Xiaohong Hu
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Wenjing Yin
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China; Academy of Biological Engineering, Chongqing University, Chongqing, China
| | - Qudong Lu
- Department of Urology, Army 73rd Group Military Hospital, Xiamen, China
| | - Hao Sheng
- Department of Urology, The Second Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Dejiang Fan
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China
| | - Zhenyu Ju
- Key Laboratory of Regenerative Medicine of Ministry of Education, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China
| | - Gaoxing Luo
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China.
| | - Weifeng He
- Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing, China.
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Anuradha U, Bhavana V, Chary PS, Rajana N, Parida KK, Kalia NP, Khatri DK, Mehra NK. Thymoquinone loaded nanoemulgel in streptozotocin induced diabetic wound. Nanomedicine (Lond) 2024; 19:2577-2604. [PMID: 39569618 DOI: 10.1080/17435889.2024.2422805] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 10/25/2024] [Indexed: 11/22/2024] Open
Abstract
Aim: To treat diabetic wound healing with a novel Thymoquinone (TQ) loaded nanoformulation by using combination of essentials oils.Methods: TQ nanoemulsion (NE) was developed with seabuckthorn & lavender essential oils by phase inversion method and mixture design. Further, DIAGEL is obtained by incorporating NE into 1% carbopol®934. Furthermore, particle size, polydispersity index, thermodynamic stability studies, rheology, spreadability, drug content, in-vitro drug release, ex-vivo permeation, anti-oxidant assay, antimicrobial studies, angioirritance, HAT-CAM assay, in-vitro and in-vivo studies were determined.Results: NE has a particle size of 17.79 ± 0.61 nm, 0.206 ± 0.012 PDI & found to be thermodynamically stable. DIAGEL exhibited pseudoplastic behavior, sustained drug release, better permeation of TQ and a drug content of 98.54 ± 0.08%. DIAGEL stored for 6 months at room temperature and 2-8°C showed no degradation. Further, an improved angiogenesis, absence of angio-irritancy, remarkable antioxidant and antimicrobial activities against Candida albicans & S. aureus were observed. Cytotoxicity analysis revealed nearly 2.28 -folds higher IC50 value than drug solution. Furthermore, inflammatory mediators were reduced in DIAGEL treated animal groups. The histopathological studies confirmed skin healing with regeneration and granulation of tissue.Conclusion: The novel formulation has strong anti-inflammatory, angiogenesis, antioxidant and appreciable diabetic wound healing properties.
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Affiliation(s)
- Urati Anuradha
- Department of Biological Sciences, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Telangana, 500037, India
| | - Valamla Bhavana
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Telangana, 500037, India
| | - Padakanti Sandeep Chary
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Telangana, 500037, India
| | - Naveen Rajana
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Telangana, 500037, India
| | - Kishan Kumar Parida
- Department of Biological Sciences, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Telangana, 500037, India
| | - Nitin Pal Kalia
- Department of Biological Sciences, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Telangana, 500037, India
| | - Dharmendra Kumar Khatri
- Department of Pharmacology, NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, 303121, India
| | - Neelesh Kumar Mehra
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, Telangana, 500037, India
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Sultana A, Borgohain R, Rayaji A, Saha D, Kumar Das B. Promising Phytoconstituents in Diabetes-related Wounds: Mechanistic Insights and Implications. Curr Diabetes Rev 2024; 21:e270224227477. [PMID: 38424430 DOI: 10.2174/0115733998279112240129074457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 01/05/2024] [Accepted: 01/16/2024] [Indexed: 03/02/2024]
Abstract
BACKGROUND The onset of diabetes mellitus (DM), a metabolic disorder characterized by high blood glucose levels and disrupted glucose metabolism, results in 20% of people with diabetes suffering from diabetes-related wounds worldwide. A minor wound, such as a cut or abrasion, can lead to infections and complications in diabetic patients. We must understand the mechanism/s contributing to this delayed wound healing to develop effective prevention strategies. The potential benefits of bioactive phytochemicals for diabetic wound healing have been reported in numerous studies. METHOD A bioactive compound may have multiple actions, including antioxidants, antiinflammatory, antimicrobial, and angiogenesis. Compounds derived from these plants have shown promising results in wound healing, inflammation reduction, collagen synthesis, and neovascularization improvement. RESULTS Consequently, this review provides an update to our understanding of how phytoconstituents promote wound healing in diabetics. A thorough literature review was conducted on diabetes, wound healing, and phytoconstituents for this study. Only English publications until June 2023 were included in the search, which used multiple search engines and the main keywords. Summing up, phytochemical-based interventions might improve the quality of life for diabetics by improving wound healing. CONCLUSION However, to fully understand the efficacy and safety of these phytochemicals in managing diabetic wounds, more research and clinical trials are needed.
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Affiliation(s)
- Arjina Sultana
- Department of Pharmacology, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Azara, Guwahati 781017, Assam, India
| | - Ranadeep Borgohain
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Azara, Guwahati 781017, Assam, India
| | - Ashwini Rayaji
- Department of Pharmaceutical Chemistry, KRE's Karnataka College of Pharmacy, Bidar 585403, Karnataka, India
| | - Dipankar Saha
- Department of Pharmacology, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Azara, Guwahati 781017, Assam, India
| | - Bhrigu Kumar Das
- Department of Pharmacology, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Azara, Guwahati 781017, Assam, India
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Raktoe R, Kwee AKAL, Rietveld M, Marsidi N, Genders R, Quint K, van Doorn R, van Zuijlen P, Ghalbzouri AEL. Mimicking fat grafting of fibrotic scars using 3D-organotypic skin cultures. Exp Dermatol 2023; 32:1752-1762. [PMID: 37515391 DOI: 10.1111/exd.14893] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 07/10/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023]
Abstract
Wound healing of deep burn injuries is often accompanied by severe scarring, such as hypertrophic scar (HTS) formation. In severe burn wounds, where the subcutis is also damaged, the scars adhere to structures underneath, resulting in stiffness of the scar and impaired motion. Over the recent years, a promising solution has emerged: autologous fat grafting, also known as lipofilling. Previous clinical reports have shown that the anti-fibrotic effect has been attributed to the presence of adipose-derived stromal cells (ADSC). In the proposed study, we aim to investigate the effect of fat grafting in 3D organotypic skin cultures mimicking an HTS-like environment. To this end, organotypic skin cultures were embedded with normal skin fibroblasts (NF) or HTS-derived fibroblasts with or without incorporation of human adipose subcutaneous tissue (ADT) and one part was thermally wounded to examine their effect on epithelialization. The developed skin cultures were analysed on morphology and protein level. Analysis revealed that ADT-containing organotypic skin cultures comprise an improved epidermal homeostasis, and a fully formed basement membrane, similar to native human skin (NHS). Furthermore, the addition of ADT significantly reduced myofibroblast presence, which indicates its anti-fibrotic effect. Finally, re-epithelialization measurements showed that ADT reduced re-epithelialization in skin cultures embedded with NFs, whereas HTS-fibroblast-embedded skin cultures showed complete wound closure. In conclusion, we succeeded in developing a 3D organotypic HTS-skin model incorporated with subcutaneous tissue that allows further investigation on the molecular mechanism of fat grafting.
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Affiliation(s)
- Rajiv Raktoe
- Department of Dermatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Anastasia K A L Kwee
- Department of Dermatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Marion Rietveld
- Department of Dermatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Nick Marsidi
- Department of Dermatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Roel Genders
- Department of Dermatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
- Department of Dermatology, Roosevelt Clinics, Leiden, The Netherlands
| | - Koen Quint
- Department of Dermatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
- Department of Dermatology, Roosevelt Clinics, Leiden, The Netherlands
| | - Remco van Doorn
- Department of Dermatology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands
| | - Paul van Zuijlen
- Burn Centre, Red Cross Hospital, Beverwijk, The Netherlands
- Department of Plastic and Reconstructive Surgery, Red Cross Hospital, Beverwijk, The Netherlands
- Department of Plastic, Reconstructive and Hand Surgery, Amsterdam Movement Sciences, Amsterdam UMC (location VUmc), Amsterdam, The Netherlands
- Pediatric Surgical Centre, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands
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Dehghanpour HR, Parvin P, Ganjali P, Golchini A, Eshghifard H, Heidari O. Evaluation of photobiomodulation effect on cesarean-sectioned wound healing: a clinical study. Lasers Med Sci 2023; 38:171. [PMID: 37526765 DOI: 10.1007/s10103-023-03774-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 04/05/2023] [Indexed: 08/02/2023]
Abstract
The effects of low-level laser on the wound healing and burn injuries have been previously examined to demonstrate some satisfactory results. Despite there are a few articles available to study photobiomodulation (PBM) effects on the pain relief of cesarean sectioned wound, however no systematic examination has been carried out so far regarding its healing. Here, the aim of this clinical study was to evaluate PBM effect on the cesarean-sectioned wound healing. PBM effects of semiconductor lasers are investigated at 658 and 660 nm with 100, 150 and 350 mW output powers on 40 patients. Due to the global increasing number of cesarean sections, we have decided to investigate the effect of laser as a reliable technique to recover the wounds fast. We considered women as the target group who had their first delivery giving the birth of their children by cesarean section. We selected patients are who treated by laser therapy using indium gallium aluminum phosphide (InGaAlP) semiconductor linear scanning type with beam cross section of 12 cm2 and the output power of 100 mW at 658 nm exposing a therapeutic dose of 2 J/cm2. The purpose is to accelerate the healing process of the wounds after delivery as an intervention group against the people who chose the conventional methods (using ointments, pills, etc.) to heal their cesarean sectioned wounds as the control group. Regarding the wounds of these two groups, the questionnaires were filled by patients to assess the severity of pain from visual analogue scale (VAS) based on the healing of wounds from redness, edema, ecchymosis, discharge, and distance between the two edges of the wound (REEDA) scale in the early hours after surgery and the post-treatment follow-up on the third, seventh, and the tenth days. The data collected by these questionnaires were analyzed using statistical package for social science)SPSS( as a statistical software to give out the comparative histograms. This study reports a clinical examination of PBM under intervention group of 40 patients ranging 18-40 years old with body mass index (BMI) of 29-36, during post-cesarean surgery to elucidate successful healing of the wounds and scars against conventional methods which considered as control group. Comparison of mean REEDA scores on the third day (p = 0.035), seventh day (p = 0.03), and tenth day (p = 0.02) after delivery exhibits that the two groups benefit a statistically significant difference with each other. For instance, the mean wound healing score in the intervention group was almost half of the mean wound healing score on the tenth day in the control group (1.09 ± 0.586 vs. 2.25 ± 0.422). The post-cesarean follow-up indicates that the patients treated by the laser therapy (intervention group) encounter better recovery than the control group.
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Affiliation(s)
| | - Parviz Parvin
- Physics Department, Amirkabir University of Technology, P.O. Box, Tehran, 15875-4413, Iran
| | - Parvaneh Ganjali
- Department of Physics, Tafresh University, Tafresh, 3951879611, Iran
| | | | | | - Omid Heidari
- Physics Department, Amirkabir University of Technology, P.O. Box, Tehran, 15875-4413, Iran
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Subramanian S, Duraipandian C, Alsayari A, Ramachawolran G, Wong LS, Sekar M, Gan SH, Subramaniyan V, Seethalakshmi S, Jeyabalan S, Dhanasekaran S, Chinni SV, Mat Rani NNI, Wahab S. Wound healing properties of a new formulated flavonoid-rich fraction from Dodonaea viscosa Jacq. leaves extract. Front Pharmacol 2023; 14:1096905. [PMID: 36817128 PMCID: PMC9932054 DOI: 10.3389/fphar.2023.1096905] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 01/18/2023] [Indexed: 02/05/2023] Open
Abstract
Background: Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as "Sinatha," and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds. Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds. Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01). Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.
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Affiliation(s)
- Shanthi Subramanian
- Department of Pharmacognosy, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai, Tamilnadu, India
| | - Chamundeeswari Duraipandian
- Department of Pharmacognosy, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai, Tamilnadu, India
| | - Abdulrhman Alsayari
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
- Complementary and Alternative Medicine Unit, King Khalid University, Abha, Saudi Arabia
| | | | - Ling Shing Wong
- Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia
| | - Mahendran Sekar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia
| | - Siew Hua Gan
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
| | | | - S Seethalakshmi
- Department of Pharmacology, ESIC Medical College and PGIMSR, Chennai, Tamilnadu, India
| | - Srikanth Jeyabalan
- Department of Pharmacology, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai, Tamilnadu, India
| | | | - Suresh V. Chinni
- Department of Biochemistry, Faculty of Medicine, Bioscience, and Nursing, MAHSA University, Kuala Lumpur, Malaysia
- Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | - Nur Najihah Izzati Mat Rani
- Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia
| | - Shadma Wahab
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
- Complementary and Alternative Medicine Unit, King Khalid University, Abha, Saudi Arabia
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Gao J, Wang J, Chen P, Ding P, Tian L, Liang B, Shi Z. The Effect of Qingre Huayu Recipe on Wound Healing after Anal Fistulotomy in Sprague-Dawley Rats. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:9397478. [PMID: 35495890 PMCID: PMC9042638 DOI: 10.1155/2022/9397478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/16/2022] [Accepted: 02/25/2022] [Indexed: 12/29/2022]
Abstract
Anal fistula is a common anorectal disease. At present, most scholars believe that its pathogenesis is related to anal gland infection. Anal fistula cannot heal on its own after the onset and must be treated surgically. The wound of anal fistula surgery is open and polluted, and it belongs to three types of three-stage healing; it is the most difficult to heal among all surgical incisions, with a long course of disease, a lot of exudation, and pain for the patient; traditional Chinese medicine has rich experience in the treatment of postoperative wound healing of anal fistula. The study aimed to evaluate the mechanism of Qingre Huayu (QRHY) Recipe on wound healing after fistulotomy on SD rats. SD rats (n = 72) were randomized into three groups post-anorectal surgery. The rats in the positive control group were given potassium permanganate (PP), treatment group were given QRHY, and trauma model group were given 0.9% normal salinity. The changes in wound secretion, granulated tissue, and epithelium tissue were observed, and wound healing rates were evaluated by the discrepancies in wound area. HE and Masson's staining as well as transmission electron microscopy were also performed. The localization as well as the measurement of Ang1, Src, and VE cadherin expression in each group adopted real-time PCR, western blot, and immunohistochemistry (IHC) assays. Statistically higher wound healing rates were observed in QRHY group on days 3, 7, and 14 compared with other groups. Histological analyses showed highly significant increase in collagen and fibroblasts, less inflammatory cells, and vascular endothelial permeability in QRHY rats. The transmission electron microscopy revealed that the intact structure of tight junctions in endothelial cells and well-organized collagen and VE-cadherin, Ang1, and Tie-2 were upregulated by QRHY, while Src was inhibited. This study showed that QRHY can promote wound healing after anal fistulas.
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Affiliation(s)
- Jiazhi Gao
- Department of Proctology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 Lanxi Road, Shanghai 200333, China
| | - Jiandong Wang
- Department of Proctology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 Lanxi Road, Shanghai 200333, China
| | - Ping Chen
- Department of Proctology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 Lanxi Road, Shanghai 200333, China
| | - Peilin Ding
- Department of Proctology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 Lanxi Road, Shanghai 200333, China
| | - Liang Tian
- Department of Proctology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 Lanxi Road, Shanghai 200333, China
| | - Biao Liang
- Department of Proctology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 Lanxi Road, Shanghai 200333, China
| | - Zhan Shi
- Department of Proctology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164 Lanxi Road, Shanghai 200333, China
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Wang J, He J, Zhu M, Han Y, Yang R, Liu H, Xu X, Chen X. Cellular Heterogeneity and Plasticity of Skin Epithelial Cells in Wound Healing and Tumorigenesis. Stem Cell Rev Rep 2022; 18:1912-1925. [PMID: 35143021 PMCID: PMC9391238 DOI: 10.1007/s12015-021-10295-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/27/2021] [Indexed: 12/20/2022]
Abstract
Cellular differentiation, the fundamental hallmark of cells, plays a critical role in homeostasis. And stem cells not only regulate the process where embryonic stem cells develop into a complete organism, but also replace ageing or damaged cells by proliferation, differentiation and migration. In characterizing distinct subpopulations of skin epithelial cells, stem cells show large heterogeneity and plasticity for homeostasis, wound healing and tumorigenesis. Epithelial stem cells and committed progenitors replenish each other or by themselves owing to the remarkable plasticity and heterogeneity of epidermal cells under certain circumstance. The development of new assay methods, including single-cell RNA sequence, lineage tracing assay, intravital microscopy systems and photon-ablation assay, highlight the plasticity of epidermal stem cells in response to injure and tumorigenesis. However, the critical mechanisms and key factors that regulate cellular plasticity still need for further exploration. In this review, we discuss the recent insights about the heterogeneity and plasticity of epithelial stem cells in homeostasis, wound healing and skin tumorigenesis. Understanding how stem cells collaborate together to repair injury and initiate tumor will offer new solutions for relevant diseases. Schematic abstract of cellular heterogeneity and plasticity of skin epithelial cells in wound healing and tumorigenesis.
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Affiliation(s)
- Jingru Wang
- Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.,Department of Burn Surgery, First People's Hospital of Foshan, Foshan, China
| | - Jia He
- Department of Burn Surgery, First People's Hospital of Foshan, Foshan, China.,School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, China
| | - Meishu Zhu
- Department of Burn and Plastic Surgery, Second People's Hospital of Shenzhen, First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
| | - Yan Han
- The Yonghe Medical Group Limited Company, George Town, Cayman Islands
| | - Ronghua Yang
- Department of Burn Surgery, First People's Hospital of Foshan, Foshan, China
| | - Hongwei Liu
- Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
| | - Xuejuan Xu
- Endocrinology Department, First People's Hospital of Foshan, Foshan, China.
| | - Xiaodong Chen
- Department of Burn Surgery, First People's Hospital of Foshan, Foshan, China.
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9
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Elloumi W, Mahmoudi A, Ortiz S, Boutefnouchet S, Chamkha M, Sayadi S. Wound healing potential of quercetin-3-O-rhamnoside and myricetin-3-O-rhamnoside isolated from Pistacia lentiscus distilled leaves in rats model. Biomed Pharmacother 2022; 146:112574. [PMID: 35062055 DOI: 10.1016/j.biopha.2021.112574] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 12/14/2021] [Accepted: 12/19/2021] [Indexed: 11/02/2022] Open
Abstract
The development of bioproducts able to accelerate wound healing is an important topic in biomedicine. In the current study, Pistacia lentiscus distilled leaves (PDL) extract and its two isolated glycosylated flavonoids, myricetin-3-O-rhamnoside (MM) and quercetin-3-O-rhamnoside (QM), were evaluated for their wound healing activity, including evaluation of wound closure, revascularization, wound re-epithelialization, fibroblast proliferation, and collagen deposition on rat skin samples. Moreover, hydroxyproline content, C-reactive protein (CRP) level, and immunohistochemistry study were evaluated on blood and tissues collected from rats on day 14 post-wounding. Results showed that the topical application of PDL (at a concentration of 20 mg/ml) (PDL 20), MM, and QM increased wound healing and decreased inflammatory cells infiltration compared to the negative control group. Moreover, the cutaneous wound tissues treated with PDL 20, MM, and QM exhibited significantly higher hydroxyproline content than the negative control group, which means a high collagen biosynthesis in wound tissues. Indeed, the level of the inflammatory protein CRP is significantly lower in groups treated with MM and QM than in the negative control group. Also, the expression of the pro-inflammatory factor TNF-α and the angiogenesis marker CD-31 in PDL 20, MM, and QM treated groups is lower than in the negative control group. Moreover, MM, and QM induced a good elastase inhibition at 100 µg/ml compared to the standard epigallocatechin gallate. Therefore, PDL 20, MM, and QM could be used as effective cutaneous wound healing agents.
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Affiliation(s)
- Wiem Elloumi
- Laboratory of Environmental Bioprocesses, Center of Biotechnology of Sfax, University of Sfax, PO Box 1177, 3018 Sfax, Tunisia
| | - Asma Mahmoudi
- Laboratory of Environmental Bioprocesses, Center of Biotechnology of Sfax, University of Sfax, PO Box 1177, 3018 Sfax, Tunisia
| | - Sergio Ortiz
- Laboratoire de Pharmacognosie, UMR CNRS 8638 COMETE, Faculté de Pharmacie de Paris, Université Paris-Descartes, 4, av. de l'Observatoire, 75006 Paris, France
| | - Sabrina Boutefnouchet
- Laboratoire de Pharmacognosie, UMR CNRS 8638 COMETE, Faculté de Pharmacie de Paris, Université Paris-Descartes, 4, av. de l'Observatoire, 75006 Paris, France
| | - Mohamed Chamkha
- Laboratory of Environmental Bioprocesses, Center of Biotechnology of Sfax, University of Sfax, PO Box 1177, 3018 Sfax, Tunisia
| | - Sami Sayadi
- Biotechnology Program, Center for Sustainable Development, College of Arts and Sciences, Qatar University, Doha 2713, Qatar.
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10
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Del Amo C, Perez-Valle A, Perez-Garrastachu M, Jauregui I, Andollo N, Arluzea J, Guerrero P, de la Caba K, Andia I. Plasma-Based Bioinks for Extrusion Bioprinting of Advanced Dressings. Biomedicines 2021; 9:1023. [PMID: 34440227 PMCID: PMC8392180 DOI: 10.3390/biomedicines9081023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/03/2021] [Accepted: 08/06/2021] [Indexed: 12/04/2022] Open
Abstract
Extrusion bioprinting based on the development of novel bioinks offers the possibility of manufacturing clinically useful tools for wound management. In this study, we show the rheological properties and printability outcomes of two advanced dressings based on platelet-rich plasma (PRP) and platelet-poor plasma (PPP) blended with alginate and loaded with dermal fibroblasts. Measurements taken at 1 h, 4 days, and 18 days showed that both the PRP- and PPP-based dressings retain plasma and platelet proteins, which led to the upregulation of angiogenic and immunomodulatory proteins by embedded fibroblasts (e.g., an up to 69-fold increase in vascular endothelial growth factor (VEGF), an up to 188-fold increase in monocyte chemotactic protein 1 (MCP-1), and an up to 456-fold increase in hepatocyte growth factor (HGF) 18 days after printing). Conditioned media harvested from both PRP and PPP constructs stimulated the proliferation of human umbilical vein endothelial cells (HUVECs), whereas only those from PRP dressings stimulated HUVEC migration, which correlated with the VEGF/MCP-1 and VEGF/HGF ratios. Similarly, the advanced dressings increased the level of interleukin-8 and led to a four-fold change in the level of extracellular matrix protein 1. These findings suggest that careful selection of plasma formulations to fabricate wound dressings can enable regulation of the molecular composition of the microenvironment, as well as paracrine interactions, thereby improving the clinical potential of dressings and providing the possibility to tailor each composition to specific wound types and healing stages.
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Affiliation(s)
- Cristina Del Amo
- Regenerative Therapies, Bioprinting Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; (C.D.A.); (A.P.-V.); (I.J.)
| | - Arantza Perez-Valle
- Regenerative Therapies, Bioprinting Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; (C.D.A.); (A.P.-V.); (I.J.)
| | - Miguel Perez-Garrastachu
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country, UPV/EHU, 48940 Leioa, Spain; (M.P.-G.); (N.A.); (J.A.)
| | - Ines Jauregui
- Regenerative Therapies, Bioprinting Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; (C.D.A.); (A.P.-V.); (I.J.)
| | - Noelia Andollo
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country, UPV/EHU, 48940 Leioa, Spain; (M.P.-G.); (N.A.); (J.A.)
- BEGIKER, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
| | - Jon Arluzea
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country, UPV/EHU, 48940 Leioa, Spain; (M.P.-G.); (N.A.); (J.A.)
| | - Pedro Guerrero
- BIOMAT Research Group, Escuela de Ingeniería de Gipuzkoa Donostia-San Sebastián, University of the Basque Country (UPV/EHU), 20018 Donostia-San Sebastian, Spain; (P.G.); (K.d.l.C.)
- BCMaterials, Basque Center for Materials, Applications and Nanostructures, UPV/EHU Science Park, 48940 Leioa, Spain
| | - Koro de la Caba
- BIOMAT Research Group, Escuela de Ingeniería de Gipuzkoa Donostia-San Sebastián, University of the Basque Country (UPV/EHU), 20018 Donostia-San Sebastian, Spain; (P.G.); (K.d.l.C.)
- BCMaterials, Basque Center for Materials, Applications and Nanostructures, UPV/EHU Science Park, 48940 Leioa, Spain
| | - Isabel Andia
- Regenerative Therapies, Bioprinting Laboratory, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; (C.D.A.); (A.P.-V.); (I.J.)
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11
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Salhi N, Bouyahya A, Bounihi A, Masrar A, Bouabdellah M, Chabraoui L, Zengin G, Taghzouti K, Rouas L, Cherrah Y. Investigation of wound healing activity Cynara humilis of root extracts. J Cosmet Dermatol 2021; 21:1596-1609. [PMID: 34008875 DOI: 10.1111/jocd.14237] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/29/2021] [Accepted: 05/12/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Wound healing is among the frequent illnesses that affects the skin, and therefore, the screening of natural preparation to treat skin burn is important. In Morocco, Cynara humilis is a Moroccan medicinal plant widely used for the treatment of skin burn. OBJECTIVES The aim of this study was to investigate the safety of C. humilis and its wound healing potential against skin burn. METHODS In this work, C. humilis was selected based on an ethnopharmacological survey. As revealed by traditional medicine, C. humilis powder extract (CHPE) was used to test wound healing effects. Furthermore, to assure the safety of this powder, acute and subchronic dermal toxicities were investigated on animal models. RESULTS The oral acute toxicity test of CHPE did not show mortality in treated rats (LD50 >2000 mg/kg). Moreover, in the acute dermal toxicity, CHPE at 5 g/kg did not induce clinical signs observed during the observation period of 48 h. In the subchronic toxicity test, CHPE did not cause significant abnormalities in the physiological parameters and pathological changes in the major organs of the rats. Body weight evolution and macroscopic analysis of skin burn showed CHPE exhibited important wound healing effects in a time-dependent manner. CHPE reduced significantly wound surface (6.93 ± 0.25 cm2 ) compared with the SDA group (8.30 ± 0.37 cm2 ) and the no-treated group (10.05 ± 0.28 cm2 ). Moreover, the retention rate was increased importantly after the treatment with CHPE (61.66 ± 1.42%) compared with the SDA-treated group (53.57% ± 2.83%) and the no-treated group control animals (43.34% ± 1.27%). CONCLUSION These results were confirmed by a histological evaluation, which showed that CHPE increased the neovascularization, the collagen deposition, and the re-epithelialization. The findings of this work suggest that CHPE could be a promising source for developing drugs against skin burn.
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Affiliation(s)
- Najoua Salhi
- Pharmacoepidemiology and Pharmacoeconomics Research Team, Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.,Pharmacodynamics Research Team ERP, Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Faculty of Sciences, Department of Biology, and Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
| | - Amina Bounihi
- Pharmacodynamics Research Team ERP, Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
| | - Azlarab Masrar
- Central laboratory of Hematology, Ibn Sina Hospital, Rabat, Morocco
| | | | - Layachi Chabraoui
- Central laboratory of Biochemistry, Ibn Sina Hospital, Rabat, Morocco
| | - Gokhan Zengin
- Physiology and Biochemistry Research Laboratory, Department of Biology, Science Faculty, Selcuk University, Konya, Turkey
| | - Khalid Taghzouti
- Team of Animal Physiology and Physiopathology, Department of Biology, Faculty of Sciences, and Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
| | - Lamiae Rouas
- Laboratory of Anatomy Cytology, Faculty of Medicine and Pharmacy, Children's Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Yahya Cherrah
- Pharmacoepidemiology and Pharmacoeconomics Research Team, Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
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12
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Won JE, Shin JH, Kim J, Kim WJ, Ryu JJ, Shim JS. Multi-functional effects of a nitric oxide-conjugated copolymer for accelerating palatal wound healing. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 125:112090. [PMID: 33965100 DOI: 10.1016/j.msec.2021.112090] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 03/22/2021] [Accepted: 03/26/2021] [Indexed: 12/27/2022]
Abstract
The damaged site of a palatal wound is difficult to repair and often remains unclosed due to failure of the healing process, which occurs in inadequate environments of the oral cavity. Nitric oxide (NO) has effective functions in repairing damaged tissues, but it has a limitation due to short lifetime and rapid diffusion. Here, we synthesize a donor to deliver exogenous NO gas and verify its therapeutic effect for the palatal wound healing, which is known to take longer for healing due to the poor environment of warm saliva containing millions of microbes. NO was incorporated into the synthetic polymer and the NO-donors were characterized based upon their ability to release NO. The NO donor not only reduced cytotoxicity but also increased migration and proliferation in gingival fibroblasts. Moreover, the angiogenic capacity was improved by NO-donor treatment. In the palatal wound model, the NO-treatment was involved in enhancing the biological responses associated with wound healing. This strategy suggests that treatment involving controlled NO release may have beneficial effects on palatal wound healing.
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Affiliation(s)
- Jong-Eun Won
- Department of Dentistry, Korea University Guro Hospital, Seoul, Republic of Korea; Institute of Clinical Dental Research, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Jung Hyun Shin
- Department of Dentistry, Dankook University Jukjeon Dental Hospital, Gyeonggi-do, Republic of Korea
| | - Jinseong Kim
- Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
| | - Won Jong Kim
- Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
| | - Jae Jun Ryu
- Department of Dentistry, Korea University Anam Hospital, Seoul, Republic of Korea
| | - Ji Suk Shim
- Department of Dentistry, Korea University Guro Hospital, Seoul, Republic of Korea; Institute of Clinical Dental Research, Korea University Guro Hospital, Seoul, Republic of Korea.
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13
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Li D, Ren JW, Xu T, Li L, Liu P, Li Y. Effect of bovine bone collagen oligopeptides on wound healing in mice. Aging (Albany NY) 2021; 13:9028-9042. [PMID: 33690172 PMCID: PMC8034929 DOI: 10.18632/aging.202750] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Accepted: 02/08/2021] [Indexed: 01/01/2023]
Abstract
Impaired wound healing often brings a set of problems in clinical practice. This study aimed to observe the wound healing potential of bovine bone collagen oligopeptides (BCOP) in mice. After an operation, mice in BCOP-treated groups were given intragastric administration of BCOP, while others were administered vehicle. Mice were sacrificed at different points. The wound healing condition and the tensile strength were observed, serum biochemical indexes and mRNA expression of level of related genes were measured. Compared with the normal control group, albumin (ALB), prealbumin (PA), transferrin (TRF), hydroxyproline (Hyp) levels and tension strength in the BCOP-treated groups increased significantly (p < 0.05). A pathological report showed that neutrophil granulocyte in the BCOP-treated groups decreased, while blood capillary and fibroblasts increased. The levels of serum inflammation indexes like interleukin (IL)-8, tumor necrosis factor (TNF)-α, chemokine (C-C motif) ligand 2 (CCL2) and C-reactive protein (CRP) significantly decreased in full-thickness incision model, whereas increased in full-thickness excision model (p < 0.05). Furthermore, IL-10, stromal cell-derived factor-1 alpha (SDF-1α) levels and the mRNA expression of vascular endothelial growth factor (VEGF) significantly increased in both models (p < 0.05). These results suggested that oral administration of BCOP could promote wound healing in mice.
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Affiliation(s)
- Di Li
- Department of Clinical Nutrition, Peking University People's Hospital, Beijing 100044, China
| | - Jin-Wei Ren
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China
| | - Teng Xu
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China
| | - Lin Li
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China
| | - Peng Liu
- Department of Clinical Nutrition, Peking University People's Hospital, Beijing 100044, China
| | - Yong Li
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China
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14
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Harn HIC, Chen CC, Wang SP, Lei M, Chuong CM. Tissue Mechanics in Haired Murine Skin: Potential Implications for Skin Aging. Front Cell Dev Biol 2021; 9:635340. [PMID: 33681217 PMCID: PMC7933214 DOI: 10.3389/fcell.2021.635340] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 02/01/2021] [Indexed: 12/19/2022] Open
Abstract
During aging, the skin undergoes changes in architecture and composition. Skin aging phenotypes occur due to accumulated changes in the genome/epigenome, cytokine/cell adhesion, cell distribution/extracellular matrix (ECM), etc. Here we review data suggesting that tissue mechanics also plays a role in skin aging. While mouse and human skin share some similarities, their skin architectures differ in some respects. However, we use recent research in haired murine skin because of the available experimental data. Skin suffers from changes in both its appendages and inter-appendage regions. The elderly exhibit wrinkles and loose dermis and are more likely to suffer from wounds and superficial abrasions with poor healing. They also have a reduction in the number of skin appendages. While telogen is prolonged in aging murine skin, hair follicle stem cells can be rejuvenated to enter anagen if transplanted to a young skin environment. We highlight recent single-cell analyses performed on epidermis and aging human skin which identified new basal cell subpopulations that shift in response to wounding. This may be due to alterations of basement membrane stiffness which would change tissue mechanics in aging skin, leading to altered homeostatic dynamics. We propose that the extracellular matrix (ECM) may play a key role as a chemo-mechanical integrator of the multi-layered senescence-associated signaling pathways, dictating the tissue mechanical landscape of niche microenvironments in aging phenotypes. We show examples where failed chemo-mechanical signaling leads to deteriorating homeostasis during skin aging and suggest potential therapeutic strategies to guide future research to delay the aging processes.
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Affiliation(s)
- Hans I-Chen Harn
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.,International Research Center of Wound Repair and Regeneration (iWRR), National Cheng Kung University, Tainan, Taiwan
| | - Chih-Chiang Chen
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Dermatology, National Yang-Ming University, Taipei, Taiwan
| | - Sheng-Pei Wang
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.,International Research Center of Wound Repair and Regeneration (iWRR), National Cheng Kung University, Tainan, Taiwan
| | - Mingxing Lei
- 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing, China.,Key Laboratory of Biorheological Science and Technology of the Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China
| | - Cheng-Ming Chuong
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
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15
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Ozdogan CY, Kenar H, Davun KE, Yucel D, Doger E, Alagoz S. An in vitro 3D diabetic human skin model from diabetic primary cells. Biomed Mater 2020; 16:015027. [PMID: 33331294 DOI: 10.1088/1748-605x/abc1b1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Diabetes mellitus, a complex metabolic disorder, leads to many health complications like kidney failure, diabetic heart disease, stroke, and foot ulcers. Treatment approaches of diabetes and identification of the mechanisms underlying diabetic complications of the skin have gained importance due to continued rapid increase in the diabetes incidence. A thick and pre-vascularized in vitro 3D type 2 diabetic human skin model (DHSM) was developed in this study. The methacrylated gelatin (GelMA) hydrogel was produced by photocrosslinking and its pore size (54.85 ± 8.58 μm), compressive modulus (4.53 ± 0.67 kPa) and swelling ratio (17.5 ± 2.2%) were found to be suitable for skin tissue engineering. 8% GelMA hydrogel effectively supported the viability, spreading and proliferation of human dermal fibroblasts. By isolating dermal fibroblasts, human umbilical vein endothelial cells and keratinocytes from type 2 diabetic patients, an in vitro 3D type 2 DHSM, 12 mm in width and 1.86 mm thick, was constructed. The skin model consisted of a continuous basal epidermal layer and a dermal layer with blood capillary-like structures, ideal for evaluating the effects of anti-diabetic drugs and wound healing materials and factors. The functionality of the DHSM was showed by applying a therapeutic hydrogel into its central wound; especially fibroblast migration to the wound site was evident in 9 d. We have demonstrated that DHSM is a biologically relevant model with sensitivity and predictability in evaluating the diabetic wound healing potential of a therapeutic material.
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Affiliation(s)
- Candan Yilmaz Ozdogan
- Experimental and Clinical Research Center, Diabetes and Obesity Research Laboratory, Kocaeli University, Kocaeli, Turkey. Department of Biology, Graduate School of Natural and Applied Sciences, Kocaeli University, Kocaeli, Turkey
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16
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Arif S, Larochelle S, Moulin VJ. PLGF-1 contained in normal wound myofibroblast-derived microvesicles stimulated collagen production by dermal fibroblasts. J Cell Commun Signal 2020; 14:427-438. [PMID: 32613356 DOI: 10.1007/s12079-020-00572-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 06/23/2020] [Indexed: 12/24/2022] Open
Abstract
During the last stages of wound healing, myofibroblasts differentiate mainly from fibroblasts. Myofibroblasts from normal skin wounds (Wmyo) can communicate with its surrounding using secreted factors. They also have the capacity to produce microvesicles (MVs), a type of extracellular vesicles, as mediators of intercellular communication. MVs cargo are potentially capable of regulating the behavior of targeted cells and tissues. The aim of this study is to evaluate the effect of Wmyo-derived MVs on dermal fibroblasts and to determine the responsible signaling molecule. Microvesicles were obtained from culture media of myofibroblasts and characterized using protein quantification, dynamic light scattering and transmission electron microscopy. Uptake of fluorescent MVs in fibroblasts was assessed by flow cytometry. Cytokines concentrations were quantified in MV samples by a multiplex ELISA. Different concentration of MVs or a selected cytokine were used as treatments over fibroblasts culture for 5 days. Following the treatments, parameters linked to the extracellular matrix were studied. Lastly, the selected cytokine was neutralized within MVs before evaluating collagen production. We showed that Wmyo derived-MVs were internalized by dermal fibroblasts. Cytokine array analysis revealed that a large amount of placental growth factor 1 (PLGF-1) (0.88 ± 0.63 pg/μg proteins in MVs) could be detected in MVs samples. Cutaneous fibroblasts treated with MVs or PLGF-1 showed significantly stimulated procollagen I level production (Fold change of 1.80 ± 0.18 and 2.07 ± 0.18, respectively). Finally, the neutralization of PLGF-1 in MVs significantly inhibited the production of procollagen I by fibroblasts. Our study shows that Wmyo derived-MVs are involved in intercellular communication by stimulating collagen production by fibroblasts during wound healing. This effect is possibly attained through PLGF-1 signalling. These findings represent a promising opportunity to gain insight into how MVs and Wmyo may mediate the healing of a skin wound.
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Affiliation(s)
- Syrine Arif
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada
| | - Sébastien Larochelle
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada
| | - Véronique J Moulin
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada.
- Department of Surgery, Faculty of Medicine, Université Laval, Quebec, QC, Canada.
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17
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H. Moglad E, Fatima F, Muqtader A M, Devanathad V, Khalid Anw M, F. Aldawsa M. Development of Topical Antibacterial Gel Loaded with Cefadroxil Solid Lipid Nanoparticles: In vivo Wound Healing Activity and Epithelialization Study. INT J PHARMACOL 2020. [DOI: 10.3923/ijp.2020.298.309] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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18
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Zafari M, Mansouri M, Omidghaemi S, Yazdani A, Pourmotabed S, Hasanpour Dehkordi A, Nosrati H, Validi M, Sharifi E. Physical and biological properties of blend-electrospun polycaprolactone/chitosan-based wound dressings loaded with N-decyl-N, N-dimethyl-1-decanaminium chloride: An in vitro and in vivo study. J Biomed Mater Res B Appl Biomater 2020; 108:3084-3098. [PMID: 32459395 DOI: 10.1002/jbm.b.34636] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 03/16/2020] [Accepted: 04/29/2020] [Indexed: 01/05/2023]
Abstract
Dual-pump electrospinning of antibacterial N-decyl-N, N-dimethyl-1-decanaminium-chloride (DDAC)-loaded polycaprolactone (PCL) nanofibers, and chitosan (CS)/polyethylene-oxide (PEO)-based wound dressings with hydrophilic and hydrophobic properties to eliminate and absorb pathogenic bacteria from wound surface besides antibacterial action and to support wound healing and accelerate its process. Physicochemical properties of the prepared nanofibrous mat as well as antibacterial, cytotoxicity, and cell compatibility were studied. The full-thickness excisional wound healing properties up to 3 weeks using hematoxylin and eosin and Masson-trichrome staining were investigated. Addition of DDAC to CS/PEO-PCL mats decreased the diameter of the nanofibers, which is a crucial property for wound healing as large surface area per volume ratio of nanofibers, in addition to proper cell adhesion, increases loading of DDAC in mats and leads to increased cell viability and eliminating Gram-positive bacteria at in vitro studies. In vivo studies showed DDAC-loaded CS/PEO-PCL mats increased epithelialization and angiogenesis and decreased the inflammation according to histological results. We demonstrated that hydrophobic PCL/DDAC mats, besides antibacterial properties of DDAC, absorbed and eliminated the hydrophobic pathological microorganisms, whereas the hydrophilic nanofibers consisted of CS/PEO, increased the cell adhesion and proliferation due to positive charge of CS. Finally, we were able to increase the wound healing quality by using multifunctional wound dressing. CS/PEO-PCL containing 8 wt % of DDAC nanofibrous mats is promising as a wound dressing for wound management due to the favorable interactions between the pathogenic bacteria and PCL/CS-based wound dressing.
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Affiliation(s)
- Mahdi Zafari
- Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran.,Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Milad Mansouri
- Cellular and Molecular Research Center, Basic Health Science Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Shadi Omidghaemi
- Cellular and Molecular Research Center, Basic Health Science Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Amid Yazdani
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Samiramis Pourmotabed
- Department of Emergency Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ali Hasanpour Dehkordi
- Social Determinants of Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Hamed Nosrati
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Majid Validi
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Esmaeel Sharifi
- Department of Tissue Engineering and Biomaterials, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran
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19
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Cheng N, Jeschke MG, Sheikholeslam M, Datu AK, Oh HH, Amini-Nik S. Promotion of dermal regeneration using pullulan/gelatin porous skin substitute. J Tissue Eng Regen Med 2019; 13:1965-1977. [PMID: 31350941 PMCID: PMC7020691 DOI: 10.1002/term.2946] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 07/11/2019] [Accepted: 07/15/2019] [Indexed: 12/18/2022]
Abstract
Tissue-engineered dermal substitutes represent a promising approach to improve wound healing and provide more sufficient regeneration, compared with current clinical standards on care of large wounds, early excision, and grafting of autografts. However, inadequate regenerative capacity, impaired regeneration/degradation profile, and high cost of current commercial tissue-engineered dermal regeneration templates hinder their utilization, and the development of an efficient and cost-effective tissue-engineered dermal substitute remains a challenge. Inspired from our previously reported data on a pullulan/gelatin scaffold, here we present a new generation of a porous pullulan/gelatin scaffold (PG2) served as a dermal substitute with enhanced chemical and structural characteristics. PG2 shows excellent biocompatibility (viability, migration, and proliferation), assessed by in vitro incorporation of human dermal fibroblasts in comparison with the Integra® dermal regeneration template (Control). When applied on a mouse full-thickness excisional wound, PG2 shows rapid scaffold degradation, more granulation tissue, more collagen deposition, and more cellularity in comparison with Control at 20 days post surgery. The faster degradation is likely due to the enhanced recruitment of inflammatory macrophages to the scaffold from the wound bed, and that leads to earlier maturation of granulation tissue with less myofibroblastic cells. Collectively, our data reveal PG2's characteristics as an applicable dermal substitute with excellent dermal regeneration, which may attenuate scar formation.
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Affiliation(s)
- Nan Cheng
- Sunnybrook Research Institute, University of Toronto, Toronto, ON M4N 3M5, Canada
| | - Marc G Jeschke
- Sunnybrook Research Institute, University of Toronto, Toronto, ON M4N 3M5, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada
- Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada
- Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada
- Ross-Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
| | | | - Andrea-Kaye Datu
- Sunnybrook Research Institute, University of Toronto, Toronto, ON M4N 3M5, Canada
| | - Hwan Hee Oh
- Sunnybrook Research Institute, University of Toronto, Toronto, ON M4N 3M5, Canada
| | - Saeid Amini-Nik
- Sunnybrook Research Institute, University of Toronto, Toronto, ON M4N 3M5, Canada
- Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
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20
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Effect of Keratinocytes on Myofibroblasts in Hypertrophic Scars. Aesthetic Plast Surg 2019; 43:1371-1380. [PMID: 31346713 DOI: 10.1007/s00266-019-01434-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Accepted: 06/18/2019] [Indexed: 01/03/2023]
Abstract
Myofibroblasts play a central role in matrix formation and wound contraction during wound healing and undergo apoptosis at the end of the healing. Hypertrophic scarring is a pathologic condition in which myofibroblasts persist in the tissue. It has been hypothesized that abnormalities in epidermal-dermal crosstalk underlie this pathology. Therefore, in this study, we investigated whether myofibroblasts are affected by keratinocytes. Transforming growth factor beta-induced myofibroblasts (Imyo) and myofibroblasts from hypertrophic scar tissue (Hmyo) were characterized using microarrays. Keratinocytes were co-cultured with myofibroblasts, and quantitative PCR analysis was performed. We found that numerous extracellular matrix- and smooth muscle cell-associated genes were upregulated in Imyo and Hmyo respectively, and these findings suggest that Hmyo are fully differentiated myofibroblasts and that Imyo are less differentiated than Hmyo. Decreased collagen type 1 gene expression was found in keratinocytes co-cultured with Imyo and Hmyo; further, α-smooth muscle actin expression in Imyo increased in the presence of keratinocytes. These observations indicate that keratinocytes play a role in the development of pathological fibrosis in hypertrophic scar tissue by regulating the behavior of dermal fibroblasts and myofibroblasts. We believe that this study provides the basis for understanding the pathophysiology of hypertrophic scarring and identifying new therapeutic approaches for this dysfunction.No Level Assigned This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors - www.springer.com/00266 .
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Shao Y, Dang M, Lin Y, Xue F. Evaluation of wound healing activity of plumbagin in diabetic rats. Life Sci 2019; 231:116422. [DOI: 10.1016/j.lfs.2019.04.048] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 04/08/2019] [Accepted: 04/18/2019] [Indexed: 12/13/2022]
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Jee JP, Pangeni R, Jha SK, Byun Y, Park JW. Preparation and in vivo evaluation of a topical hydrogel system incorporating highly skin-permeable growth factors, quercetin, and oxygen carriers for enhanced diabetic wound-healing therapy. Int J Nanomedicine 2019; 14:5449-5475. [PMID: 31409998 PMCID: PMC6647010 DOI: 10.2147/ijn.s213883] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 06/27/2019] [Indexed: 12/19/2022] Open
Abstract
PURPOSE We created and evaluated an enhanced topical delivery system featuring a combination of highly skin-permeable growth factors (GFs), quercetin (QCN), and oxygen; these synergistically accelerated re-epithelialization and granulation tissue formation of/in diabetic wounds by increasing the levels of GFs and antioxidants, and the oxygen partial pressure, at the wound site. METHODS To enhance the therapeutic effects of exogenous administration of GFs for the treatment of diabetic wounds, we prepared highly skin-permeable GF complexes comprised of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), platelet-derived growth factor-A (PDGF-A), and basic fibroblast growth factor (bFGF), genetically attached, via the N-termini, to a low-molecular-weight protamine (LMWP) to form LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and LMWP-bFGF, respectively. Furthermore, quercetin (QCN)- and oxygen-carrying 1-bromoperfluorooctane (PFOB)-loaded nanoemulsions (QCN-NE and OXY-PFOB-NE) were developed to improve the topical delivery of QCN and oxygen, respectively. After confirming the enhanced penetration of LMWP-GFs, QCN-NE, and oxygen delivered from OXY-PFOB-NE across human epidermis, we evaluated the effects of combining LMWP-GFs, QCN-NE, and OXY-PFOB-NE on proliferation of keratinocytes and fibroblasts, and the chronic wound closure rate of a diabetic mouse model. RESULTS The optimal ratios of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, LMWP-bFGF, QCN-NE, and OXY-PFOB-NE were 1, 1, 0.02, 0.02, 0.2, and 60, respectively. Moreover, a Carbopol hydrogel containing LMWP-GFs, QCN-NE, and OXY-PFOB-NE (LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL) significantly improved scratch-wound recovery of keratinocytes and fibroblasts in vitro compared to that afforded by hydrogels containing each component alone. LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL significantly accelerated wound-healing in a diabetic mouse model, decreasing wound size by 54 and 35% compared to the vehicle and LMWP-GFs, respectively. CONCLUSION LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL synergistically accelerated the healing of chronic wounds, exerting both rapid and prolonged effects.
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Affiliation(s)
- Jun-Pil Jee
- College of Pharmacy, Chosun University, Gwangju61452, Republic of Korea
| | - Rudra Pangeni
- College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam58554, Republic of Korea
| | - Saurav Kumar Jha
- College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam58554, Republic of Korea
| | - Youngro Byun
- Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, College of Pharmacy, Seoul National University, Seoul08826, Republic of Korea
| | - Jin Woo Park
- College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam58554, Republic of Korea
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Evaluation of the Biological Effects of Lyophilized Hydrophilic Extract of Rhus coriaria on Myeloperoxidase (MPO) Activity, Wound Healing, and Microbial Infections of Skin Wound Tissues. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:5861537. [PMID: 31379964 PMCID: PMC6662417 DOI: 10.1155/2019/5861537] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2018] [Revised: 06/03/2019] [Accepted: 07/02/2019] [Indexed: 01/11/2023]
Abstract
Impaired wound healing was mainly associated with severe microbial infections which significantly affect diagnostic and therapeutic strategies. Thus, in this study, the potential wound healing activity, anti-inflammatory, and antimicrobial activity of an aqueous extract of Rhus coriaria extract (AERc) were evaluated by wound contraction, scar formation, period of epithelization, MPO enzyme activity, collagenase-2 (MMP-8), hydroxyproline (HPX), and collagen deposition as markers of wound healing at different days of postwound. Phytoconstituents, microbial activity, and fibrogenic markers were screened by HPLC, disc-diffusion, and colorimetric assays. The animals were treated with Rhus coriaria extract (AERc) concentrations at doses of 5 mg.kg−1and 10 mg.kg−1, respectively. On days 6 and 9, the AERc-treated animals at doses of 5 mg.mL−1 and 10 mg.mL−1 exhibited a significant reduction in the wound area, increased deposition of collagen, HPX, and reduction in MMP-8, and MPO enzyme activity when compared with controls. Scar formation and epithelization were completed in 10 days compared to controls. In addition, in wounds infected separately with Staph. aureus or P. aeruginosa, the AERc extract significantly improved wound contraction, deposition of collagen, and HPx and reduced MMP-8 and MPO concentrations, with complete epithelization of wounds in 10-13 days compared to the saline-treated group. Hydrolyzable tannins, gallic acid, quercetin, and myricetin were the most common active components of AERc. In vitro, the AERc and its components were effective against a set of microbes especially Staph. aureus, P. aeruginosa, and Staph. aureus (MRSA). In conclusion, the results showed that antimicrobial, anti-inflammatory, and antioxidant activity of Rhus coriaria extract suggested its importance as a target for formulation of novel drugs against many microbial infections with minimal side effects and could play a good potential role in accelerating wound healing activity via promoting myofibroblast activity, increase of hydroxyproline and collagen deposition, and regulation of MMP-8 and MPO enzyme activities.
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Beserra FP, Vieira AJ, Gushiken LFS, de Souza EO, Hussni MF, Hussni CA, Nóbrega RH, Martinez ERM, Jackson CJ, de Azevedo Maia GL, Rozza AL, Pellizzon CH. Lupeol, a Dietary Triterpene, Enhances Wound Healing in Streptozotocin-Induced Hyperglycemic Rats with Modulatory Effects on Inflammation, Oxidative Stress, and Angiogenesis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:3182627. [PMID: 31210838 PMCID: PMC6532325 DOI: 10.1155/2019/3182627] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 03/29/2019] [Accepted: 04/08/2019] [Indexed: 12/21/2022]
Abstract
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.
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Affiliation(s)
- Fernando Pereira Beserra
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Ana Júlia Vieira
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | | | - Eduardo Oliveira de Souza
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Maria Fernanda Hussni
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Carlos Alberto Hussni
- Department of Surgery and Veterinary Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Rafael Henrique Nóbrega
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | | | - Christopher John Jackson
- Kolling Institute of Medical Research, The University of Sydney at Royal North Shore Hospital, Sydney, Australia
| | | | - Ariane Leite Rozza
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Cláudia Helena Pellizzon
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
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25
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Patel M, Nakaji‐Hirabayashi T, Matsumura K. Effect of dual‐drug‐releasing micelle–hydrogel composite on wound healingin vivoin full‐thickness excision wound rat model. J Biomed Mater Res A 2019; 107:1094-1106. [DOI: 10.1002/jbm.a.36639] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 01/24/2019] [Indexed: 01/01/2023]
Affiliation(s)
- Monika Patel
- School of Materials ScienceJapan Advanced Institute of Science and Technology Nomi, Ishikawa, 923‐1292 Japan
| | - Tadashi Nakaji‐Hirabayashi
- Graduate School of Science and EngineeringUniversity of Toyama Toyama, 930‐8555 Japan
- Graduate School of Innovative Life ScienceUniversity of Toyama Toyama, 930‐8555 Japan
| | - Kazuaki Matsumura
- School of Materials ScienceJapan Advanced Institute of Science and Technology Nomi, Ishikawa, 923‐1292 Japan
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26
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27
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Antioxidant and anti-inflammatory properties of Prosopis cineraria based phenolic rich ointment in wound healing. Biomed Pharmacother 2018; 108:1572-1583. [DOI: 10.1016/j.biopha.2018.09.180] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 09/15/2018] [Accepted: 09/30/2018] [Indexed: 11/18/2022] Open
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28
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Parmar KM, Shende PR, Katare N, Dhobi M, Prasad SK. Wound healing potential of Solanum xanthocarpum in streptozotocin-induced diabetic rats. ACTA ACUST UNITED AC 2018; 70:1389-1400. [PMID: 29984407 DOI: 10.1111/jphp.12975] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 06/15/2018] [Indexed: 11/28/2022]
Abstract
OBJECTIVES The objective of the present study was to evaluate wound healing potential of Solanum xanthocarpum extract in streptozotocin-induced diabetic rats. METHODS Alcoholic extract of the aerial parts (ESX) was subjected to phytochemical estimations and its standardization with chlorogenic acid using HPLC. ESX was then evaluated for wound healing potential in, streptozotocin-induced diabetic rats using excision and incision wound models on topical and oral treatment Various biochemical evaluations, such as collagen, hexosamine, hyaluronic acid, protein, DNA along with antioxidant parameters, proinflammatory cytokines, VEGF and histopathological examination were also evaluated. KEY FINDINGS Extract of S. xanthocarpum depicted the presence of mainly alkaloids, polyphenols, steroids, while content of chlorogenic acid was found to be 8.44% w/w. The maximum effective nature of ESX in healing was observed at 10% gel (topical) and 200 mg/kg (orally) in diabetic rats, where highest healing power was observed when treated both orally and topically. Biochemical evaluations showed significant increase in the levels of collagen, hexosamine, hyaluronic acid, protein, DNA followed by significant decline in the levels of blood glucose, lipid peroxidation, nitric oxide and expression of proinflammatory cytokines, supported by histopathology. CONCLUSIONS The potential healing effect in diabetic rats may be attributed to the presence of chlorogenic acid in combination with other phytoconstituents.
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Affiliation(s)
- Komal M Parmar
- Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, India
| | - Priyanka R Shende
- Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, India
| | - Nitin Katare
- Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, India
| | - Mahaveer Dhobi
- Department of Pharmacognosy and Phytochemistry, Delhi Pharmaceutical Sciences and Research University, New Delhi, India
| | - Satyendra K Prasad
- Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, India
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29
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Doeser MC, Schöler HR, Wu G. Reduction of Fibrosis and Scar Formation by Partial Reprogramming In Vivo. Stem Cells 2018; 36:1216-1225. [PMID: 29761584 DOI: 10.1002/stem.2842] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Revised: 04/08/2018] [Accepted: 04/13/2018] [Indexed: 01/02/2023]
Abstract
Transient expression of the transcription factors OCT4, SOX2, KLF4, and C-MYC (OSKM) to induce partial reprogramming while avoiding the pluripotent state and teratoma formation has recently been discussed as a strategy for regenerating damaged tissues in vivo, whereby the impact of partial reprogramming on tissue repair remains to be elucidated. Here, we activated OSKM transcription factors in cutaneous wounds of OSKM-inducible transgenic mice and found that induction of OSKM factors in excisional wounds caused a diminished fibroblast transdifferentiation to myofibroblasts and wound contraction. Gene expression analyses showed downregulation of the profibrotic marker genes transforming growth factor beta 1, Collagen I, and vascular endothelial growth factor. Consequently, histological analyses demonstrated that OSKM induction in incisional wounds resulted in reduced scar tissue formation. These data provide proof of concept that OSKM-mediated partial reprogramming in situ can diminish fibrosis and improve tissue healing with less scar formation without the risk of tumor formation. This new insight into the effects of partial reprogramming in vivo may be relevant for developing reprogramming-based regenerative therapies for tissue injury and fibrotic diseases. Stem Cells 2018;36:1216-1225.
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Affiliation(s)
- Markus C Doeser
- Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.,Medical Faculty, University of Münster, Münster, Germany
| | - Hans R Schöler
- Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.,Medical Faculty, University of Münster, Münster, Germany
| | - Guangming Wu
- Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany
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Wang L, He T, Fu A, Mao Z, Yi L, Tang S, Yang J. Hesperidin enhances angiogenesis via modulating expression of growth and inflammatory factor in diabetic foot ulcer in rats. EUR J INFLAMM 2018. [DOI: 10.1177/2058739218775255] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
One of the most devastating consequences of diabetes mellitus is a chronic condition, diabetic foot ulcer. Numerous investigations are being targeted to explore newer compounds for treatment of diabetic foot ulcer wounds in diabetic patients. Hesperidin (HSP), an isoflavone glycoside has been established to exhibit antidiabetic and antioxidant potential. In the current investigation, diabetes was induced in rats by administration by streptozotocin (STZ) intraperitoneally (50 mg/kg). Wound-healing capacity was estimated in hind paw of rats by artificially initiating wound injury on the paw dorsal surface. The injured animals were administered with incremental doses of HSP suspension orally (10, 20, 40, 60, and 80 mg/kg) and insulin subcutaneously (10 IU/kg). Parameters such as wound area were estimated every 2 days, and at the end of 20 days of study, biochemical estimations in serum and histopathological observations of the wound were made. HSP (60 and 80 mg/kg) revealed statistically significant ( P < 0.05) improvement in wound dimension, glucose and insulin concentration, and glycated hemoglobin (HbA1C). Administration of HSP indicated significant ( P < 0.05) modulation of mRNA associated with expression of vascular endothelial growth factor (VEGF), whereas the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were lowered compared to the control group of animals. Real-time quantitative polymerase chain reaction (RT-qPCR) indicated expression of vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2) compared to glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Histological observations indicated higher expression of VEGF in the groups receiving HSP, indicative of angiogenesis stimulation in the diabetic wound. The results advocate angiogenesis activity of HSP was enhanced owing to reduction in hyperglycemia and oxidative stress–induced damage, reduced expression of inflammatory mediators, and enhanced expression of growth-related factors, thereby promoting healing of diabetic foot ulcer.
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Affiliation(s)
- Li Wang
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ting He
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Adan Fu
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhijin Mao
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lan Yi
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Sha Tang
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Yang
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Li W, Kandhare AD, Mukherjee AA, Bodhankar SL. Hesperidin, a plant flavonoid accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats: Role of TGF-ß/Smads and Ang-1/Tie-2 signaling pathways. EXCLI JOURNAL 2018; 17:399-419. [PMID: 29805347 PMCID: PMC5962903 DOI: 10.17179/excli2018-1036] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Accepted: 03/28/2018] [Indexed: 12/14/2022]
Abstract
Background: Delayed wound healing is a diverse, multifactorial, complex and inter-related complication of diabetes resulting in significant clinical morbidity. Hesperidin possesses potent antidiabetic and wound healing activity. Aim: To evaluate the potential of hesperidin against experimentally induced diabetes foot ulcers. Methods: Diabetes was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.) in Sprague Dawley rats (180-220 g) and wounds were created on the dorsal surface of the hind paw of rats. Hesperidin (25, 50 and 100 mg/kg, p.o.) was administered for 21 days after wound stabilization. Various biochemical, molecular and histopathological parameters were evaluated in wound tissue. Results: STZ-induced decrease in body weight and increase in blood glucose, food, and water intake was significantly (p < 0.05) inhibited by hesperidin (50 and 100 mg/kg) treatment. It showed a significant increase (p < 0.05) in percent wound closure and serum insulin level. The STZ-induced decrease in SOD and GSH level, as well as elevated MDA and NO levels, were significantly (p < 0.05) attenuated by hesperidin (50 and 100 mg/kg) treatment. Intraperitoneal administration of STZ caused significant down-regulation in VEGF-c, Ang-1, Tie-2, TGF-β and Smad 2/3 mRNA expression in wound tissues whereas hesperidin (50 and 100 mg/kg) treatment showed significant up-regulation in these mRNA expressions. STZ-induced alteration in would architecture was also attenuated by hesperidin (50 and 100 mg/kg) treatment. Conclusion: Together, treatment with hesperidin accelerate angiogenesis and vasculogenesis via up-regulation of VEGF-c, Ang-1/Tie-2, TGF-β and Smad-2/3 mRNA expression to enhance wound healing in chronic diabetic foot ulcers.
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Affiliation(s)
- Wenbin Li
- Department of Dermatology, Shaanxi Traditional Chinese Medicine Hospital, Xi'an, Shaanxi, 710003, China
| | - Amit D Kandhare
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Paud Road, Pune-411 038, India.,Jalan Universiti Bandar Barat, 31900, Kampar, Perak, Malaysia
| | - Anwesha A Mukherjee
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Paud Road, Pune-411 038, India
| | - Subhash L Bodhankar
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Paud Road, Pune-411 038, India
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32
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Sadiq A, Shah A, Jeschke MG, Belo C, Qasim Hayat M, Murad S, Amini-Nik S. The Role of Serotonin during Skin Healing in Post-Thermal Injury. Int J Mol Sci 2018; 19:ijms19041034. [PMID: 29596386 PMCID: PMC5979562 DOI: 10.3390/ijms19041034] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 03/24/2018] [Accepted: 03/26/2018] [Indexed: 12/24/2022] Open
Abstract
Post-burn trauma significantly raises tissue serotonin concentration at the initial stages of injury, which leads us to investigate its possible role in post burn wound healing. Therefore, we planned this study to examine the role of serotonin in wound healing through in vitro and in vivo models of burn injuries. Results from in vitro analysis revealed that serotonin decreased apoptosis and increased cell survival significantly in human fibroblasts and neonatal keratinocytes. Cellular proliferation also increased significantly in both cell types. Moreover, serotonin stimulation significantly accelerated the cell migration, resulting in narrowing of the scratch zone in human neonatal keratinocytes and fibroblasts cultures. Whereas, fluoxetine (a selective serotonin reuptake inhibitor) and ketanserin (serotonin receptor 2A inhibitor) reversed these effects. Scald burn mice model (20% total body surface area) showed that endogenous serotonin improved wound healing process in control group, whereas fluoxetine and ketanserin treatments (disruptors of endogenous serotonin stimulation), resulted in poor reepithelization, bigger wound size and high alpha smooth muscle actin (α-SMA) count. All of these signs refer a prolonged differentiation state, which ultimately exhibits poor wound healing outcomes. Collectively, data showed that the endogenous serotonin pathway contributes to regulating the skin wound healing process. Hence, the results of this study signify the importance of serotonin as a potential therapeutic candidate for enhancing skin healing in burn patients.
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Affiliation(s)
- Alia Sadiq
- Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
- Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences & Technology (NUST), H-12 Islamabad, Pakistan.
| | - Ahmed Shah
- Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
| | - Marc G Jeschke
- Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
- Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada.
| | - Cassandra Belo
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
| | - Muhammad Qasim Hayat
- Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences & Technology (NUST), H-12 Islamabad, Pakistan.
| | - Sheeba Murad
- Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences & Technology (NUST), H-12 Islamabad, Pakistan.
- Molecular Immunology Unit, The Institute of Infection and Immunity, St. George's, University of London, London SW17 0RE, UK.
| | - Saeid Amini-Nik
- Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
- Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada.
- Department of Laboratory Medicine and Pathobiology (LMP), University of Toronto, Toronto, ON M5S 1A8, Canada.
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Kurt B, Bilge N, Sözmen M, Aydın U, Önyay T, Özaydın I. Effects of Plantago lanceolata L. extract on full-thickness excisional wound healing in a mouse model. Biotech Histochem 2018; 93:249-257. [PMID: 29575942 DOI: 10.1080/10520295.2017.1421773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Wound healing requires cells that increase both collagen production as a result of inflammatory events and regeneration of epithelial tissue. The Plantago species of herbs have been used in traditional treatment of skin disorders and infectious diseases, and digestive, respiratory, reproductive and circulatory conditions. We investigated the efficacy of different concentrations of Plantago lanceolata L. extract (PLE) for wound healing owing to its anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant, anti-ulcerative, analgesic and immunomodulatory properties. We used 72 mice in four groups of 18. An excisional 1 cm wound was created in the skin on the back of the mice in all groups. An ointment containing 10% PLE was applied to the wound in group 1, an ointment containing 20% PLE was applied in group 2 and vaseline was applied in group 3. In group 4, no treatment was applied to the wound. On days 7, 14, and 21 of the experiment, six animals in each group were sacrificed after the wounds were photographed and specimens from the wound sites were examined. On day 14, epithelialization was more prominent in group 2, while vascularization and collagen deposition was more advanced in groups 1 and 2 compared to the other groups. Immunohistochemical examination revealed that TGF-β1 expression was elevated on day 14 in all groups; however, this elevation was more limited in groups 1 and 2 than in groups 3 and 4. Although ANGPT-2 expression increased in groups 1 and 4 on day 14, it decreased significantly in groups 2 and 3. We found that different concentrations of PLE exhibited positive effects on wound healing. Application of 10% PLE ointment may be a useful strategy for wound healing.
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Affiliation(s)
- B Kurt
- a Department of Surgery, Faculty of Veterinary Medicine , Kafkas University , Kars , Turkey
| | - N Bilge
- b Department of Food Safety and Public Health, Faculty of Veterinary Medicine , Kafkas University , Kars , Turkey
| | - M Sözmen
- c Department of Pathology, Faculty of Veterinary Medicine , Ondokuz Mayıs University , Samsun , Turkey
| | - U Aydın
- a Department of Surgery, Faculty of Veterinary Medicine , Kafkas University , Kars , Turkey
| | - T Önyay
- d Department of Surgery, Faculty of Veterinary Medicine , Ondokuz Mayıs University , Samsun , Turkey
| | - I Özaydın
- a Department of Surgery, Faculty of Veterinary Medicine , Kafkas University , Kars , Turkey
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Fan X, Zhu L, Wang K, Wang B, Wu Y, Xie W, Huang C, Chan BP, Du Y. Stiffness-Controlled Thermoresponsive Hydrogels for Cell Harvesting with Sustained Mechanical Memory. Adv Healthc Mater 2017; 6. [PMID: 28105774 DOI: 10.1002/adhm.201601152] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 11/23/2016] [Indexed: 01/17/2023]
Abstract
Most mechanobiological investigations focused on in situ mechanical regulation of cells on stiffness-controlled substrates with few downstream applications, as it is still challenging to harvest and expand mechanically primed cells by enzymatic digestion (e.g., trypsin) without interrupting cellular mechanical memory between passages. This study develops thermoresponsive hydrogels with controllable stiffness to generate mechanically primed cells with intact mechanical memory for augmented wound healing. No significant cellular property alteration of the fibroblasts primed on thermoresponsive hydrogels with varied stiffness has been observed through thermoresponsive harvesting. When reseeding the harvested cells for further evaluation, softer hydrogels are proven to better sustain the mechanical priming effects compared to rigid tissue culture plate, which indicates that both the stiffness-controlled substrate and thermoresponsive harvesting are required to sustain cellular mechanical memory between passages. Moreover, epigenetics analysis reveals that thermoresponsive harvesting could reduce the rearrangement and loss of chromatin proteins compared to that of trypsinization. In vivo wound healing using mechanically primed fibroblasts shows featured epithelium and sebaceous glands, which indicates augmented skin recovery compared with trypsinized fibroblasts. Thus, the thermoresponsive hydrogel-based cell harvesting system offers a powerful tool to investigate mechanobiology between cell passages and produces abundant cells with tailored mechanical priming properties for cell-based applications.
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Affiliation(s)
- Xingliang Fan
- Department of Biomedical Engineering; School of Medicine; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; Tsinghua University; Beijing 100084 China
- Joint Center for Life Sciences; Tsinghua University-Peking University; Beijing 100084 China
| | - Lu Zhu
- Department of Biomedical Engineering; School of Medicine; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; Tsinghua University; Beijing 100084 China
- Institute of Medical Equipment; Academy of Military Medical Sciences; Tianjin 300161 China
| | - Ke Wang
- Department of Chemistry; School of Science; Tsinghua University; Beijing 100084 China
| | - Bingjie Wang
- Department of Biomedical Engineering; School of Medicine; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; Tsinghua University; Beijing 100084 China
- School of Life Science; Tsinghua University; Beijing 100084 China
| | - Yaozu Wu
- Department of Biomedical Engineering; School of Medicine; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; Tsinghua University; Beijing 100084 China
| | - Wei Xie
- Joint Center for Life Sciences; Tsinghua University-Peking University; Beijing 100084 China
- School of Life Science; Tsinghua University; Beijing 100084 China
| | - Chengyu Huang
- Department of Plastic; Reconstructive and Aesthetic Surgery; Beijing Tsinghua Changgung Hospital; Tsinghua University; Beijing 102218 China
| | - Barbara Pui Chan
- Tissue Engineering Laboratory; Department of Mechanical Engineering; The University of Hong Kong; Pokfulam Road Hong Kong Special Administrative Region China
| | - Yanan Du
- Department of Biomedical Engineering; School of Medicine; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; Tsinghua University; Beijing 100084 China
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A Conditioned Medium of Umbilical Cord Mesenchymal Stem Cells Overexpressing Wnt7a Promotes Wound Repair and Regeneration of Hair Follicles in Mice. Stem Cells Int 2017; 2017:3738071. [PMID: 28337222 PMCID: PMC5350397 DOI: 10.1155/2017/3738071] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 09/25/2016] [Accepted: 10/05/2016] [Indexed: 01/19/2023] Open
Abstract
Mesenchymal stem cells (MSCs) can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM) from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs) overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM) components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM) can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair.
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van Beurden HE, Von den Hoff JW, Torensma R, Maltha JC, Kuijpers-Jagtman AM. Myofibroblasts in Palatal Wound Healing: Prospects for the Reduction of Wound Contraction after Cleft Palate Repair. J Dent Res 2016; 84:871-80. [PMID: 16183784 DOI: 10.1177/154405910508401002] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The surgical closure of orofacial clefts is considered to impair maxillary growth and dento-alveolar development. Wound contraction and subsequent scar tissue formation, during healing of these surgical wounds, contribute largely to these growth disturbances. The potential to minimize wound contraction and subsequent scarring by clinical interventions depends on the surgeon’s knowledge of the events responsible for these phenomena. Fibroblasts initiate wound contraction, but proto-myofibroblasts and mature myofibroblasts are by far the most important cells in this process. Myofibroblasts are characterized by their cytoskeleton, which contains alpha-smooth-muscle actin. Additionally, their contractile apparatus contains bundles of actin microfilaments and associated contractile proteins, such as non-muscle myosin. This contractile apparatus is thought to be the major force-generating element involved in wound contraction. After closure of the wound, the myofibroblasts disappear by apoptosis, and a less cellular scar is formed. A reduction of contraction and scarring might be obtained by inhibition of myofibroblast differentiation, stimulation of their de-differentiation, stimulation of myofibroblast apoptosis, or impairment of myofibroblast function. In this review, we will discuss all of these possibilities, which ultimately may lead to a better outcome of cleft palate surgery.
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Affiliation(s)
- H E van Beurden
- Department of Orthodontics and Oral Biology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
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Mckirdy SW, Chew B, Tzaffetta K, Naylor IL, Sharpe DT. Angiotensin receptors in Dupuytren's tissue: Implications for the pharnnacological treatment of Dupuytren's disease. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/175899830100600302] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The role of Angiotensin II as a pro-fibrotic mediator has been established in models of cardiac, hepatic and renal fibrosis. The administration of Angiotensin-Converting Enzyme (ACE) – inhibitors to these models results in a reduction in the myofibroblast population and collagen synthesis. In rodent excisionat wound-healing experiments, an ACE inhibitor reduced the rate of wound contraction, collagen deposition and angiogenesis. Using immunohistochemistry, the presence of Angiotensin I receptors was identified within tissue samples from patients with Dupuytren's disease. These were found to be co-localised with areas of myofibrobtast expression. This co-localisation has implications for the potential of pharmacological regulation of Dupuytren's disease. Further research is necessary to confirm whether the use of ACE-inhibitors can modulate this disease process, which until now has not been responsive to safe, effective pharmacological treatment.
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Affiliation(s)
| | - B.K. Chew
- University of Bradford, Bradford, UK
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Pinto BI, Tabor AJ, Stearns DM, Diller RB, Kellar RS. A Bench-Top In Vitro Wound Assay to Demonstrate the Effects of Platelet-Rich Plasma and Depleted Uranium on Dermal Fibroblast Migration. ACTA ACUST UNITED AC 2016; 2:151-156. [PMID: 28971114 DOI: 10.1089/aivt.2016.0001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Cellular migration assays are useful tools to investigate physiologic events on the bench top. Furthermore, this migration assay can be utilized to investigate wound healing therapeutics (those that encourage or accelerate wound closure) as well as deleterious agents (ones that mitigate or slow wound closure). The current study used an in vitro scratch assay to measure the effects of platelet-rich plasma (PRP) and depleted uranium (DU) in the form of uranyl acetate on cellular migration of human neonatal dermal fibroblasts in an in vitro simulation of wound healing. Data analyses included percent wound closure measured as the distance between cell margins, and rates of wound closure versus untreated controls. The highest doses of PRP (0.063, 0.125%) resulted in 50-65% wound closure after 4-8 hours relative to 38-44% in controls and the low-dose treatment group (0.031%). The high-dose treatments of PRP (0.125, 0.063%) reached 100% wound closure at 12 hours postwound versus 16 hours for controls and the low-dose treatment group (0.031%). Conversely, the higher doses of DU treatments (50 and 100 μM) resulted in <80% closure versus 100% closure in controls after 16 hours, with full closure observed at 20 hours. The highest dose of DU (1,000 μM) resulted in <20% closure versus 100% closure in controls after 16 hours. The use of the described scratch assay serves as a translatable bench-top model that has the potential to predict in vivo outcomes, and in many early studies can help to demonstrate proof-of-concept before moving into complex biological systems.
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Affiliation(s)
- Bronson I Pinto
- Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona
| | - Aaron J Tabor
- Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona
| | - Diane M Stearns
- Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, Arizona
| | - Robert B Diller
- Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona
| | - Robert S Kellar
- Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona.,Department of Mechanical Engineering, Northern Arizona University, Flagstaff, Arizona.,Center for Bioengineering Innovation, Northern Arizona University, Flagstaff, Arizona
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Paré B, Deschênes LT, Pouliot R, Dupré N, Gros-Louis F. An Optimized Approach to Recover Secreted Proteins from Fibroblast Conditioned-Media for Secretomic Analysis. Front Cell Neurosci 2016; 10:70. [PMID: 27064649 PMCID: PMC4814560 DOI: 10.3389/fncel.2016.00070] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Accepted: 03/04/2016] [Indexed: 11/13/2022] Open
Abstract
The proteins secreted by a particular type of cell, the secretome, play important roles in the regulation of many physiological processes via paracrine/autocrine mechanisms, and they are of increasing interest to help understanding rare diseases and to identify potential biomarkers and therapeutic targets. To facilitate ongoing research involving secreted proteins, we revisited cell culture protocols and whole secreted protein enrichment protocols. A reliable method for culturing and precipitating secreted protein from patient-derived fibroblast conditioned-medium was established. The method is based on the optimization of cell confluency and incubation time conditions. The well-established carrier-based TCA-DOC protein precipitation method was consistently found to give higher protein recovery yield. According to our results, we therefore propose that protein enrichment should be performed by TCA-DOC precipitation method after 48 h at 95% of confluence in a serum-deprived culture medium. Given the importance of secreted proteins as a source to elucidate the pathogenesis of rare diseases, especially neurological disorders, this approach may help to discover novel candidate biomarkers with potential clinical significance.
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Affiliation(s)
- Bastien Paré
- Division of Regenerative Medicine, Laval University Experimental Organogenesis Research Center/LOEX, CHU de Québec Research Center - Enfant-Jésus HospitalQuébec, QC, Canada; Department of Surgery, Faculty of Medicine, Laval UniversityQuébec, QC, Canada
| | - Lydia T Deschênes
- Division of Regenerative Medicine, Laval University Experimental Organogenesis Research Center/LOEX, CHU de Québec Research Center - Enfant-Jésus Hospital Québec, QC, Canada
| | - Roxane Pouliot
- Division of Regenerative Medicine, Laval University Experimental Organogenesis Research Center/LOEX, CHU de Québec Research Center - Enfant-Jésus HospitalQuébec, QC, Canada; Faculty of Pharmacy, Laval UniversityQuébec, QC, Canada
| | - Nicolas Dupré
- Neuroscience Division of the CHU de Québec, Department of Medicine of the Faculty of Medicine, Laval University Québec, QC, Canada
| | - Francois Gros-Louis
- Division of Regenerative Medicine, Laval University Experimental Organogenesis Research Center/LOEX, CHU de Québec Research Center - Enfant-Jésus HospitalQuébec, QC, Canada; Department of Surgery, Faculty of Medicine, Laval UniversityQuébec, QC, Canada
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Kim CS, Mitchell IP, Desotell AW, Kreeger PK, Masters KS. Immobilized epidermal growth factor stimulates persistent, directed keratinocyte migration via activation of PLCγ1. FASEB J 2016; 30:2580-90. [PMID: 27025961 DOI: 10.1096/fj.201600252] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 03/21/2016] [Indexed: 01/19/2023]
Abstract
Epidermal growth factor (EGF) is a critical element in dermal repair, but EGF-containing wound dressings have not been successful clinically. However, these dressings have delivered only soluble EGF, and the native environment provides both soluble and matrix-bound EGF. To address our hypothesis that tethered EGF can stimulate cell behaviors not achievable with soluble EGF, we examined single-cell movement and signaling in human immortalized HaCaT keratinocytes treated with soluble or immobilized EGF. Although both EGF treatments increased collective sheet displacement and individual cell speed, only cells treated with immobilized EGF exhibited directed migration, as well as 2-fold greater persistence compared with soluble EGF. Immunofluorescence showed altered EGF receptor (EGFR) trafficking, where EGFR remained membrane-localized in the immobilized EGF condition. Cells treated with soluble EGF demonstrated higher phosphorylated ERK1/2, and cells on immobilized EGF exhibited higher pPLCγ1, which was localized at the leading edge. Treatment with U0126 inhibited migration in both conditions, demonstrating that ERK1/2 activity was necessary but not responsible for the observed differences. In contrast, PLCγ1 inhibition with U73122 significantly decreased persistence on immobilized EGF. Combined, these results suggest that immobilized EGF increases collective keratinocyte displacement via an increase in single-cell migration persistence resulting from altered EGFR trafficking and PLCγ1 activation.-Kim, C. S., Mitchell, I. P., Desotell, A. W., Kreeger, P. K., Masters, K. S. Immobilized epidermal growth factor stimulates persistent, directed keratinocyte migration via activation of PLCγ1.
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Affiliation(s)
- Chloe S Kim
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Isaiah P Mitchell
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Anthony W Desotell
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Pamela K Kreeger
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Kristyn S Masters
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
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Kandhare AD, Alam J, Patil MVK, Sinha A, Bodhankar SL. Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats. PHARMACEUTICAL BIOLOGY 2016; 54:419-32. [PMID: 25894211 DOI: 10.3109/13880209.2015.1038755] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
CONTEXT Wound healing is a consequence of a complex process involving inflammatory, proliferative, and remodeling phases. Naringin, a flavanone glycoside, is associated with modulation of various oxido-inflammatory and growth factors. AIM The aim of this study is to evaluate the wound-healing activity of naringin ointment formulation (NOF) on experimental wound models. MATERIALS AND METHODS A soft paraffin-based cream containing 1, 2, and 4% (w/w) naringin was formulated and evaluated for physicochemical characters. Excision wounds and incisions wounds were used to study the topical effect of NOF for 20 d (once a day) on various biochemical, molecular, and histological parameters. RESULTS NOF (2 and 4%, w/w) treatment showed a significant decrease (p < 0.05) in wound area and epithelization period whereas the rate of wound contraction increased significantly (p < 0.05). The altered levels of oxido-nitrosative stress (SOD, GSH, MDA, MPO, and NO) were significantly (p < 0.05) restored by NOF. Treatment produced a significant increase (p < 0.05) in tensile strength, hydroxyproline content, and protein content. TNF-α, IL-1β, IL-6, IL-8, NF-κB, smad-7, and Bax mRNA expression were significantly down-regulated (p < 0.05) by NOF, whereas polymerase gamma (pol-γ), smad-3, VEGF and TGF-β, and collagen-1 mRNA expressions were significantly up-regulated (p < 0.05) by NOF. Histological alterations in wound skin were also restored by NOF. CONCLUSION NOF exerts wound healing potential via down-regulated expression of inflammatory (NF-κB, TNF-α, and ILs), apoptotic (pol-γ and Bax), and up-regulated growth factor (VEGF and TGF-β) expression, thus modulating collagen-1 expression to induce angiogenesis leading to wound healing.
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Affiliation(s)
- Amit D Kandhare
- a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India
| | - Javed Alam
- a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India
| | - Mithun V K Patil
- a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India
| | - Akanksha Sinha
- a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India
| | - Subhash L Bodhankar
- a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India
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Wound Healing Effects of Persian Oak (Quercus brantii) Ointment in Rats. Jundishapur J Nat Pharm Prod 2015. [DOI: 10.5812/jjnpp.55292] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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An Y, Ma C, Tian C, Zhao L, Pang L, Tu Q, Xu J, Wang J. On-chip assay of the effect of topographical microenvironment on cell growth and cell-cell interactions during wound healing. BIOMICROFLUIDICS 2015; 9:064112. [PMID: 26649132 PMCID: PMC4670448 DOI: 10.1063/1.4936927] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Accepted: 11/19/2015] [Indexed: 06/05/2023]
Abstract
Wound healing is an essential physiological process for tissue homeostasis, involving multiple types of cells, extracellular matrices, and growth factor/chemokine interactions. Many in vitro studies have investigated the interactions between cues mentioned above; however, most of them only focused on a single factor. In the present study, we design a wound healing device to recapitulate in vivo complex microenvironments and heterogeneous cell situations to investigate how three types of physiologically related cells interact with their microenvironments around and with each other during a wound healing process. Briefly, a microfluidic device with a micropillar substrate, where diameter and interspacing can be tuned to mimic the topographical features of the 3D extracellular matrix, was designed to perform positional cell loading on the micropillar substrate, co-culture of three types of physiologically related cells, keratinocytes, dermal fibroblasts, and human umbilical vein endothelial cells, as well as an investigation of their interactions during wound healing. The result showed that cell attachment, morphology, cytoskeleton distribution, and nucleus shape were strongly affected by the micropillars, and these cells showed collaborative response to heal the wound. Taken together, these findings highlight the dynamic relationship between cells and their microenvironments. Also, this reproducible device may facilitate the in vitro investigation of numerous physiological and pathological processes such as cancer metastasis, angiogenesis, and tissue engineering.
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Affiliation(s)
| | - Chao Ma
- Colleges of Science and Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi 712100, People's Republic of China
| | - Chang Tian
- Colleges of Science and Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi 712100, People's Republic of China
| | - Lei Zhao
- Colleges of Science and Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi 712100, People's Republic of China
| | - Long Pang
- Colleges of Science and Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi 712100, People's Republic of China
| | - Qin Tu
- Colleges of Science and Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi 712100, People's Republic of China
| | - Juan Xu
- Colleges of Science and Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi 712100, People's Republic of China
| | - Jinyi Wang
- Colleges of Science and Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi 712100, People's Republic of China
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Nayak KK, Gupta P. In vitro biocompatibility study of keratin/agar scaffold for tissue engineering. Int J Biol Macromol 2015; 81:1-10. [DOI: 10.1016/j.ijbiomac.2015.07.025] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2015] [Revised: 06/07/2015] [Accepted: 07/12/2015] [Indexed: 12/22/2022]
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Mittal A, Kumar N. A new, bioactive, antibacterial-eluting, composite graft for infection-free wound healing. Wound Repair Regen 2015; 22:527-36. [PMID: 24899130 DOI: 10.1111/wrr.12194] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2013] [Accepted: 04/01/2014] [Indexed: 11/28/2022]
Abstract
The current work focuses on the in vivo performance of a newly developed injectable composite graft in infected full-thickness wounds. The composite graft was composed of bioactive porous Poly dl-lactide-co-glycolide scaffolds, antibiotic gentamicin, and crosslinked gelatin as carrier gel. Treated infected wounds exhibited a faster wound closure, rapid weight gain, lower neutrophil count, higher breaking strength, and 100 times lesser microbial count (10(2) colony forming units/g in infected treated vs. 10(4) colony forming units/g in infected control group) in comparison with infected control group 28 days post treatment. During healing, collagen production was more in the treated groups at day 7 than controls and thereafter gradually reduced to normal levels. Histology revealed a mature scar tissue formation, fibroblast proliferation, epidermal resurfacing, and collagen deposition in reticular alignment similar to normal healthy skin in treated wounds. Further, the plasma concentration of gentamicin was 35-45 μg/mL during the initial 12 hours and reduced to 1 μg/mL in 24 hours, which indicated safe levels of the antibiotic drug during healing. These results clearly indicate a faster, infection-free, and safe after treatment with the developed graft.
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Affiliation(s)
- Anupama Mittal
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, India
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Kandhare AD, Ghosh P, Bodhankar SL. Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats. Chem Biol Interact 2014; 219:101-12. [DOI: 10.1016/j.cbi.2014.05.012] [Citation(s) in RCA: 111] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Revised: 05/13/2014] [Accepted: 05/20/2014] [Indexed: 12/19/2022]
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Anti-microRNA-378a enhances wound healing process by upregulating integrin beta-3 and vimentin. Mol Ther 2014; 22:1839-50. [PMID: 24954475 PMCID: PMC4428398 DOI: 10.1038/mt.2014.115] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Accepted: 06/12/2014] [Indexed: 01/11/2023] Open
Abstract
Delayed or impaired wound healing is a major public health issue worldwide,
especially in patients with diabetes mellitus and vascular atherosclerosis.
MicroRNAs have been identified as key regulators of wound healing. Here, we show
that miR-Pirate378a transgenic mice (and thus have inhibited miR-378a-5p
function) display enhanced wound healing. Expression of vimentin and β3
integrin, two important modulators of wound healing, is markedly elevated in the
transgenic mice. MiR-Pirate378a-transfected cells display greater mobility
during migration assays, which was hypothesized to be due to the upregulation of
vimentin and β3 integrin. Both molecules were confirmed to be targets of
miR-378a, and thus their expression could be rescued by miR-Pirate378a.
Overexpression of vimentin also contributed to fibroblast differentiation, and
upregulation of β3 integrin was responsible for increased angiogenesis.
Mice treatment with miR-Pirate378a-conjugated nanoparticles displayed enhanced
wound healing. Thus, we have demonstrated that knockdown of miR-378a increased
the expression of its target proteins, vimentin, and β3 integrin, which
accelerated fibroblast migration and differentiation in vitro and
enhanced wound healing in vivo.
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Bonvallet PP, Culpepper BK, Bain JL, Schultz MJ, Thomas SJ, Bellis SL. Microporous dermal-like electrospun scaffolds promote accelerated skin regeneration. Tissue Eng Part A 2014; 20:2434-45. [PMID: 24568584 DOI: 10.1089/ten.tea.2013.0645] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The goal of this study was to synthesize skin substitutes that blend native extracellular matrix (ECM) molecules with synthetic polymers which have favorable mechanical properties. To this end, scaffolds were electrospun from collagen I (col) and poly(ɛ-caprolactone) (PCL), and then pores were introduced mechanically to promote fibroblast infiltration, and subsequent filling of the pores with ECM. A 70:30 col/PCL ratio was determined to provide optimal support for dermal fibroblast growth, and a pore diameter, 160 μm, was identified that enabled fibroblasts to infiltrate and fill pores with native matrix molecules, including fibronectin and collagen I. Mechanical testing of 70:30 col/PCL scaffolds with 160 μm pores revealed a tensile strength of 1.4 MPa, and the scaffolds also exhibited a low rate of contraction (<19%). Upon implantation, scaffolds should support epidermal regeneration; we, therefore, evaluated keratinocyte growth on fibroblast-embedded scaffolds with matrix-filled pores. Keratinocytes formed a stratified layer on the surface of fibroblast-remodeled scaffolds, and staining for cytokeratin 10 revealed terminally differentiated keratinocytes at the apical surface. When implanted, 70:30 col/PCL scaffolds degraded within 3-4 weeks, an optimal time frame for degradation in vivo. Finally, 70:30 col/PCL scaffolds with or without 160 μm pores were implanted into full-thickness critical-sized skin defects. Relative to nonporous scaffolds or sham wounds, scaffolds with 160 μm pores induced accelerated wound closure, and stimulated regeneration of healthy dermal tissue, evidenced by a more normal-appearing matrix architecture, blood vessel in-growth, and hair follicle development. Collectively, these results suggest that microporous electrospun scaffolds are effective substrates for skin regeneration.
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Affiliation(s)
- Paul P Bonvallet
- 1 Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham , Birmingham, Alabama
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Ghori V, Mandavia DR, Patel TK, Tripathi CB. Effect of topical nitric oxide donor (0.2 % glyceryl trinitrate) on wound healing in diabetic wistar rats. Int J Diabetes Dev Ctries 2014; 34:45-49. [DOI: 10.1007/s13410-013-0138-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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Agra IKR, Pires LLS, Carvalho PSM, Silva-Filho EA, Smaniotto S, Barreto E. Evaluation of wound healing and antimicrobial properties of aqueous extract from Bowdichia virgilioides stem barks in mice. AN ACAD BRAS CIENC 2014; 85:945-54. [PMID: 23969849 DOI: 10.1590/s0001-37652013005000049] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Accepted: 10/19/2011] [Indexed: 11/22/2022] Open
Abstract
The decoction of the stem barks from Bowdichia virgilioides KUNTH is a folk remedy used to treat inflammatory disorders in Latin American and Brazil. In the present study, the wound healing activity of aqueous extract of the stem bark from B. virgilioides, called AEBv, was evaluated by the rate of healing by wound contraction and period of epithelization at different days post-wound using the wound excisional model. On day 9, the AEBv-treated animals exhibited significative reduction in the wound area when compared with controls. In wound infected with S. aureus, the AEBv significantly improved the wound contraction when compared to the saline-treated mice. The histological analysis showed that AEBv induced a collagen deposition, increase in the fibroblast count and few inflammatory cells than compared to saline-treated group. The expression of collagen type I was increased in the group treated with AEBv as indicated by immunohistochemical staining. In vitro, the AEBv was effective only against S. aureus but not against P. aeruginosa. Together, the results of this study demonstrate, for the first time, the healing and antimicrobiological effects of aqueous extract of the stem bark from B. virgilioides in the therapy of skin wounds.
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Affiliation(s)
- Isabela K R Agra
- Laboratório de Biologia Celular, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Campus A.C. Simões, 57072-970 Maceió Al, Brasil
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