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Zoheir KMA, Ali NI, Ashour AE, Kishta MS, Othman SI, Rudayni HA, Rashad AA, Allam AA. Lipoic acid improves wound healing through its immunomodulatory and anti-inflammatory effects in a diabetic mouse model. J Diabetes Metab Disord 2025; 24:56. [PMID: 39868353 PMCID: PMC11759746 DOI: 10.1007/s40200-025-01559-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 10/28/2024] [Indexed: 01/28/2025]
Abstract
Objectives Diabetes mellitus is a chronic disease that has become more prevalent worldwide because of lifestyle changes. It leads to serious complications, including increased atherosclerosis, protein glycosylation, endothelial dysfunction, and vascular denervation. These complications impair neovascularization and wound healing, resulting in delayed recovery from injuries and an elevated risk of infections. The present study aimed to investigate the effect of lipoic acid (LA) on the key mediators involved in the wound healing process, specifically CD4 + CD25 + T cell subsets, CD4 + CD25 + Foxp3 + regulatory T (Treg) cells, T-helper-17 (Th17) cells that generate IL-17 A, glucocorticoid-induced tumor necrosis factor receptor (GITR) expressing cells, as well as cytokines such as IL-2, IL-1β, IL-6, and TNF-α and IFN-γ. These mediators play crucial roles in epidermal and dermal proliferation, hypertrophy, and cell migration. Methods We divided mice into 5 groups: the non-diabetic (normal control; NC), wounded non-diabetic mice (N + W), wounded diabetic mice (D + W), wounded diabetic mice treated with 50 mg/kg lipoic acid (D + W + L50) for 14 days, and wounded diabetic mice treated with 100 mg/kg lipoic acid (D + W + L100) for 14 days. Results Flow cytometric analysis indicated that lipoic acid-treated mice exhibited a significant decrease in the frequency of intracellular cytokines (IL-17 A, TNF-α and IFN-γ) in CD4 + T cells, as well as a reduction in the number of GITR-expressing cells. Conversely, a significant upregulation in the number CD4+, CD25+, FOXp3 + and CD4 + CD25 + Foxp3 + regulatory T (Treg) cells was observed in this group compared to both the normal + wounded (N + W) and diabetic + wounded (D + W) groups. Additionally, the mRNA Levels of inflammatory mediators (IL-2, IL-1β, IL-6, and TNF-α) were downregulated in lipoic acid-treated mice compared to other groups. T thereby he histological findings of diabetic skin wounds treated with lipoic acid showed well-healed surgical wounds. Conclusions These findings support the beneficial role of lipoic acid in fine-tuning the balance between anti-inflammatory and pro-inflammatory cytokines, influencing both their release and gene expression.
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Affiliation(s)
- Khairy M. A. Zoheir
- Cell Biology Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza 12622 Egypt
| | - Neama I. Ali
- Cell Biology Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza 12622 Egypt
| | - Abdelkader E. Ashour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Salman International University, Ras Sudr, South Sinai Egypt
| | - Mohamed S. Kishta
- Hormones Department, Medical Research and Clinical Studies Institute, and Stem Cell Lab, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo, 12622 Egypt
| | - Sarah I. Othman
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. BOX 84428, 11671 Riyadh, Saudi Arabia
| | - Hassan A. Rudayni
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, 11623 Saudi Arabia
| | - Ahmed A. Rashad
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829 Egypt
| | - Ahmed A. Allam
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, 11623 Saudi Arabia
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Abdel-Monem DA, Sabry SA, Ghozlan HA, Zaghloul EH. Preparation of Novel Marine Enterococcus faecium MSD8 Exopolysaccharide Ointment and In Vivo Evaluation of Its Impact on Cutaneous Wound Healing in Male Albino Rats. Probiotics Antimicrob Proteins 2025; 17:963-975. [PMID: 39133428 PMCID: PMC12055640 DOI: 10.1007/s12602-024-10334-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2024] [Indexed: 08/13/2024]
Abstract
The current study describes the isolation of exopolysaccharide (EPS) producing lactic acid bacteria (LAB) from marine samples and testing different sugar additives with different proportions for enhanced EPS yield. The isolate MSD8 showed the most potential, yielding 200 mg/L of EPS after being cultivated at 37 °C for 48 h on de Man Rogosa and Sharpe medium (MRS) supplemented with 3% sucrose. The marine isolate MSD8 was identified as Enterococcus faecium with 99.58% probability using 16S rRNA gene sequencing. The obtained sequence was deposited in GenBank and assigned the accession number MW924065. The feature of MSD8-EPS was characterized by estimating the total carbohydrate content by UV-vis to be ~ 71%. The FTIR analysis further indicated the presence of characteristic bands of polysaccharide. The cytotoxicity of the produced MSD8-EPS was assessed using human skin fibroblasts (HSF). The IC50 was determined to be > 100 μg/mL, which signifies that MSD8-EPS is safe for skin application. The produced EPS was used to prepare a novel ointment, which was tested for wound healing ability in male albino rats. The ointment significantly (P ≤ 0.05) shortened the time needed for wound healing, as it successfully healed the wounds by 94.93% on the 7th day and completely (100%) healed the wound by the 12th day. In comparison, the control group was healed by 73.2% and 84.83%, respectively. The data confirm that the prepared ointment can safely be used for pharmaceutical wound care products.
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Affiliation(s)
- Doaa A Abdel-Monem
- Botany and Microbiology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Soraya A Sabry
- Botany and Microbiology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Hanan A Ghozlan
- Botany and Microbiology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
| | - Eman H Zaghloul
- National Institute of Oceanography and Fisheries (NIOF), Cairo, Egypt.
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Schmidt A, von Woedtke T, Weltmann KD, Bekeschus S. YAP/TAZ, beta-catenin, and TGFb pathway activation in medical plasma-induced wound healing in diabetic mice. J Adv Res 2025; 72:387-400. [PMID: 38986808 DOI: 10.1016/j.jare.2024.07.004] [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: 05/01/2024] [Revised: 06/15/2024] [Accepted: 07/06/2024] [Indexed: 07/12/2024] Open
Abstract
INTRODUCTION Hippo is a signaling pathway that is evolutionarily conserved and plays critical roles in wound healing and tissue regeneration. Disruption of the transcriptional activity of both Hippo-associated factors, the yes-associated protein (YAP), and the transcriptional co-activator with PDZ binding motif (TAZ) has been associated with cardiovascular diseases, fibrosis, and cancer. This makes the Hippo pathway an appealing target for therapeutic interventions. OBJECTIVES Prior research has indicated that medical gas plasma promotes wound healing by delivering a combination of reactive species directly to the affected areas. However, the involvement of YAP/TAZ and other signaling pathways in diabetic wound healing remains unexplored. METHODS To this extent, ear wounds were generated and treated with gas plasma in streptozotocin (STZ)-induced diabetic mice. Transcriptome profiling at two wound healing stages (days 9 and 20 post-wounding) was performed in female and male mice. Additionally, we employed gene and protein expression analyses, utilizing immunohistological and -chemical staining of various targets as well as quantitative PCR and Western blot analysis. RESULTS Gas plasma treatment accelerated healing by increasing re-epithelialization and modifying extracellular matrix components. Transcriptomic profiling charting the major alterations in gene expression following plasma treatment was followed by a validation of several targets using transcriptional and translational quantification as well as localization analyses. CONCLUSION Our study evaluated the cellular regulation of essential targets of the Hippo and related pathways such as YAP/TAZ, β-catenin, tumor growth factor β, and oxidative stress signaling after plasma treatment. The activation of genes, pathways, and their regulators is an attractive therapeutic aim for a therapeutic intervention in dermal skin repair in diabetic diseases using medical gas plasmas.
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Affiliation(s)
- Anke Schmidt
- ZIK plasmatis, Leibniz-Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Technologies Research Alliance, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.
| | - Thomas von Woedtke
- ZIK plasmatis, Leibniz-Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Technologies Research Alliance, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany; Institute for Hygiene and Environmental Medicine, Greifswald University Medical Center, Sauerbruchstr., 17475 Greifswald, Germany
| | - Klaus-Dieter Weltmann
- ZIK plasmatis, Leibniz-Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Technologies Research Alliance, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany
| | - Sander Bekeschus
- ZIK plasmatis, Leibniz-Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Technologies Research Alliance, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany; Department of Clinic and Policlinic for Dermatology and Venerology, Rostock University Medical Center, Strempelstr. 13, 18057 Rostock, Germany.
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Siewe N, Friedman A. Modeling treatment of diabetic wounds with oxygen therapy and senolytic drug. Sci Rep 2025; 15:17944. [PMID: 40410445 PMCID: PMC12102321 DOI: 10.1038/s41598-025-02852-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 05/16/2025] [Indexed: 05/25/2025] Open
Abstract
Diabetic wounds are common in patients with type 2 diabetes; they are ischemic and inflammatory, and difficult to heal without intervention. Hyperbaric oxygen therapy (HBOT) is a standard treatment, but its effectiveness is limited to a subset of the aging population. Senescent fibroblasts, a hallmark of aging, impair wound healing, and senolytic drugs, like quercetin (Q), which target senescent cells, may improve healing. In this study, we developed a mathematical model that defines biological aging through two parameters, η and [Formula: see text], that decline with age. These parameters reflect the biological age of an individual, where η represents fibroblast proliferation and [Formula: see text] represents the production of the angiogenetic protein VEGF. Our model predicts that treatment with only HBOT achieves wound closure, within normal expectable time, for patients with a limited subset pairs of [Formula: see text], and this subset is increased to a larger subset by combining Q with HBOT. The two subsets of [Formula: see text] are determined explicitly by simulations of the model. To make these results applicable in clinical setting, one will have to relate the aging parameters η and [Formula: see text] to tangible marks of biological-aging factors.
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Affiliation(s)
- Nourridine Siewe
- School of Mathematics and Statistics, Rochester Institute of Technology, Rochester, NY, USA.
| | - Avner Friedman
- Department of Mathematics, The Ohio State University, Columbus, OH, USA
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Sarkar S, Choudhari AP, Mukherjee A, Rathi V, Das B, Poundarik AA. 3D Printed Human Amnion-Based Bioactive Hybrid Dressings for Effective Management of Complex Infected Wounds. ACS APPLIED MATERIALS & INTERFACES 2025. [PMID: 40393009 DOI: 10.1021/acsami.5c06672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Abstract
Chronic wounds are often afflicted with persistent infection, excessive exudate accumulation, and delayed healing, leading to prolonged hospitalization. Excess moisture overhydrates the wound, promotes infection, and causes edema. Peri-wound skin may develop rashes, immersion injuries, and epidermal detachment. Nutrient-rich exudates foster microbial growth, increasing the infection risk. High bacterial loads lead to crust formation, continuous leakage, and foul odor, further complicating healing. To address this challenge, we developed a 3D printed amnion-based hybrid dressing comprising a regenerative layer integrated with a laminated silver-embedded polyurethane foam layer for partial and full thickness (thickness 0.12 mm-4 mm) infected wounds and burns. This dressing can suffice the varied clinical requirements of wound management by augmenting tissue regeneration, reducing bacterial load, and managing wound exudate. Human amnion was processed through decellularization and lyopreservation. Key angiogenic growth factors VEGF-A (54.12 ± 2.31 pg/mg) and PDGF-BB (3.760 ± 0.14 pg/mg) were quantified. Long-term in vitro cell viability was assessed for 20 days (as per ISO 10993-5 standards). Bioink was formulated using cryo-milled amnion particles and excipients optimized through rheology. Hybrid dressing was developed using an extrusion-based 3D printer, layering the amnion bioink onto the physical substrate, followed by lyophilization and gamma sterilization. Preclinical efficacy was assessed using a rodent Staphylococcus aureus-infected wound model, comparing the hybrid dressing to an in-house-developed amnion-mupirocin (AM) powder formulation with standard of care dressing. Both treatments demonstrated comparable wound closure rates and a significant bacterial load reduction. However, hybrid dressing offered superior healed tissue quality, increased CD31 expression, and improved neovascularization compared to AM powder treatment with a temporally regulated CD31 expression pattern mirroring the natural healing progression. This can be attributed to the hybrid construct of the dressing that provides effective exudate management, preventing its accumulation that could otherwise hinder angiogenesis, along with replenishment of wound bed with regenerative factors, aiding in mimicking the natural healing cascades.
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Affiliation(s)
- Satarupa Sarkar
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Ropar, Punjab 140001, India
| | - A Pratap Choudhari
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Ropar, Punjab 140001, India
| | - Anwesha Mukherjee
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Ropar, Punjab 140001, India
| | - Varun Rathi
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Ropar, Punjab 140001, India
| | - Bodhisatwa Das
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Ropar, Punjab 140001, India
| | - Atharva A Poundarik
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Ropar, Punjab 140001, India
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Don TM, Lee KT, Chen BY, Tang S, Huang YC, Chuang AEY. Physicochemical properties of bacterial cellulose/phototherapeutic polypyrrole/antibacterial chitosan composite membranes and their evaluation as chronic wound dressings. Int J Biol Macromol 2025; 308:142183. [PMID: 40107531 DOI: 10.1016/j.ijbiomac.2025.142183] [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: 07/22/2024] [Revised: 03/04/2025] [Accepted: 03/14/2025] [Indexed: 03/22/2025]
Abstract
Bacterial cellulose (BC) is a natural fiber membrane and has been applied in many biomedical applications. Herein, it was used as the main scaffold to prepare wound dressings for treating diabetic skin wounds. Polypyrrole (PPy) was first synthesized by in situ oxidative polymerization within BC membrane and applied as a photothermal agent, followed by coating with chitosan (CS) to improve the biocompatibility and antibacterial properties. SEM pictures revealed sub-micron PPy particles ranging from 100 to 200 nm were formed and attached to the BC fibrils, whereas CS formed a thin, porous layer on the surface. FTIR analysis showed that there was hydrogen bonding between BC, PPy and CS components. The crystalline structure of BC was maintained yet with decreased crystallinity by addition of PPy and CS. The water absorption capability and water vapor transmission rate decreased by PPy incorporation owing to its hydrophobic nature, but they were regained by addition of hydrophilic CS. The prepared BC/PPy/CS membrane was biocompatible toward L929 cells and maintained hemocompatibility. Additionally, both PPy and CS contributed to the antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, while they demonstrated a potential for synergistic antibacterial effects when combined. Finally, the near-infrared (NIR)-driven photothermal-hyperthermic effects by PPy on lesions upregulated heat-shock protein (HSP) expression and anti-inflammatory properties by CS boosted restoration of diabetic wounds in vivo without the addition of any antibiotics or anti-inflammatory drugs. The results thus support using the BC/PPy/CS membrane for diabetic wound regeneration.
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Affiliation(s)
- Trong-Ming Don
- Department of Chemical and Materials Engineering, Tamkang University, New Taipei City, Taiwan.
| | - Kuan-Ting Lee
- Department of Chemical and Materials Engineering, Tamkang University, New Taipei City, Taiwan.
| | - Bo-Yi Chen
- Department of Chemical and Materials Engineering, Tamkang University, New Taipei City, Taiwan.
| | - Shuoheng Tang
- Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan
| | - Yi-Cheng Huang
- Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.
| | - Andrew E-Y Chuang
- Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan.
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Chetty R, Bhagwan R, Govender N. The biopsychosocial effects of transtibial amputation: A South African perspective. Afr J Disabil 2025; 14:1404. [PMID: 40357351 PMCID: PMC12067012 DOI: 10.4102/ajod.v14i0.1404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 12/15/2024] [Indexed: 05/15/2025] Open
Abstract
Background A myriad of physical, psychosocial and environmental sequelae are associated with limb loss. However, there is a paucity of empirical South African data, which focusses on these sequelae, how they interface with the amputee's quality of life as well as the challenges they experience following amputation. Objectives This study sought to explore the biopsychosocial effects of amputation and how it affected the quality of life of transtibial amputees. Method A qualitative approach guided this study. Data were collected using one-on-one interviews with 14 unilateral transtibial amputees. Data were analysed thematically. Results Five broad themes emerged from the inquiry, which captured amputees' experiences of phantom limb pain, body image disturbances and their challenges related to adapting to daily activities. Participants also expressed the salience of familial support as well as the importance of psychological interventions to cope. Conclusion The findings suggested that support networks and professional psychological intervention are imperative in facilitating successful adjustment to the amputation experience. Raising awareness of limb loss, in both rural and urban settings, may help reduce the stigma attached to it. Contribution Quality of life comprises several domains, namely physical, psychological, environmental and social. However, limited local and international data exists regarding the environmental and social effects. This study brought to the fore the positive and negative effects of amputation in each domain, as well as various strategies, which facilitate successful adjustment to amputation.
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Affiliation(s)
- Riyona Chetty
- Department of Medical Orthotics and Prosthetics, Faculty of Health Sciences, Durban University of Technology, Durban, South Africa
| | - Raisuyah Bhagwan
- Department of Community Health Studies, Faculty of Health Sciences, Durban University of Technology, Durban, South Africa
| | - Nalini Govender
- Department of Basic Medical Sciences, Faculty of Health Sciences, Durban University of Technology, Durban, South Africa
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Imchen L, Manisekaran R, Jamir I, Rathore HS, Senthilvelan T. A review on plant-mediated synthesis of AgNPs and their formulations for wound healing application. Mol Biol Rep 2025; 52:419. [PMID: 40266399 DOI: 10.1007/s11033-025-10512-4] [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: 08/04/2024] [Accepted: 04/14/2025] [Indexed: 04/24/2025]
Abstract
Wound healing is a sophisticated and dynamic process carried out by a myriad of cellular activities that work together in a coordinated manner to effectively repair damaged tissue. It involves a cascade process involving hemostasis, inflammation, granulation, maturation, and remodeling. However, in the case of chronic wounds, owing to the delayed wound healing process, various microbes invade the wound area and produce biofilms that hinder the healing process. Owing to rapid advancements in nanotechnology, several nanomaterials with diverse formulations have been investigated for wound healing. Among them, silver nanoparticles (AgNPs) have shown excellent properties, as they have unique physiochemical properties that address the problems associated with wound healing. The antibacterial and antioxidant properties of silver greatly enhance wound-care diagnostics. The use of medicinal plants for green synthesis of AgNPs has been widely researched, with these plants serving as both reducing and stabilizing agents in the nanoparticle formation process. This review focuses on different wound types, problems related to wounds, green-synthesized AgNPs using medicinal plants, and their limitations and advantages in wound dressing formulations. This study aims to provide the scientific community with a directional view in analyzing the role and importance of green-synthesized AgNPs in wound care.
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Affiliation(s)
- Lolenmenla Imchen
- Department of Biotechnology, School of Engineering and Technology, Nagaland University, Meriema, Kohima, Nagaland, 797004, India
| | - Ravichandran Manisekaran
- Interdisciplinary Research Laboratory (LII), Nanostructures & Biomaterials, Escuela Nacional de Estudios Superiores (ENES) Unidad León-Universidad Nacional Autónoma de México (UNAM), León, Guanajuato, C.P. 37689, Mexico
| | - Imlitoshi Jamir
- Department of Biotechnology, School of Engineering and Technology, Nagaland University, Meriema, Kohima, Nagaland, 797004, India
| | - Hanumant Singh Rathore
- Department of Biotechnology, School of Engineering and Technology, Nagaland University, Meriema, Kohima, Nagaland, 797004, India.
| | - T Senthilvelan
- Department of Bioinformatics, Saveetha School of Engineering (SSE), Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, 602105, India.
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Wang L, Nie F, Lu Z, Chong Y. Mechanism underlying the involvement of CXCR4/CXCL12 in diabetic wound healing and prospects for responsive hydrogel-loaded CXCR4 formulations. Front Pharmacol 2025; 16:1561112. [PMID: 40308758 PMCID: PMC12040920 DOI: 10.3389/fphar.2025.1561112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Accepted: 04/07/2025] [Indexed: 05/02/2025] Open
Abstract
Diabetes mellitus is a prevalent chronic disease, often leading to complications, with chronic wounds being among the most challenging. Impairment of the CXCR4/CXCL12 signaling pathway, which plays a key role in cell mobilization, migration, and angiogenesis, significantly hampers the wound healing process in diabetic patients. Modulation of this pathway using CXCR4-targeted agents has shown promise in restoring wound repair capabilities. Additionally, the development of responsive hydrogels capable of adapting to external stimuli offers a powerful platform for drug delivery in chronic wound management. These hydrogels, when loaded with CXCR4 agonists or antagonists, enable controlled drug release and real-time therapeutic modulation. Integrating such hydrogels with existing wound healing strategies may provide an innovative and effective solution for overcoming the challenges associated with diabetic wound treatment.
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Affiliation(s)
- Lingli Wang
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Fengsong Nie
- Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Zhaoyu Lu
- Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yang Chong
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, China
- Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
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Schmidt A, Miebach L, Bagli C, Kantz L, Emmert S, von Woedtke T, Bekeschus S. Medical gas plasma modifies Nrf2 signaling in diabetic wound healing. J Adv Res 2025:S2090-1232(25)00264-4. [PMID: 40250557 DOI: 10.1016/j.jare.2025.04.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 04/01/2025] [Accepted: 04/15/2025] [Indexed: 04/20/2025] Open
Abstract
INTRODUCTION Diabetes mellitus is a chronic disease that can disrupt physiologic wound healing. Medical gas plasma technology produces therapeutic reactive species that support wound healing. OBJECTIVE Previous studies have shown that increasing the transcriptional activity of the redox regulator nuclear factor erythroid 2-related factor 2 (Nrf2) in diabetic models can improve insulin sensitivity, reduce blood glucose levels, and ameliorate diabetic complications. However, the therapeutic potential and mechanisms of action of gas plasma have not been addressed in this context. METHODS Full-thickness dermal ear wounds were created in a preclinical mouse model of type II diabetes and compared with a native wild-type strain of C57BL/6 mice. First, the formation of reactive species in the plasma gas phase was determined by optical emission spectroscopy. Second, qPCR, protein expression, and inflammation analysis by cytokine secretion were performed to confirm the transcriptional results. Finally, qPCR and cytokine profiling were conducted to measure the effects of gas plasma in patient wound samples. RESULTS Repeated in vivo treatment with medical gas plasma supported wound healing, e.g., re-epithelialization, in both sexes. Gas plasma-stimulated changes in Nrf2 signaling associated with downstream targets were supported by the evidence of impaired wound healing in Nrf2 knockout mice. In addition, gas plasma treatment significantly affected inflammation by modulating local and systemic cytokine levels. In vivo, treatment of human diabetic wounds underscored the involvement of Nrf2 signaling in protecting against oxidative stress, as assessed by qPCR. The cytokine signature of human diabetic wounds outlined different response patterns among patients after a single exposure, while inflammatory mediators were consistently reduced after repeated plasma treatment. CONCLUSIONS The present finding of accelerated wound healing by the Nrf2 activator underlines the high potential of medical gas plasma therapy in non-diabetic and diabetic wound healing.
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Affiliation(s)
- Anke Schmidt
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Research Alliance, Felix-Hausdorff-Str. 2, Greifswald 17489, Germany
| | - Lea Miebach
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Research Alliance, Felix-Hausdorff-Str. 2, Greifswald 17489, Germany
| | - Can Bagli
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Research Alliance, Felix-Hausdorff-Str. 2, Greifswald 17489, Germany
| | - Liane Kantz
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Research Alliance, Felix-Hausdorff-Str. 2, Greifswald 17489, Germany
| | - Steffen Emmert
- Department of Dermatology and Venereology, University Medical Center Rostock, Strempelstr. 13, Rostock 18057, Germany
| | - Thomas von Woedtke
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Research Alliance, Felix-Hausdorff-Str. 2, Greifswald 17489, Germany; Institute of Hygiene and Environmental Medicine, Greifswald University Medical Center, Sauerbruchstr., Greifswald 17475, Germany
| | - Sander Bekeschus
- ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Research Alliance, Felix-Hausdorff-Str. 2, Greifswald 17489, Germany; Department of Dermatology and Venereology, University Medical Center Rostock, Strempelstr. 13, Rostock 18057, Germany.
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Miya MB, Ashutosh, Maulishree, Dey D, Pathak V, Khare E, Kalani K, Chaturvedi P, Singh V, Chaturvedi P, Kalani A. Accelerated diabetic wound healing using a chitosan-based nanomembrane incorporating nanovesicles from Aloe barbadensis, Azadirachta indica, and Zingiber officinale. Int J Biol Macromol 2025; 310:143169. [PMID: 40239792 DOI: 10.1016/j.ijbiomac.2025.143169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 04/08/2025] [Accepted: 04/13/2025] [Indexed: 04/18/2025]
Abstract
Diabetic wounds pose a substantial clinical challenge due to delayed healing, persistent inflammation, and susceptibility to infections. This study investigates the therapeutic efficacy of a chitosan-polyvinyl alcohol nanomembrane (OXY-NMAloe) plant-derived extracellular vesicles enriched with extracellular vesicles derived from Aloe barbadensis, Azadirachta indica, and Zingiber officinale. Chitosan, a natural biological macromolecule, forms the nanomembrane's matrix, contributing to its flexibility, porosity, and structural integrity, essential for maintaining optimal wound hydration and supporting tissue regeneration. In in vivo studies on streptozotocin-induced diabetic rats, OXY-NMAloe significantly accelerated wound closure by approximately 23 % compared to just 7 % in the control-treated group, even after one day. This effect was achieved by modulating pro-inflammatory cytokines, activating collagen synthesis, and restoring mitochondrial function. The membrane also inhibited matrix metalloproteinase overexpression, reducing excessive extracellular matrix degradation by ~40 % and promoting tissue regeneration. Furthermore, OXY-NMAloe demonstrated potent antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, decreasing microbial colonization and fostering a favorable healing environment. By integrating the structural properties of chitosan with the bioactivity of plant-derived extracellular vesicles, the nanomembrane offers a multifunctional therapeutic platform for accelerating tissue repair and addressing key challenges in diabetic wound management.
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Affiliation(s)
- Mumtaj Bano Miya
- Disease Biology Lab, Department of Life Science and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, India
| | - Ashutosh
- Disease Biology Lab, Department of Life Science and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, India
| | - Maulishree
- Disease Biology Lab, Department of Life Science and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, India
| | - Dhananjay Dey
- Chemistry Lab, Department of Basic Sciences, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, India
| | - Vandana Pathak
- Disease Biology Lab, Department of Life Science and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, India
| | - Ekta Khare
- Microbiology Lab, Department of Microbiology, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, India
| | - Komal Kalani
- Vestaron Corporation, Raleigh, Durham 27709, NC, USA
| | | | - Vimal Singh
- School of Education, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, India
| | - Pankaj Chaturvedi
- Department of Physiology, University of Louisville, Louisville 40202, KY, USA
| | - Anuradha Kalani
- Disease Biology Lab, Department of Life Science and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur 208024, India; Department of Physiology, University of Louisville, Louisville 40202, KY, USA.
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12
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Azari Z, Sadeghi-Avalshahr A, Alipour F, Kondori BJ, Askari VR, Mollazadeh S, Nazarnezhad S, Nasiri SN, Kermani F, Ranjbar-Mohammadi M. Advanced nanofibers integrating vitamin D3 and cerium oxide nanoparticles for enhanced diabetic wound healing: Co-electrospun silk fibroin-collagen and chitosan-PVA systems. Int J Biol Macromol 2025; 310:143099. [PMID: 40222506 DOI: 10.1016/j.ijbiomac.2025.143099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 04/03/2025] [Accepted: 04/10/2025] [Indexed: 04/15/2025]
Abstract
This study investigates the co-electrospinning of polyvinyl alcohol-chitosan (PVA-CS) with cerium oxide nanoparticles (CeNPs) and silk fibroin-collagen (SF-Col) with vitamin D3 for diabetic wound healing applications. The SEM results showed smooth, bead-free nanofiber structures. The diameters of the SF-Col and PVA-CS nanofibers ranged from 168 ± 51 nm to 1956 ± 450 nm and 211.4 ± 37.2 nm, respectively. By surface modification using fetal bovine serum (FBS), CeNPs dispersion was enhanced. The average diameter of the uniformly distributed fibers on the SF-Co-D/PVA-CS-CeNPs nanofibers was 621.4 ± 50.6 nm. The addition of CeNPs and vitamin D3 improved cytocompatibility at lower doses. The FTIR test confirmed polymer interactions. Contact angle measurements indicated increased hydrophilicity. SEM analysis demonstrated excellent adhesion and growth of L929 fibroblast cells and significant HUVEC migration on SF-Col-D/PVA-CS-CeNP mats, emphasizing their potential to support cell proliferation and tissue regeneration. Blood compatibility assays exhibited hemolysis percentages below 2 %, classifying the nanofibers as non-hemolytic. Antibacterial tests revealed significant reductions in Staphylococcus aureus and Pseudomonas aeruginosa survival, addressing infection concerns in chronic wounds. Furthermore, in vivo studies have demonstrated that the utilization of SF-Co-D/PVA-CS-CeNPs nanofibrous membrane as a dressing for full-thickness skin wounds in rats has resulted in accelerated tissue regeneration.
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Affiliation(s)
- Zoleikha Azari
- Bhbahan Faculty of Medical Sciences, Behbahan, Iran; Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Sadeghi-Avalshahr
- Department of Materials Research, Iranian Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi Branch, Mashhad, Iran; Tissue Engineering Research Group, Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Alipour
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Bahman Jalali Kondori
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vahid Reza Askari
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Mollazadeh
- Department of Materials Engineering, Faculty of Engineering, Ferdowsi University of Mashhad, Azadi Sq., Mashhad, Iran
| | - Simin Nazarnezhad
- Tissue Engineering Research Group, Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyedeh Najibeh Nasiri
- Tissue Engineering Research Group, Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farzad Kermani
- Tissue Engineering Research Group, Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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13
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Vlasova TI, Brodovskaya EP, Madonov KS, Ageev VP, Abelova AP, Pinyaev SI, Vlasov AP. Regenerative Potential of Platelet-Rich Plasma in Diabetes Mellitus. DOKLADY BIOLOGICAL SCIENCES : PROCEEDINGS OF THE ACADEMY OF SCIENCES OF THE USSR, BIOLOGICAL SCIENCES SECTIONS 2025; 521:123-133. [PMID: 40216681 DOI: 10.1134/s0012496624600556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 01/15/2025] [Accepted: 01/20/2025] [Indexed: 05/07/2025]
Abstract
The regenerative potential of platelet-rich plasma (PRP) samples from patients with type 1 diabetes mellitus (DM) was studied in vitro. In a series of experiments, PRP was added to the culture medium of human dermal fibroblasts. The cells were tested for metabolic (including reactive oxygen species production), migration, and proliferative activities at several time points; growth factors and exosome levels were assessed in PRP and the medium. A lower proliferative effect, pro-oxidant properties, and toxicity were observed for PRPs from diabetic patients. Namely, treated fibroblasts showed lower metabolic activity, a lower cell viability, and a greater percentage of necrosis in culture, while their migration properties were not impaired. PRPs from diabetic patients exerted a lower stimulatory effect on growth factor secretion by dermal fibroblasts. PRPs from elderly diabetics had the greatest effects.
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Affiliation(s)
- T I Vlasova
- Ogarev National Research Mordovian State University, Saransk, Russia.
| | - E P Brodovskaya
- Ogarev National Research Mordovian State University, Saransk, Russia
| | - K S Madonov
- Ogarev National Research Mordovian State University, Saransk, Russia
| | - V P Ageev
- Ogarev National Research Mordovian State University, Saransk, Russia
| | - A P Abelova
- Ogarev National Research Mordovian State University, Saransk, Russia
| | - S I Pinyaev
- Ogarev National Research Mordovian State University, Saransk, Russia
| | - A P Vlasov
- Ogarev National Research Mordovian State University, Saransk, Russia
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14
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Ghasemi Toudeshkchouei M, Abdoos H, Ai J, Nourbakhsh MS. Cellulose-based hydrogels enhanced with bioactive molecules for optimal chronic diabetic wound management. J Microencapsul 2025:1-24. [PMID: 40122056 DOI: 10.1080/02652048.2025.2480598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Accepted: 03/12/2025] [Indexed: 03/25/2025]
Abstract
Hydrogels are three-dimensional structures that replicate natural tissues' extracellular matrix (ECM). They are essential for transporting exudates, gases, and moisture and facilitating cellular interactions in tissue engineering and wound healing. The choice of primary material in designing the scaffold is necessary to be paid more attention rather than common sources, including plant fibres like cotton, bamboo, and algae, as well as bacterial and marine-derived materials. Among them, cellulose-based polymers are especially valued for their biocompatibility and ability to promote wound healing. Chronic diabetic wounds pose unique treatment challenges, such as necrosis and infection risks. Consequently, a growing interest is in incorporating bioactive molecules into cellulose-based hydrogels. This article investigates how these infused hydrogels enhance the healing process in chronic diabetic wounds, examining various loading and crosslinking techniques alongside their clinical applications. It also discusses the benefits and limitations of bioactive molecules and their interactions with hydrogels to improve treatment strategies.
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Affiliation(s)
| | - Hassan Abdoos
- Department of Nanotechnology, Faculty of New Sciences and Technologies, Semnan University, Semnan, Iran
| | - Jafar Ai
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - M S Nourbakhsh
- Faculty of Materials and Metallurgical Engineering, Semnan University, Semnan, Iran
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15
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Farooq M, Hwang M, Khan AW, Batool M, Ahmad B, Kim W, Kim MS, Choi S. Identification of a novel fibroblast growth factor receptor-agonistic peptide and its effect on diabetic wound healing. Life Sci 2025; 364:123432. [PMID: 39884341 DOI: 10.1016/j.lfs.2025.123432] [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: 12/03/2024] [Revised: 01/17/2025] [Accepted: 01/27/2025] [Indexed: 02/01/2025]
Abstract
AIMS Fibroblast growth factor (FGF) is a broad class of secretory chemicals that act via FGF receptors (FGFR). The study aims to explore the role of a novel peptide, FAP1 (FGFR-agonistic peptide 1), in tissue regeneration and repair. It investigates whether FAP1 mimics basic fibroblast growth factor (bFGF) and accelerates wound healing both in vitro and in vivo. MAIN METHODS In this study, a novel peptide was designed and its ability to mimic bFGF was assessed through different in vitro experiments including its effect on cell proliferation, wound healing, cell signaling including FGFR1 phosphorylation and activation of mitogen-activated protein kinases (MAPKs). Specificity was confirmed through surface plasmon resonance (SPR) analysis and co-treatment with FGFR inhibitor, erdafitinib. In vivo, the effect of FAP1 on diabetic wound healing was tested in a mouse model, examining collagen production and the migration and proliferation of keratinocytes and fibroblasts. KEY FINDINGS FAP1 specifically phosphorylated FGFR and activated MAPKs similar to bFGF. In vitro, it induced cell proliferation and accelerated wound healing. In vivo, FAP1 improved diabetic wound healing by increasing collagen production and promoting keratinocyte and fibroblast migration and proliferation. The specificity of FAP1 was confirmed through SPR. SIGNIFICANCE FAP1 shows potential as a novel pharmacological alternative to natural bFGF for skin tissue regeneration and repair. Its ability to accelerate wound healing and its specificity for FGFR suggest that FAP1 could serve as a cost-effective substitute for bFGF protein in therapeutic applications.
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Affiliation(s)
- Mariya Farooq
- S&K Therapeutics, Ajou University Campus Plaza 418, Worldcup-ro 199, Yeongton-gu, Suwon 16502, Republic of Korea; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea
| | - Moonjung Hwang
- Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea
| | - Abdul Waheed Khan
- Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea
| | - Maria Batool
- S&K Therapeutics, Ajou University Campus Plaza 418, Worldcup-ro 199, Yeongton-gu, Suwon 16502, Republic of Korea
| | - Bilal Ahmad
- S&K Therapeutics, Ajou University Campus Plaza 418, Worldcup-ro 199, Yeongton-gu, Suwon 16502, Republic of Korea
| | - Wook Kim
- Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea
| | - Moon Suk Kim
- Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.
| | - Sangdun Choi
- S&K Therapeutics, Ajou University Campus Plaza 418, Worldcup-ro 199, Yeongton-gu, Suwon 16502, Republic of Korea.
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16
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Arneth B, Abdelmonem R, El-Nabarawi MA, Teaima MH, Rashwan KO, Soliman MA, Al-Samadi IEI. Optimized Hesperidin-Loaded Lipid Nanoparticles with Tea Tree Oil for Enhanced Wound Healing: Formulation, Characterization, and Evaluation. Pharmaceuticals (Basel) 2025; 18:290. [PMID: 40143069 PMCID: PMC11946831 DOI: 10.3390/ph18030290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/10/2025] [Accepted: 02/16/2025] [Indexed: 03/28/2025] Open
Abstract
Objectives: This study aimed to develop hesperidin solid lipid nanoparticles (HESP-SLNs) to enhance their stability, solubility, and sustained release for wound healing; further enhancement was achieved through prepared nanostructured lipid carriers (HESP-NLCs) using Tea Tree Oil (TTO) to explore their synergistic efficacy. Methods: A factorial design of 24 trials was established to evaluate the influence of lipid type (X1), lipid conc (%) (X2), surfactant type (X3), and sonication amplitude (%) (X4) of prepared HESP-SLNs on the particle size (nm) (Y1), polydispersibility index (Y2), zeta potential (Y3), and encapsulation efficiency (%) (Y4). The optimized HESP-SLNs formula was selected utilizing Design Expert® software version 13, which was additionally enhanced by preparing TTO-loaded HESP-NLCs. In vitro release, Raman spectroscopy, and transmission electron microscopy were carried out for both lipid nanoparticles. Cytotoxicity, in vivo wound-healing assessments, and skin irritancy tests were performed to evaluate the performance of TTO-incorporated HESP-NLCs compared to HESP-SLNs. Results: The optimized formula demonstrated PS (280 ± 1.35 nm), ZP (-39.4 ± 0.92 mV), PDI (0.239 ± 0.012), and EE% (88.2 ± 2.09%). NLCs enhanced Q6% release, (95.14%) vs. (79.69%), for SLNs and showed superior antimicrobial efficacy. Both lipid nanoparticles exhibited spherical morphology and compatibility between HESP and excipients. NLCs achieved the highest wound closure percentage, supported by histological analysis and inflammatory biomarker outcomes. Cytotoxicity evaluation showed 87% cell viability compared to untreated HSF cells, and the skin irritancy test confirmed the safety of NLCs. Conclusions: TTO-loaded HESP-NLCs are promising candidates exhibiting superior wound-healing capabilities, making them a potential therapeutic option for cutaneous wound management.
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Affiliation(s)
- Borros Arneth
- Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University Marburg, 35043 Marburg, Germany
- Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Justus Liebig University Giessen, 35392 Giessen, Germany
| | - Rehab Abdelmonem
- Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza 12566, Egypt; (R.A.); (M.A.S.); (I.E.I.A.-S.)
| | - Mohamed A. El-Nabarawi
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Giza 11562, Egypt; (M.A.E.-N.)
| | - Mahmoud Hassan Teaima
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Giza 11562, Egypt; (M.A.E.-N.)
| | - Kareem Omar Rashwan
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt;
| | - Mohamed A. Soliman
- Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza 12566, Egypt; (R.A.); (M.A.S.); (I.E.I.A.-S.)
| | - Inas Essam Ibrahim Al-Samadi
- Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza 12566, Egypt; (R.A.); (M.A.S.); (I.E.I.A.-S.)
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Malueg MD, Baig AA, Moser M, Donnelly BM, Im J, Lim J, Okai BK, Housley SB, Siddiqui AH, Snyder KV. Preliminary Experience Using Axolotl (Ambystoma mexicanum) Dermis Patches as a Biologic Agent for Wound Management After Neurosurgical Procedures. World Neurosurg 2025; 194:123409. [PMID: 39522808 DOI: 10.1016/j.wneu.2024.10.138] [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: 08/14/2024] [Revised: 10/28/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVE In the United States, chronic wounds affect more than 6.5 million people annually-a mean cost of $23,755 among neurosurgery patients. Current wound management solutions have disadvantages, including rejection, disease transmission from mammalian sources, and cultural issues prohibiting some products. Here, we describe preliminary use of xenograft tissue derived from axolotl (Ambystoma mexicanum) dermis for use in wound management after neurosurgical procedures. METHODS Our prospective database was retrospectively searched for consecutive patients who underwent wound closures using axolotl dermis patches (NeoMatriX, NeXtGen Biologics, Alachua, FL). Patient demographics, daily alcohol and tobacco use, radiation history, operation type, and antibiotic regimens postclosure were collected. Rates of postoperative infection, wound dehiscence, and wound revision or repeated irrigation were collected for outcomes assessment. RESULTS Twenty-three patients underwent wound closure with the patches. At least 1 comorbidity related to delayed wound closure was present in included patients: obesity = 8 (34.8%), diabetes = 3 (13%), chronic obstructive pulmonary disease = 3 (13%), hypertension = 11 (47.8%), hyperlipidemia = 10 (43.5%), hypothyroidism = 3 (13%), benign prostatic hyperplasia = 3 (13%), human immunodeficiency virus = 1 (4.3%), cancer = 7 (30.4%), daily alcohol use = 4 (17.4%), and current smoking = 7 (30.4%). Wounds treated were from decompressive laminectomy, microvascular decompression, thoracolumbar instrumentation revision, and pseudoaneurysm ligation/resection in 1 (4.3%) patient each. Three (13%) patients had wounds from aneurysm clippings, 6 (26.1%) each from craniotomies and wound dehiscence treatments, and 4 (17.4%) from cranioplasties. Patches were applied for primary wound closure in 14 (60.9%) patients and secondary wound closure in 9 (39.1%) patients. Postapplication wound infection or wound dehiscence and/or revision occurred in 2 (8.7%) patients. CONCLUSIONS Axolotl dermis patches support mammalian wound management, demonstrating favorable potential in improving neurosurgical wound closure and healing and overall outcomes.
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Affiliation(s)
- Megan D Malueg
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Ammad A Baig
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Matthew Moser
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Brianna M Donnelly
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Justin Im
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Jaims Lim
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Bernard K Okai
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Steven B Housley
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA
| | - Adnan H Siddiqui
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA; Department of Radiology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA; Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York, USA; Jacobs Institute, Buffalo, New York, USA
| | - Kenneth V Snyder
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York, USA; Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York, USA; Jacobs Institute, Buffalo, New York, USA.
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18
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Dhanraj P, Boodhoo K, van de Vyver M. Delayed Immune Response Upon Injury in Diabetic Wounds Impedes Healing. Immun Inflamm Dis 2025; 13:e70142. [PMID: 39891428 PMCID: PMC11786017 DOI: 10.1002/iid3.70142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 01/13/2025] [Accepted: 01/19/2025] [Indexed: 02/03/2025] Open
Abstract
BACKGROUND Chronic wounds are a severe complication of diabetes. Dysregulated inflammatory signalling is thought to underly the poor healing outcomes. Yet, there is little information available on the acute response following injury and its impact on healing. METHODS Using a murine full thickness excisional wound model, the current study therefore assessed the expression of pro-inflammatory and pro-resolving lipid mediators during the early stages post injury in acute and diabetic wounds and compared the timeframe for transitioning through the phases of healing. Tissue eicosanoid (LTB4, PGE2, TxA2, MaR1, RvE1, RvD1, PD) and MMP-9 levels were assessed at 6 h post wounding using ELISAs. Wound closure, healing dynamics (histology), cellular infiltration and MPO, TNF-α expression (IHC) were assessed at 6 h, day2, day7 post wounding. RESULTS Eicosanoid expression did not differ between groups (LTB4 24-125 pg/mL, PGE2 63-177 pg/mL, TxA2 529-1184 pg/mL, MaR1 365-2052 pg/mL, RvE1 43-1157 pg/mL, RvD1 1.5-69 pg/mL, PD1 11.5-4.9 ng/mL). An inverse relationship (p < 0.05) between MMP-9 and eicosanoids were however only evident in acute and not in diabetic wounds. Diminished cellular infiltration (x5 fold) (p < 0.05) in diabetic wounds coincided with a significant delay in the expression of TNF-α (pro-inflammatory cytokine) and MPO (neutrophil marker). A significant difference in the expression of TNF-α (C 1.8 ± 0.6; DM 0.7 ± 0.1 MFI) and MPO (C 4.9 ± 1.9; DM 0.9 ± 0.4 MFI) (p < 0.05) was observed as early as 6 h post wounding, with histology parameters supporting the notion that the onset of the acute inflammatory response is delayed in diabetic wounds. CONCLUSION These observations imply that the immune cells are unresponsive to the initial eicosanoid expression in the diabetic wound tissue.
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Affiliation(s)
- Priyanka Dhanraj
- Experimental Medicine Research Group, Department of Medicine, Faculty of Medicine and Health SciencesStellenbosch UniversityCape TownWestern CapeSouth Africa
| | - Kiara Boodhoo
- Experimental Medicine Research Group, Department of Medicine, Faculty of Medicine and Health SciencesStellenbosch UniversityCape TownWestern CapeSouth Africa
| | - Mari van de Vyver
- Experimental Medicine Research Group, Department of Medicine, Faculty of Medicine and Health SciencesStellenbosch UniversityCape TownWestern CapeSouth Africa
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Bai Z, Zhou D, Tao K, Lin F, Wang H, Sun H, Liu R, Li Z. The Role of MicroRNA-206 in the Regulation of Diabetic Wound Healing via Hypoxia-Inducible Factor 1-Alpha. Biochem Genet 2025; 63:393-410. [PMID: 38446322 PMCID: PMC11832568 DOI: 10.1007/s10528-024-10759-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 02/25/2024] [Indexed: 03/07/2024]
Abstract
Successful wound healing in diabetic patients is hindered by dysregulated miRNA expression. This study aimed to investigate the abnormal expression of miRNAs in diabetic wound healing and the potential therapeutic role of modulating the miR-206/HIF-1α pathway. MicroRNA assays were used to identify differentially expressed miRNAs in diabetic wound sites and adjacent areas. In vitro models and a rat diabetic model were established to evaluate the effects of miR-206 on HIF-1α regulation and wound healing. The study revealed differential expression of miR-206 in diabetic wound tissues, its interaction with HIF-1α, and the inhibitory effect of miR-206 on cell growth under high glucose conditions. Modulating the miR-206/HIF-1α pathway using miR-206 antagomir promoted HIF-1α, CD34, and VEGF expression, ultimately enhancing diabetic wound healing.
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Affiliation(s)
- Zeming Bai
- Burn and Plastic Surgery Department, General Hospital of Northern Theater Command, Shenyang, 110000, China
| | - Dapeng Zhou
- Burn and Plastic Surgery Department, General Hospital of Northern Theater Command, Shenyang, 110000, China.
| | - Kai Tao
- Burn and Plastic Surgery Department, General Hospital of Northern Theater Command, Shenyang, 110000, China.
| | - Feng Lin
- Burn and Plastic Surgery Department, General Hospital of Northern Theater Command, Shenyang, 110000, China
| | - Hongyi Wang
- Burn and Plastic Surgery Department, General Hospital of Northern Theater Command, Shenyang, 110000, China
| | - Haiwei Sun
- Burn and Plastic Surgery Department, General Hospital of Northern Theater Command, Shenyang, 110000, China
| | - Ruidi Liu
- Burn and Plastic Surgery Department, General Hospital of Northern Theater Command, Shenyang, 110000, China
| | - Zhe Li
- Burn and Plastic Surgery Department, General Hospital of Northern Theater Command, Shenyang, 110000, China
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20
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Bramian A, Ling K, Butsenko D, Komatsu D, Wang E. Insulin dependence as an independent predictor of complications following surgical treatment of distal radius fracture. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY & TRAUMATOLOGY : ORTHOPEDIE TRAUMATOLOGIE 2025; 35:56. [PMID: 39841281 DOI: 10.1007/s00590-025-04173-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Accepted: 01/15/2025] [Indexed: 01/23/2025]
Abstract
PURPOSE Diabetes mellitus (DM) is a well-established risk factor for postoperative complications. Distal radius fractures (DRFs) are a common orthopedic injury and often require open reduction and internal fixation (ORIF). The rise of ORIF utilization warrants investigation into factors that may expose patients to postoperative complications following DRF ORIF. METHODS We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for cases of DRF ORIF between 2015 and 2021. Cases were stratified into cohorts based on diabetes mellitus (DM) status. The DM cohort was further stratified into non-insulin-dependent DM (NIDDM) and insulin-dependent DM (IDDM) groups. Bivariate logistic regression was performed to compare patient demographics, comorbidities, and 30-day postoperative complications. Multivariate logistic regressions were performed to identify associations between diabetes mellitus status and postoperative complications. RESULTS A total of 27,761 cases of DRF ORIF were identified from 2015 to 2021. After exclusion criteria were applied, 25,971 cases remained, of which 2169 (8.4%) cases had DM and 23,802 (91.6%) cases were free of DM. Within the DM cohort, there were 1392 cases in the NIDDM subgroup and 777 cases in the IDDM subgroup. Relative to the cohort without diabetes, the IDDM cohort was independently associated with sepsis, septic shock, reintubation, myocardial infarction, blood transfusion, failure to wean off mechanical ventilation, readmission, and nonhome discharge. CONCLUSION Having IDDM was independently associated with higher rates of postoperative sepsis, septic shock, reintubation, myocardial infarction, blood transfusion, failure to wean off ventilation, readmission, and nonhome discharge when compared to the cohort without diabetes following DRF ORIF. LEVEL OF EVIDENCE Level III; Retrospective cohort comparison; Prognosis study.
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Affiliation(s)
| | - Kenny Ling
- Stony Brook University Hospital, Stony Brook, USA
| | | | | | - Edward Wang
- Stony Brook University Hospital, Stony Brook, USA
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21
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Zhu Y, Shrestha A. Metabolic syndrome and its effect on immune cells in apical periodontitis- a narrative review. Clin Oral Investig 2025; 29:67. [PMID: 39825203 DOI: 10.1007/s00784-025-06161-3] [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: 11/07/2024] [Accepted: 01/11/2025] [Indexed: 01/20/2025]
Abstract
OBJECTIVES Apical periodontitis (AP) is an inflammatory immune response in periapical tissues caused by microbial infections. Failure of root canal treatment or delayed healing is often due to intracanal or extra-radicular bacteria. However, beyond microbial factors, the patient's systemic health can significantly influence the progression and healing of AP. Metabolic syndrome is a risk factor and it is characterized by a cluster of interconnected metabolic risk factors, including abdominal obesity, hyperlipidemia, hypertension, and hyperglycemia. MATERIALS AND METHODS A comprehensive literature review was conducted on apical periodontitis and metabolic syndrome, and their impact on the roles of different immune cell populations. RESULTS Both AP and metabolic syndrome are inflammatory diseases that involve complex and interwoven immune responses. The affected immune cells are categorized into the innate (neutrophils, macrophages, and dendritic cells) and adaptive immune systems (T cells and B cells). CONCLUSIONS Metabolic diseases and AP are closely correlated, possibly intertwined in a two-way relationship driven by a shared dysregulated immune response. CLINICAL RELEVANCE Understanding the pathophysiology and immune mechanisms underlying the two-way relationship between metabolic syndrome and AP can help improve treatment outcomes and enhance the overall well-being of patients with endodontic disease complicated by metabolic syndrome.
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Affiliation(s)
- Yi Zhu
- Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON, M5G 1G6, Canada
| | - Annie Shrestha
- Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON, M5G 1G6, Canada.
- Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
- Department of Dentistry, Mt. Sinai Hospital, Toronto 412-600 University Avenue, Toronto, ON, M5G 1X5, Canada.
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22
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Neuhoferova E, Kindermann M, Buzgo M, Vocetkova K, Panek D, Cigler P, Benson V. Topical siRNA therapy of diabetic-like wound healing. J Mater Chem B 2025; 13:1037-1051. [PMID: 39630486 DOI: 10.1039/d4tb01547a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Non-healing wounds are a serious complication in diabetic patients. One of the detrimental factors contributing to limited wound healing is the accumulation of metalloproteinase-9 (MMP-9) in the wound. Selective inhibition of MMP-9 is one of the established therapeutic targets for diabetic wound healing. Here, a functional and biocompatible wound dressing is developed to enable a controlled release of a traceable vector loaded with the antisense siRNA against MMP-9 in the wound. The dressing consists of degradable polymer nanofibers embedded with a vector nanosystem - polymer-coated fluorescent nanodiamonds optimized for the binding of siRNA and colloidal stability of nanodiamond-siRNA complexes in a physiological environment. The developed dressing is tested on murine fibroblasts and also applied to wounds in a diabetic murine model to evaluate its suitability in terms of in vivo toxicity, biological efficacy, and handling. The treatment results in significant local inhibition of MMP-9 and a shortening of the wound healing time. The scar formation in treated diabetic-like mice becomes comparable with that in non-treated diabetes-free mice. Our results suggest that the application of our biocompatible dressing loaded with a non-toxic vector nanosystem is an effective and promising approach to gene therapy of non-healing wounds.
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Affiliation(s)
- Eva Neuhoferova
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czechia.
- Faculty of Science, Charles University, Hlavova 2030, Prague 2, 128 40, Czechia
| | - Marek Kindermann
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 2, 166 10, Prague 6, Czechia.
- Department of Physical Chemistry, University of Chemistry and Technology Prague, Technicka 5, 166 28 Prague 6, Czechia
| | - Matej Buzgo
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague, Czechia
- InoCure s.r.o., Politickych veznu 13, 100 00, Prague, Czechia
| | - Karolina Vocetkova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague, Czechia
| | - Dalibor Panek
- Faculty of Biomedical Engineering, Czech Technical University in Prague, Namesti Sitna 3105, Kladno 2, 272 01, Czechia
| | - Petr Cigler
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo namesti 2, 166 10, Prague 6, Czechia.
| | - Veronika Benson
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czechia.
- Technical University of Liberec, Faculty of Health Studies, Trebizskeho 1402, 46001, Liberec, Czechia
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23
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Song J, Wu Y, Chen Y, Sun X, Zhang Z. Epigenetic regulatory mechanism of macrophage polarization in diabetic wound healing (Review). Mol Med Rep 2025; 31:2. [PMID: 39422035 PMCID: PMC11551531 DOI: 10.3892/mmr.2024.13367] [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: 07/27/2024] [Accepted: 09/24/2024] [Indexed: 10/19/2024] Open
Abstract
Diabetic wounds represent a significant complication of diabetes and present a substantial challenge to global public health. Macrophages are crucial effector cells that play a pivotal role in the pathogenesis of diabetic wounds, through their polarization into distinct functional phenotypes. The field of epigenetics has emerged as a rapidly advancing research area, as this phenomenon has the potential to markedly affect gene expression, cellular differentiation, tissue development and susceptibility to disease. Understanding epigenetic mechanisms is crucial to further exploring disease pathogenesis. A growing body of scientific evidence has highlighted the pivotal role of epigenetics in the regulation of macrophage phenotypes. Various epigenetic mechanisms, such as DNA methylation, histone modification and non‑coding RNAs, are involved in the modulation of macrophage phenotype differentiation in response to the various environmental stimuli present in diabetic wounds. The present review provided an overview of the various changes that take place in macrophage phenotypes and functions within diabetic wounds and discussed the emerging role of epigenetic modifications in terms of regulating macrophage plasticity in diabetic wounds. It is hoped that this synthesis of information will facilitate the elucidation of diabetic wound pathogenesis and the identification of potential therapeutic targets.
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Affiliation(s)
- Jielin Song
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
| | - Yuqing Wu
- The First Clinical Medical College, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, P.R. China
| | - Yunli Chen
- The First Clinical Medical College, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, P.R. China
| | - Xu Sun
- Department of Traditional Chinese Medicine Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
| | - Zhaohui Zhang
- Department of Traditional Chinese Medicine Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
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24
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Abavisani M, Hoseinzadeh M, Khayami R, Kodori M, Soleimanpour S, Sahebkar A. Statins, Allies against Antibiotic Resistance? Curr Med Chem 2025; 32:729-752. [PMID: 37644745 DOI: 10.2174/0929867331666230829141301] [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: 02/06/2023] [Revised: 06/22/2023] [Accepted: 07/20/2023] [Indexed: 08/31/2023]
Abstract
Due to the ever-increasing rate of antibacterial resistance, the search for effective antibacterial agents has become imperative. Researchers have investigated the potential antimicrobial properties of various classes of nonantibiotic drugs. Statins are a group of antihyperlipidemic drugs with several cholesterol-independent effects, including antiinflammatory, immune-modulating, antioxidant, and antibacterial effects. In vitro and in vivo studies have demonstrated the antibacterial properties of statins against various grampositive and gram-negative bacteria. Simvastatin and atorvastatin are the most potent members of the family. Their antibacterial effect can be attributed to several direct and indirect mechanisms. Bacterial invasion, growth, and virulence are affected by statins. However, since in vitro minimum inhibitory concentrations (MICs) are significantly higher than serum concentrations at the lipid-lowering dosage, indirect mechanisms have been suggested to explain the positive clinical results, including reducing inflammation and improving immune response capacity. Further, statins have shown promising results when combined with antibiotics and other antibacterial agents, such as triazenes and silver nanoparticles. Despite this, the controversial aspects of statins have cast doubt on their efficacy as a possible solution for antibacterial resistance, and further research is required. Consequently, this review will examine in detail the current clinical and in vitro findings and controversies regarding statins' antibacterial properties and their relevance to antibacterial resistance.
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Affiliation(s)
- Mohammad Abavisani
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Melika Hoseinzadeh
- Dental Research Center, Mashhad Dental School, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Khayami
- Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mansoor Kodori
- Non-communicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran
| | - Saman Soleimanpour
- Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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25
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Mgwenya TN, Abrahamse H, Houreld NN. Photobiomodulation studies on diabetic wound healing: An insight into the inflammatory pathway in diabetic wound healing. Wound Repair Regen 2025; 33:e13239. [PMID: 39610015 PMCID: PMC11628774 DOI: 10.1111/wrr.13239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 08/06/2024] [Accepted: 09/02/2024] [Indexed: 11/30/2024]
Abstract
Diabetes mellitus remains a global challenge to public health as it results in non-healing chronic ulcers of the lower limb. These wounds are challenging to heal, and despite the different treatments available to improve healing, there is still a high rate of failure and relapse, often necessitating amputation. Chronic diabetic ulcers do not follow an orderly progression through the wound healing process and are associated with a persistent inflammatory state characterised by the accumulation of pro-inflammatory macrophages, cytokines and proteases. Photobiomodulation has been successfully utilised in diabetic wound healing and involves illuminating wounds at specific wavelengths using predominantly light-emitting diodes or lasers. Photobiomodulation induces wound healing through diminishing inflammation and oxidative stress, among others. Research into the application of photobiomodulation for wound healing is current and ongoing and has drawn the attention of many researchers in the healthcare sector. This review focuses on the inflammatory pathway in diabetic wound healing and the influence photobiomodulation has on this pathway using different wavelengths.
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Affiliation(s)
- Tintswalo N. Mgwenya
- Laser Research Centre, Faculty of Health SciencesUniversity of JohannesburgJohannesburgGautengSouth Africa
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health SciencesUniversity of JohannesburgJohannesburgGautengSouth Africa
| | - Nicolette N. Houreld
- Laser Research Centre, Faculty of Health SciencesUniversity of JohannesburgJohannesburgGautengSouth Africa
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26
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Wang J, Zhang CN, Xu X, Sun TC, Kong LC, Ning RD. In Situ Formation of Hydrogels Loaded with ZnO Nanoparticles Promotes Healing of Diabetic Wounds in Rats. ACS OMEGA 2024; 9:51442-51452. [PMID: 39758615 PMCID: PMC11696414 DOI: 10.1021/acsomega.4c08537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/01/2024] [Accepted: 12/09/2024] [Indexed: 01/07/2025]
Abstract
The challenge of healing diabetic skin wounds presents a significant hurdle in clinical practice and scientific research. In response to this pressing concern, we have developed a temperature-sensitive, in situ-forming hydrogel comprising poly(n-isopropylacrylamide166-co-n-butyl acrylate9) -poly(ethylene glycol) -poly(n-isopropylacrylamide166-co-butyl acrylate9) copolymer, denoted as PEP, in combination with zinc oxide nanoparticles, forming what we refer to as PEP-ZnO hydrogel. The antimicrobial properties of the PEP-ZnO hydrogel against methicillin-resistant Staphylococcus aureus were rigorously assessed by using the bacteriostatic banding method. In vitro evaluations encompassed examinations of hemocompatibility and biocompatibility. The study further employed a diabetic Sprague-Dawley (SD) rat whole-layer trauma model for comprehensive in vivo analyses. In vivo healing assessments revealed the potential of the PEP-ZnO hydrogel, characterized by increased collagen deposition and enhanced vascularization at the trauma site, thus significantly expediting the healing process. Collectively, these findings endorse the PEP-ZnO hydrogel as a safe and effective dressing for addressing chronic wounds in diabetic patients. This hydrogel not only holds promise for improving the quality of life for diabetic individuals grappling with chronic wounds but also represents a noteworthy advancement in wound care.
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Affiliation(s)
- Jun Wang
- The
Third Affiliated Hospital of Anhui Medical University, The First People’s
Hospital of Hefei, Anhui, Hefei 230000, China
| | - Cheng-Nan Zhang
- The
Third Affiliated Hospital of Anhui Medical University, The First People’s
Hospital of Hefei, Anhui, Hefei 230000, China
| | - Xun Xu
- The
Third Affiliated Hospital of Anhui Medical University, The First People’s
Hospital of Hefei, Anhui, Hefei 230000, China
| | - Tian-Ci Sun
- Hefei
University of Technology, Anhui, Hefei 230000, China
| | - Ling-Chao Kong
- The
Third Affiliated Hospital of Anhui Medical University, The First People’s
Hospital of Hefei, Anhui, Hefei 230000, China
| | - Ren-De Ning
- The
Third Affiliated Hospital of Anhui Medical University, The First People’s
Hospital of Hefei, Anhui, Hefei 230000, China
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27
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Murray PE, Coffman JA, Garcia-Godoy F. Oral Pathogens' Substantial Burden on Cancer, Cardiovascular Diseases, Alzheimer's, Diabetes, and Other Systemic Diseases: A Public Health Crisis-A Comprehensive Review. Pathogens 2024; 13:1084. [PMID: 39770344 PMCID: PMC11677847 DOI: 10.3390/pathogens13121084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 11/28/2024] [Accepted: 12/06/2024] [Indexed: 01/11/2025] Open
Abstract
This review synthesizes the findings from 252 studies to explore the relationship between the oral pathogens associated with periodontitis, dental caries, and systemic diseases. Individuals with oral diseases, such as periodontitis, are between 1.7 and 7.5 times (average 3.3 times) more likely to develop systemic diseases or suffer adverse pregnancy outcomes, underscoring the critical connection between dental and overall health. Oral conditions such as periodontitis and dental caries represent a significant health burden, affecting 26-47% of Americans. The most important oral pathogens, ranked by publication frequency, include the herpes virus, C. albicans, S. mutans, P. gingivalis, F. nucleatum, A. actinomycetemcomitans, P. intermedia, T. denticola, and T. forsythia. The systemic diseases and disorders linked to oral infections, ranked similarly, include cancer, respiratory, liver, bowel, fever, kidney, complications in pregnancy, cardiovascular bacteremia, diabetes, arthritis, autoimmune, bladder, dementia, lupus, and Alzheimer's diseases. Evidence supports the efficacy of dental and periodontal treatments in eliminating oral infections and reducing the severity of systemic diseases. The substantial burden that oral pathogens have on cancer, cardiovascular diseases, Alzheimer's, diabetes, and other systemic diseases poses a significant public health crisis.
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Affiliation(s)
| | - Jonathan A Coffman
- College of Pharmacy, American University of Health Sciences, Signal Hill, CA 90755, USA
| | - Franklin Garcia-Godoy
- College of Dentistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA
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28
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Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 2024; 7:43716. [PMID: 39990247 PMCID: PMC11844764 DOI: 10.33137/cpoj.v7i2.43716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 11/29/2024] [Indexed: 02/25/2025] Open
Abstract
BACKGROUND The timely provision of load-bearing prostheses significantly reduces healthcare costs and lowers post-amputation mortality risk. However, current methods for assessing residuum health remain subjective, underscoring the need for standardized, evidence-based approaches incorporating physical biomarkers to evaluate residual limb healing and determine readiness for prosthetic rehabilitation. OBJECTIVES This review aimed to identify predictive, diagnostic, and indicative physical biomarkers of healing of the tissues and structures found in the residual limbs of adults with amputation. METHODOLOGY A scoping review was conducted following Joanna Briggs Institute (JBI) and PRISMA-ScR guidance. Searches using "biomarkers", "wound healing", and "amputation" were performed on May 6, 2023, on Web of Science, Ovid MEDLINE, Ovid Embase, Scopus, Cochrane, PubMed, and CINAHL databases. Inclusion criteria were: 1) References to physical biomarkers and healing; 2) Residuum tissue healing; 3) Clear methodology with ethical approval; 4) Published from 2017 onwards. Articles were assessed for quality (QualSyst tool) and evidence level (JBI system), and categorized by study, wound, and model type. Physical biomarkers that were repeated not just within categories, but across more than one of the study categories were reported on. FINDINGS The search strategy identified 3,306 sources, 157 of which met the inclusion criteria. Histology was the most frequently repeated physical biomarker used in 64 sources, offering crucial diagnostic insights into cellular healing processes. Additional repeated indicative and predictive physical biomarkers, including ankle-brachial index, oxygenation measures, perfusion, and blood pulse and pressure measurements, were reported in 25, 19, 13, and 12 sources, respectively, providing valuable data on tissue oxygenation and vascular health. CONCLUSION Ultimately, adopting a multifaceted approach that integrates a diverse array of physical biomarkers (accounting for physiological factors and comorbidities known to influence healing) may substantially enhance our understanding of the healing process and inform the development of effective rehabilitation strategies for individuals undergoing amputation.
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Affiliation(s)
- H Williams-Reid
- Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, Scotland
| | | | - A Buis
- Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, Scotland
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29
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Salama A, Elsherbiny N, Hetta HF, Safwat MA, Atif HM, Fathalla D, Almanzalawi WS, Almowallad S, Soliman GM. Curcumin-loaded gold nanoparticles with enhanced antibacterial efficacy and wound healing properties in diabetic rats. Int J Pharm 2024; 666:124761. [PMID: 39332460 DOI: 10.1016/j.ijpharm.2024.124761] [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: 05/20/2024] [Revised: 09/23/2024] [Accepted: 09/24/2024] [Indexed: 09/29/2024]
Abstract
Diabetic wounds pose a significant global health challenge. Although curcumin exhibits promising wound healing and antibacterial properties, its clinical potential is limited by low aqueous solubility, and poor tissue penetration. This study aimed to address these challenges and enhance the wound healing efficacy of curcumin by loading it onto gold nanoparticles (AuNPs). The properties of the AuNPs, including particle size, polydispersity index (PDI), zeta potential, percent drug entrapment efficiency (%EE) and UV-Vis spectra were significantly influenced by the curcumin/gold chloride molar ratio used in the synthesis of AuNPs. The optimal formulation (F2) exhibited the smallest particle size (41.77 ± 6.8 nm), reasonable PDI (0.59 ± 0.17), high %EE (94.43 ± 0.25 %), a moderate zeta potential (-8.44 ± 1.69 mV), and a well-defined surface Plasmon resonance peak at 526 nm. Formulation F2 was incorporated into Pluronic® F127 gel to facilitate its application to the skin. Both curcumin AuNPs solution and gel showed sustained drug release and higher skin permeation parameters compared with the free drug solution. AuNPs significantly enhanced curcumin's antibacterial efficacy by lowering the minimum inhibitory concentrations and enhancing antibacterial biofilm activity against various Gram-positive and Gram-negative bacterial strains. In a diabetic wound rat model, AuNPs-loaded curcumin exhibited superior wound healing attributes compared to the free drug. Specifically, it demonstrated improved wound healing percentage, reduced wound oxidative stress, increased wound collagen deposition, heightened anti-inflammatory effects, and enhanced angiogenesis. These findings underscore the potential of AuNPs as efficacious delivery systems of curcumin for improved wound healing applications.
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Affiliation(s)
- Ayman Salama
- Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Nehal Elsherbiny
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Helal F Hetta
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Mohamed A Safwat
- Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt
| | - Huda M Atif
- Department of Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Egypt
| | - Dina Fathalla
- Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | - Wejdan S Almanzalawi
- PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Sanaa Almowallad
- Department of Biochemistry, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Ghareb M Soliman
- Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia.
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30
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Swathi K, Sumathi S, Somit K, Shubashini SK. Reverse pharmacology approach to validate the diabetic wound-healing activity of Jatyadi thailam formulations in vitro on diabetic mimic environment. Arch Physiol Biochem 2024; 130:710-723. [PMID: 37897224 DOI: 10.1080/13813455.2023.2264536] [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: 07/04/2023] [Revised: 08/30/2023] [Accepted: 09/22/2023] [Indexed: 10/29/2023]
Abstract
OBJECTIVE Jatyadi thailam, an Ayurvedic preparation, is renowned for its efficacy in diabetic wound healing and inflammation. This study aimed to validate and compare the diabetic wound-healing potential of two Jatyadi thailam formulations - Ayurvedic formulary of India Jatyadi thailam (JT-AFI) and Yogagrantha formulation of Jatyadi thailam (JT-YG), in a diabetic environment using L929 fibroblast cells in vitro. METHODOLOGY The effects on cell survival, proliferation, migration, angiogenesis, cell cycle progression, apoptosis, ROS generation, and mitochondrial function were evaluated. RESULTS The formulations promoted cell proliferation, migration, angiogenesis, while also regulating cell cycle and apoptosis. They effectively suppressed ROS generation and modulated mitochondrial function. JT-AFI exhibited superior efficacy in accelerating diabetic wound healing compared to JT-YG. CONCLUSION These findings provide substantial support for the mechanistic role of Jatyadi thailam in diabetic wound healing.
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Affiliation(s)
- Kandasamy Swathi
- Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, India
| | - Sundaravadivelu Sumathi
- Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, India
| | | | - Sripathi K Shubashini
- Department of Chemistry, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, India
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31
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Liu Y, Zhou M, Sun J, Yao E, Xu J, Yang G, Wu X, Xu L, Du J, Jiang X. Programmed BRD9 Degradation and Hedgehog Signaling Activation via Silk-Based Core-Shell Microneedles Promote Diabetic Wound Healing. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2404130. [PMID: 39413023 PMCID: PMC11615742 DOI: 10.1002/advs.202404130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 08/06/2024] [Indexed: 10/18/2024]
Abstract
Wound healing impairment in diabetes mellitus is associated with an excessive inflammatory response and defective regeneration capability with suppressed Hedgehog (Hh) signaling. The bromodomain protein BRD9, a subunit of the non-canonical BAF chromatin-remodeling complex, is critical for macrophage inflammatory response. However, whether the epigenetic drug BRD9 degrader can attenuate the sustained inflammatory state of wounds in diabetes remains unclear. Without a bona fide immune microenvironment, Hh signaling activation fails to effectively rescue the suppressed proliferative ability of dermal fibroblasts and the vascularization of endothelial cells. Therefore, a silk-based core-shell microneedle (MN) patch is proposed to dynamically modulate the wound immune microenvironment and the regeneration process. Specifically, the BRD9 degrader released from the shell of the MNs mitigated the excessive inflammatory response in the early phase. Subsequently, the positively charged Hh signaling agonist is released from the negatively charged core of the silk fibroin nanofibers and promotes the phase transition from inflammation to regeneration, including re-epithelialization, collagen deposition, and angiogenesis. These findings suggest that the programmed silk-based core-shell MN patch is an ideal therapeutic strategy for effective skin regeneration in diabetic wounds.
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Affiliation(s)
- Yili Liu
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
| | - Mingliang Zhou
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
| | - Jinrui Sun
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
| | - Enhui Yao
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
| | - Jingyi Xu
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
| | - Guangzheng Yang
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
| | - Xiaolin Wu
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
| | - Ling Xu
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
| | - Jiahui Du
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
| | - Xinquan Jiang
- Department of ProsthodonticsShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200125China
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Sharma Y, Ghatak S, Sen CK, Mohanty S. Emerging technologies in regenerative medicine: The future of wound care and therapy. J Mol Med (Berl) 2024; 102:1425-1450. [PMID: 39358606 DOI: 10.1007/s00109-024-02493-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 09/10/2024] [Accepted: 09/23/2024] [Indexed: 10/04/2024]
Abstract
Wound healing, an intricate biological process, comprises orderly phases of simple biological processed including hemostasis, inflammation, angiogenesis, cell proliferation, and ECM remodeling. The regulation of the shift in these phases can be influenced by systemic or environmental conditions. Any untimely transitions between these phases can lead to chronic wounds and scarring, imposing a significant socio-economic burden on patients. Current treatment modalities are largely supportive in nature and primarily involve the prevention of infection and controlling inflammation. This often results in delayed healing and wound complications. Recent strides in regenerative medicine and tissue engineering offer innovative and patient-specific solutions. Mesenchymal stem cells (MSCs) and their secretome have gained specific prominence in this regard. Additionally, technologies like tissue nano-transfection enable in situ gene editing, a need-specific approach without the requirement of complex laboratory procedures. Innovating approaches like 3D bioprinting and ECM bioscaffolds also hold the potential to address wounds at the molecular and cellular levels. These regenerative approaches target common healing obstacles, such as hyper-inflammation thereby promoting self-recovery through crucial signaling pathway stimulation. The rationale of this review is to examine the benefits and limitations of both current and emerging technologies in wound care and to offer insights into potential advancements in the field. The shift towards such patient-centric therapies reflects a paradigmatic change in wound care strategies.
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Affiliation(s)
- Yashvi Sharma
- Stem Cell Facility (DBT-Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Subhadip Ghatak
- Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
- McGowan Institute of Regenerative Medicine, Department of Surgery, University of Pittsburgh, 419 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA, 15219, USA
| | - Chandan K Sen
- Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
- McGowan Institute of Regenerative Medicine, Department of Surgery, University of Pittsburgh, 419 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
| | - Sujata Mohanty
- Stem Cell Facility (DBT-Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India.
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Mahendran MIMS, Gopalakrishnan V, Saravanan V, Dhamodharan R, Jothimani P, Balasubramanian M, Singh AK, Vaithianathan R. Managing drug therapy-related problems and assessment of chronic diabetic wounds. Curr Med Res Opin 2024; 40:2077-2093. [PMID: 39402701 DOI: 10.1080/03007995.2024.2414893] [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: 05/25/2024] [Revised: 09/12/2024] [Accepted: 10/07/2024] [Indexed: 11/02/2024]
Abstract
Type 2 diabetes mellitus (T2DM), responsible for most diabetes cases recorded worldwide, increases the risk of chronic wounds and amputation. Patients with T2DM appear to be more susceptible to delayed wound healing due to their treatment adherence. This review explores the specifics of polypharmacy, side effects, possible drug interactions and the importance of medication adherence for therapeutic efficacy. We discuss the effects of anti-diabetes medications on wound healing as well as the role that biofilms and microbial infections play in diabetic wounds. Inconsistent use of medications can lead to poor glycaemic control, which negatively affects the healing process of diabetic foot ulcers. Managing chronic wounds represents a substantial portion of healthcare expenditures. Biofilm-associated infections are difficult for the immune system to treat and respond inconsistently to antibiotics as these infections are slow growing and persistent. Additionally, we emphasize the critical role pharmacists play in enhancing patient adherence and optimizing diabetes treatment by offering comprehensive coverage of drugs associated with problems related to pharmacological therapy in type 2 diabetes.
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Affiliation(s)
| | - Vinoj Gopalakrishnan
- MGM Advanced Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Pondicherry, India
| | - Vaijayanthi Saravanan
- MGM Advanced Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Pondicherry, India
| | - Ramasamy Dhamodharan
- MGM Advanced Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Pondicherry, India
| | - Pradeep Jothimani
- MGM Advanced Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Pondicherry, India
| | - M Balasubramanian
- MGM Advanced Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Pondicherry, India
| | - Abhimanyu Kumar Singh
- MGM Advanced Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Pondicherry, India
| | - Rajan Vaithianathan
- Department of Surgery, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Pondicherry, India
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Kostova M, Alexander TD, De La Cruz Monroy M, Murdeshwar H, Duvnjak H, McCance HC, Natalwala I, Rahman S, Fredericks-Bowyer LJ. The Efficacy of Biodegradable Temporising Matrix for Upper Limb Reconstruction: A Systematic Review and Meta-Analysis. Cureus 2024; 16:e75994. [PMID: 39711936 PMCID: PMC11661895 DOI: 10.7759/cureus.75994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 12/24/2024] Open
Abstract
The objective of this systematic review and meta-analysis is to assess the efficacy of the biodegradable temporising matrix (BTM) (NovoSorb; PolyNovo Biomaterials Pty Ltd, Port Melbourne, Victoria, Australia) in the reconstruction of complex upper extremity wounds. The authors conducted a systematic review and meta-analysis as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines assessing the efficacy of BTM in complex upper extremity wound reconstruction. The primary outcome measures were successful BTM integration and the proportion of wounds healed. Secondary outcomes analysed were the average time from BTM application to its integration, the proportion of wounds healed by secondary intention, graft take over BTM, as well as the incidence of infection. The rate of complications as well as scarring and outcomes in upper limb function were also evaluated. The inclusion criteria were met by 12 studies consisting of 164 complex upper extremity wounds. Successful BTM integration was reported in 92.1% (p<0.001) of cases, coupled with wound healing achieved in 90% (p<0.001) of cases overall. The average time to integration for BTM was 37.37 days (p<0.001). The average infection rate for upper extremity wounds with BTM application was 8.5% (p<0.001). Satisfactory scarring and functional outcomes were reported in the majority of the studies. The authors conclude that BTM offers good wound healing outcomes for upper extremity reconstruction. The studies analysed indicate good graft take rates and a low infection incidence; however, further prospective randomised studies are required to support the efficacy of BTM compared to other dermal matrices.
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Affiliation(s)
- Mariana Kostova
- Otolaryngology, Leeds Teaching Hospitals NHS Trust, Leeds, GBR
| | - Thomas D Alexander
- Otolaryngology, Warrington and Halton Teaching Hospitals NHS Foundation Trust, Warrington, GBR
| | | | | | - Haris Duvnjak
- Otolaryngology, Wrexham Maelor Hospital, Wrexham, GBR
| | | | | | - Shafiq Rahman
- Plastic Surgery, Northern General Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, GBR
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Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 1 - A scoping review of healing and non-healing definitions. CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 2024; 7:43715. [PMID: 39990241 PMCID: PMC11844765 DOI: 10.33137/cpoj.v7i2.43715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 10/25/2024] [Indexed: 02/25/2025] Open
Abstract
BACKGROUND Following lower limb amputation, timely prosthetic fitting enhances mobility and quality of life. However, inconsistent definitions of surgical site healing complicate prosthesis readiness assessment and highlight the need for objective wound management measures. OBJECTIVE This review aimed to compile definitions of healing and non-healing provided in the literature investigating biomarkers of healing of the tissues and structures found in the residual limbs of adults with amputation. METHODOLOGY A scoping review was conducted following JBI and PRISMA-ScR guidance. Searches using "biomarkers," "wound healing," and "amputation" were performed on May 6, 2023, on Web of Science, Ovid MEDLINE, Ovid Embase, Scopus, Cochrane, PubMed, and CINAHL databases. Inclusion criteria were: 1) References to biomarkers and healing; 2) Residuum tissue healing; 3) Clear methodology with ethical approval; 4) Published from 2017 onwards. Articles were assessed for quality (QualSyst tool) and evidence level (JBI system). FINDINGS Of 3,306 articles screened, 219 met the inclusion criteria and are reviewed in this article, with 77% rated strong quality. 43% of all included sources did not define healing, while the remainder used specific criteria including epithelialization (14%), wound size reduction (28%), gradings scales (3%), scarring (1%), absence of wound complications (2%), hydroxyproline levels (0.5%), no amputation (0.5%), or neovascularization (0.5%). 84% of included sources did not provide definitions of non-healing. Studies defining non-healing used criteria like wound complications (4%), the need for operative interventions (4%), or lack of wound size reduction (1%). For 10% of included sources, healing and non-healing definitions were considered not applicable given the research content. Total percentages exceed 100% for both healing and non-healing definitions because some sources used two definition classifications, such as epithelialization and wound size reduction. The findings indicate a lack of standardized definitions irrespective of study type. CONCLUSION This review reveals significant gaps in current definitions of healing and non-healing, often based on superficial assessments that overlook deeper tissue healing and mechanical properties essential for prosthesis use. It emphasizes the need for comprehensive definitions incorporating biomarkers and psychosocial factors to improve wound management and post-amputation recovery.
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Affiliation(s)
- H Williams-Reid
- Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, Scotland
| | | | - A Buis
- Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, Scotland
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Khattak S, Ullah I, Sohail M, Akbar MU, Rauf MA, Ullah S, Shen J, Xu H. Endogenous/exogenous stimuli‐responsive smart hydrogels for diabetic wound healing. AGGREGATE 2024. [DOI: 10.1002/agt2.688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
AbstractDiabetes significantly impairs the body's wound‐healing capabilities, leading to chronic, infection‐prone wounds. These wounds are characterized by hyperglycemia, inflammation, hypoxia, variable pH levels, increased matrix metalloproteinase activity, oxidative stress, and bacterial colonization. These complex conditions complicate effective wound management, prompting the development of advanced diabetic wound care strategies that exploit specific wound characteristics such as acidic pH, high glucose levels, and oxidative stress to trigger controlled drug release, thereby enhancing the therapeutic effects of the dressings. Among the solutions, hydrogels emerge as promising due to their stimuli‐responsive nature, making them highly effective for managing these wounds. The latest advancements in mono/multi‐stimuli‐responsive smart hydrogels showcase their superiority and potential as healthcare materials, as highlighted by relevant case studies. However, traditional wound dressings fall short of meeting the nuanced needs of these wounds, such as adjustable adhesion, easy removal, real‐time wound status monitoring, and dynamic drug release adjustment according to the wound's specific conditions. Responsive hydrogels represent a significant leap forward as advanced dressings proficient in sensing and responding to the wound environment, offering a more targeted approach to diabetic wound treatment. This review highlights recent advancements in smart hydrogels for wound dressing, monitoring, and drug delivery, emphasizing their role in improving diabetic wound healing. It addresses ongoing challenges and future directions, aiming to guide their clinical adoption.
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Affiliation(s)
- Saadullah Khattak
- The Fifth Affiliated Hospital of Wenzhou Medical University Lishui China
| | - Ihsan Ullah
- Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou Institute University of Chinese Academy of Sciences Wenzhou China
| | - Mohammad Sohail
- The Fifth Affiliated Hospital of Wenzhou Medical University Lishui China
| | - Muhammad Usman Akbar
- Oujiang Laboratory Key Laboratory of Alzheimer's Disease of Zhejiang Province Institute of Aging Wenzhou Medical University Wenzhou China
| | - Mohd Ahmar Rauf
- Department of Internal Medicine, Heme Oncology Unit, University of Michigan Ann Arbor Michigan USA
| | - Salim Ullah
- The Fifth Affiliated Hospital of Wenzhou Medical University Lishui China
| | - Jianliang Shen
- National Engineering Research Center of Ophthalmology and Optometry Eye Hospital Wenzhou Medical University Wenzhou China
- Wenzhou Institute University of Chinese Academy of Sciences Wenzhou China
| | - Hong‐Tao Xu
- The Fifth Affiliated Hospital of Wenzhou Medical University Lishui China
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Woo K, Santamaria N, Beeckman D, Alves P, Cullen B, Gefen A, Lázaro-Martínez JL, Lev-Tov H, Najafi B, Sharpe A, Swanson T. Using patient-reported experiences to inform the use of foam dressings for hard-to-heal wounds: perspectives from a wound care expert panel. J Wound Care 2024; 33:814-822. [PMID: 39480734 DOI: 10.12968/jowc.2024.0027] [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] [Indexed: 11/02/2024]
Abstract
Caring for patients with hard-to-heal (chronic) wounds requires a multifaceted approach that addresses their diverse needs, which can contribute to the complexity of care. Wound care providers must have a comprehensive understanding of the patient's comorbid conditions and psychosocial issues to provide personalised and effective treatment. Key quality indicators for effective wound care involves not only selecting appropriate local wound care products, such as foam dressings, but also addressing individual patient experiences of wound-related pain, odour, itch, excessive wound drainage, and self-care needs. The purpose of this review is to inculcate the wound care practice community, research scientists and healthcare industry with a sense of accountability in order to work collaboratively in addressing these unmet care needs.
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Affiliation(s)
- Kevin Woo
- 92 Barrie Street School of Nursing, Queen's University, Kingston, Ontario, Canada
- Toronto Grace Health Center, Toronto, Canada
| | - Nick Santamaria
- School of Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
| | - Dimitri Beeckman
- Skin Integrity Research Group (SKINT), University Centre for Nursing and Midwifery, Department of Public Health and Primary Care, Ghent University, Ghent, Belgium
- Campus UZGent, Gent, Belgium
| | - Paulo Alves
- Wounds Research Lab - Centre for Interdisciplinary Research in Health, Catholic University of Portugal, Porto, Portugal
| | | | - Amit Gefen
- Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel
| | - José Luis Lázaro-Martínez
- Director of the Diabetic Foot Research Group, Complutense University and Health Research Institute at San Carlos Teaching Hospital, Madrid, Spain
| | - Hadar Lev-Tov
- University of Miami Hospital Miller School of Medicine, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami, Florida, US
| | - Bijan Najafi
- Interdisciplinary Consortium on Advanced Motion Performance (iCAMP), Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston TX, US
| | - Andrew Sharpe
- Podiatry Department, Salford Royal NHS Foundation Trust, Salford Care Organisation, Salford, UK
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Patel VN, Patel HV, Agrawal K, Soni I, Shah P, Mangrulkar SV, Umekar MJ, Lalan MS. Comprehensive developmental investigation on simvastatin enriched bioactive film forming spray using the quality by design paradigm: a prospective strategy for improved wound healing. J Drug Target 2024; 32:1139-1153. [PMID: 39042496 DOI: 10.1080/1061186x.2024.2382405] [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: 05/07/2024] [Revised: 06/23/2024] [Accepted: 07/15/2024] [Indexed: 07/25/2024]
Abstract
The use of topical antimicrobials in wound healing presents challenges like risk of drug resistance and toxicity to local tissue. Simvastatin (SIM), a lipid-lowering agent which reduces the risk of cardiovascular events, is repurposed for its pleiotropic effect in wound healing. A bioactive bioadhesive polymer-based film forming spray (FFS) formulation of SIM was designed using chitosan, collagen, hyaluronic acid and optimised by employing the DoE approach. Optimised formulation demonstrated moderate viscosity (12.5 ± 0.3 cP), rapid film formation (231 ± 5.6 s), flexibility, tensile strength and sustained drug release (T80 - time for 80% drug release - 9.05 ± 0.7 h). Scanning electron microscopy (SEM) verified uniformly dispersed drug within the composite polymer matrix. SIM FFS demonstrated antimicrobial activity against gram positive and gram negative bacteria. In vivo excision wound model studies in mice affirmed the beneficent role of bioactive polymers and the efficacy of SIM FFS in wound contraction and closure, tissue remodelling and re-epithelization in comparison to standard antimicrobial preparation. Cytokines TNF- alpha, IL-6 were downregulated and IL-10 was upregulated. Biochemical markers; hydroxyproline, hexosamine and histopathology were consistent with wound contraction observed. This is an exploratory effort in repurposing SIM for wound healing in a novel dosage form, underscoring its potential as an alternative to conventional topical antimicrobials.
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Affiliation(s)
| | - Heta V Patel
- Babaria Institute of Pharmacy, BITS Edu Campus, Vadodara, India
| | - Kashish Agrawal
- Babaria Institute of Pharmacy, BITS Edu Campus, Vadodara, India
| | - Ishika Soni
- Babaria Institute of Pharmacy, BITS Edu Campus, Vadodara, India
| | - Pranav Shah
- Maliba Pharmacy College, Uka Tarsadia University, Surat, India
| | | | | | - Manisha S Lalan
- Parul Institute of Pharmacy & Research, Parul University, Vadodara, India
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Mgwenya TN, Abrahamse H, Houreld NN. Modulatory Effects of 830 nm on Diabetic Wounded Fibroblast Cells: An In Vitro Study on Inflammatory Cytokines. Photobiomodul Photomed Laser Surg 2024; 42:676-692. [PMID: 39253808 DOI: 10.1089/photob.2024.0041] [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] [Indexed: 09/11/2024] Open
Abstract
Background:After skin damage, a complicated set of processes occur for epidermal and dermal wound healing. This process is hindered under diabetic conditions, resulting in nonhealing diabetic ulcers. In diabetes there is an increase in inflammation and proinflammatory cytokines. Modulating cells using photobiomodulation (PBM) may have an effect on inflammation and cell viability, which are crucial for the healing of wounds. Objective: This study explored the impact of PBM in the near-infrared spectrum (830 nm; 5 J/cm2) on inflammation in diabetic wound healing. Materials and Methods: Five cell models, namely normal, wounded, diabetic, diabetic wounded, and wounded with d-galactose were used. Cell morphology and migration rate were assessed, while cellular response measures included viability (Trypan blue and adenosine triphosphate), apoptosis (annexin-V/PI), proinflammatory cytokines interleukin-6, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2, nuclear translocation of nuclear factor kappa B (NF-κB), and gene expression of advanced glycation end product receptor (AGER). Results: PBM resulted in increased levels of TNF-α, supported by activation of NF-κB. PBM stimulated translocation of NF-κB and upregulation of AGER. Conclusions: PBM modulates diabetic wound healing in vitro at 830 nm through stimulated NF-κB signaling activated by TNF-α.
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Affiliation(s)
- Tintswalo Nomsa Mgwenya
- Laser Research Center, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
| | - Heidi Abrahamse
- Laser Research Center, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
| | - Nicolette Nadene Houreld
- Laser Research Center, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
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Sarkar S, Mandal D, Ghosh A, Chattopadhyay D. Biopolymers in Wound Dressing. ACS SYMPOSIUM SERIES 2024:207-234. [DOI: 10.1021/bk-2024-1487.ch009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Affiliation(s)
- Sresha Sarkar
- Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Kolkata -700 009, India
| | - Debashmita Mandal
- Center for Research in Nanoscience and Nanotechnology, Acharya Prafulla Chandra Roy Sikhsha Prangan, University of Calcutta, JD-2, Sector-III, Salt Lake City, Kolkata-700098, India
| | - Adrija Ghosh
- Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Kolkata -700 009, India
| | - Dipankar Chattopadhyay
- Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Kolkata -700 009, India
- Center for Research in Nanoscience and Nanotechnology, Acharya Prafulla Chandra Roy Sikhsha Prangan, University of Calcutta, JD-2, Sector-III, Salt Lake City, Kolkata-700098, India
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da Silva JGM, de Melo IMF, Alves ÉR, de Oliveira GM, da Silva AA, Pinto FCM, Aguiar JLDA, Araújo DN, Teixeira VW, Teixeira ÁAC. Melatonin associated with bacterial cellulose-based hydrogel improves healing of skin wounds in diabetic rats. Acta Cir Bras 2024; 39:e399024. [PMID: 39476070 PMCID: PMC11506694 DOI: 10.1590/acb399024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 09/21/2024] [Indexed: 11/02/2024] Open
Abstract
PURPOSE To describe the effects of melatonin associated with bacterial cellulose-based hydrogel on healing of skin wounds in diabetic rats. METHODS Streptozotocin was used to induce diabetes in Wistar rats. After wound induction, animals were randomly divided into groups GC, GDCC, GDCB, and GDMCB. Animals were evaluated in days 3, 7, and 14 for the following variables: glycemic levels, histopathological and histochemical analyses, healing rate, morphometry and C-reactive protein. RESULTS There was no change in glycemic levels in the diabetic animals as a result of the treatments; histopathological analyses showed better healing in GDCB and GDMCB groups, as well as histochemistry; at day 14, the highest healing rate was observed in animals from the GDMCB group, reaching almost 100%; morphometry revealed a significant increase of fibroblasts and reduction of macrophages and blood vessels in lesions treated with bacterial cellulose associated or not with melatonin when compared to the other experimental groups. There was also an increase in C-reactive protein in GDCC group at day 14. CONCLUSION Bacterial cellulose-based dressings associated with systemic melatonin showed beneficial results in experimentally induced wounds in diabetic rats, favoring the healing process.
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Affiliation(s)
- Jaiurte Gomes Martins da Silva
- Universidade Federal Rural de Pernambuco – Department of Animal Morphology and Physiology – Graduate Program in Animal Bioscience – Recife (PE) – Brazil
- Universidade Federal de Alagoas – Maceió (AL) – Brazil
| | - Ismaela Maria Ferreira de Melo
- Universidade Federal Rural de Pernambuco – Department of Animal Morphology and Physiology – Graduate Program in Animal Bioscience – Recife (PE) – Brazil
| | - Érique Ricardo Alves
- Universidade Federal Rural de Pernambuco – Department of Animal Morphology and Physiology – Graduate Program in Animal Bioscience – Recife (PE) – Brazil
| | - Glícia Maria de Oliveira
- Universidade Federal de Pernambuco – Department of Biochemistry – Graduate Program in Therapeutic Innovation – Recife (PE) – Brazil
| | - Anderson Arnaldo da Silva
- Universidade Federal de Pernambuco – Graduate Program in Biosciences and Biotechnology in Health – Recife (PE) – Brazil
| | | | | | | | - Valéria Wanderley Teixeira
- Universidade Federal Rural de Pernambuco – Department of Animal Morphology and Physiology – Graduate Program in Animal Bioscience – Recife (PE) – Brazil
| | - Álvaro Aguiar Coelho Teixeira
- Universidade Federal Rural de Pernambuco – Department of Animal Morphology and Physiology – Graduate Program in Animal Bioscience – Recife (PE) – Brazil
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Dhiman M, Ghosh S, Singh TG, Chauhan S, Roy P, Lahiri D. Exploring the potential of an Aloe vera and honey extract loaded bi-layered nanofibrous scaffold of PCL-Col and PCL-SBMA mimicking the skin architecture for the treatment of diabetic wounds. J Mater Chem B 2024; 12:10383-10408. [PMID: 39290135 DOI: 10.1039/d4tb01469c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Diabetic wounds are often chronic in nature, and issues like elevated blood sugar, bacterial infections, oxidative stress and persistent inflammation impede the healing process. To ensure the appropriate healing of wounds, scaffolds should promote complete tissue regeneration in wounds, both functionally and structurally. However, the available scaffolds lack the explicit architecture and functionality that could match those of native skin, thus failing to carry out the scar-free skin regeneration in diabetic wounds. This study deals with the synthesis of a bi-layered nanofibrous scaffold mimicking the native skin architecture in terms of porosity and hydrophobic-hydrophilic gradients. In addition, herbal extracts of Aloe vera and litchi honey were added in consecutive layers to manage the high blood glucose level, inflammation, and increased ROS level associated with diabetic wounds. In vitro studies confirmed that the prepared scaffold with herbal extracts showed enhanced proliferation of skin cells with good mechanical strength, degradability, anti-bacterial and anti-diabetic properties. The scaffold also demonstrated superior wound healing in vivo with quicker scar-free wound recovery and appropriate skin regeneration, compared to conventional treatment. Altogether, the synthesized herbal extract loaded bi-layered nanofibrous scaffold can be used as a regenerative template for hard-to-heal diabetic wounds, offering a new strategy for the management of chronic wounds.
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Affiliation(s)
- Megha Dhiman
- Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
- Biomaterials and Multiscale Mechanics Laboratory, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
| | - Souvik Ghosh
- Molecular Endocrinology Laboratory, Department of Bioscience and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
- Biomaterials and Multiscale Mechanics Laboratory, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
| | | | - Samrat Chauhan
- Chitkara College of Pharmacy, Chikara University Rajpura, Punjab 140401, India
| | - Partha Roy
- Molecular Endocrinology Laboratory, Department of Bioscience and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
| | - Debrupa Lahiri
- Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
- Biomaterials and Multiscale Mechanics Laboratory, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
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Nasra S, Pramanik S, Oza V, Kansara K, Kumar A. Advancements in wound management: integrating nanotechnology and smart materials for enhanced therapeutic interventions. DISCOVER NANO 2024; 19:159. [PMID: 39354172 PMCID: PMC11445205 DOI: 10.1186/s11671-024-04116-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 09/23/2024] [Indexed: 10/03/2024]
Abstract
Wound management spans various techniques and materials tailored to address acute and chronic non-healing wounds, with the primary objective of achieving successful wound closure. Chronic wounds pose additional challenges, often necessitating dressings to prepare the wound bed for subsequent surgical procedures like skin grafting. Ideal dressing materials should not only expedite wound healing but also mitigate protein, electrolyte, and fluid loss while minimizing pain and infection risk. Nanotechnology has emerged as a transformative tool in wound care, revolutionizing the landscape of biomedical dressings. Its application offers remarkable efficacy in accelerating wound healing and combating bacterial infections, representing a significant advancement in wound care practices. Integration of nanotechnology into dressings has resulted in enhanced properties, including improved mechanical strength and controlled drug release, facilitating tailored therapeutic interventions. This review article comprehensively explores recent breakthroughs in wound healing therapies, with a focus on innovative medical dressings such as nano-enzymes. Additionally, the utilization of smart materials, like hydrogels and electroactive polymers, in wound dressings offers dynamic functionalities to promote tissue regeneration. Emerging concepts such as bio-fabrication, microfluidic systems, bio-responsive scaffolds, and personalized therapeutics show promise in expediting wound healing and minimizing scarring. Through an in-depth exploration of these advancements, this review aims to catalyze a paradigm shift in wound care strategies, promoting a patient-centric approach to therapeutic interventions.
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Affiliation(s)
- Simran Nasra
- Biological and Life Sciences, School of Arts a Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, Gujarat, 380009, India
| | - Sanjali Pramanik
- Biological and Life Sciences, School of Arts a Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, Gujarat, 380009, India
| | - Vidhi Oza
- Biological and Life Sciences, School of Arts a Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, Gujarat, 380009, India
| | - Krupa Kansara
- Biological Engineering Discipline, Indian Institute of Technology Gandhinagar, Palaj, Gujarat, 382355, India.
| | - Ashutosh Kumar
- Biological and Life Sciences, School of Arts a Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, Gujarat, 380009, India.
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Bashiri Z, Sharifi AM, Ghafari M, Hosseini SJ, Shahmahmoodi Z, Moeinzadeh A, Parsaei H, Khadivi F, Afzali A, Koruji M. In-vitro and in-vivo evaluation of angiogenic potential of a novel lithium chloride loaded silk fibroin / alginate 3D porous scaffold with antibacterial activity, for promoting diabetic wound healing. Int J Biol Macromol 2024; 277:134362. [PMID: 39089552 DOI: 10.1016/j.ijbiomac.2024.134362] [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: 04/05/2024] [Revised: 07/01/2024] [Accepted: 07/29/2024] [Indexed: 08/04/2024]
Abstract
Healing diabetic ulcers with chronic inflammation is a major challenge for researchers and professionals, necessitating new strategies. To rapidly treat diabetic wounds in rat models, we have fabricated a composite scaffold composed of alginate (Alg) and silk fibroin (SF) as a wound dressing that is laden with molecules of lithium chloride (LC). The physicochemical, bioactivity, and biocompatibility properties of Alg-SF-LC scaffolds were investigated in contrast to those of Alg, SF, and Alg-SF ones. Afterward, full-thickness wounds were ulcerated in diabetic rats in order to evaluate the capacity of LC-laden scaffolds to regenerate skin. The characterization findings demonstrated that the composite scaffolds possessed favorable antibacterial properties, cell compatibility, high swelling, controlled degradability, and good uniformity in the interconnected pore microstructure. Additionally, in terms of wound contraction, re-epithelialization, and angiogenesis improvement, LC-laden scaffolds revealed better performance in diabetic wound healing than the other groups. This research indicates that utilizing lithium chloride molecules loaded in biological materials supports the best diabetic ulcer regeneration in vivo, and produces a skin replacement with a cellular structure comparable to native skin.
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Affiliation(s)
- Zahra Bashiri
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Omid Fertility & Infertility Clinic, Hamedan, Iran.
| | - Ali Mohammad Sharifi
- Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran; Tissue Engineering Group (NOCERAL), Department of Orthopedics Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
| | - Mozhdeh Ghafari
- Department of Chemistry, Isfahan University of Technology, Isfahan, Iran
| | - Seyed Jamal Hosseini
- Biomedical Engineering Department, Amirkabir University of Technology, Tehran, Iran; Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Zeinab Shahmahmoodi
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.; Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Alaa Moeinzadeh
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.; Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Houman Parsaei
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Farnaz Khadivi
- Department of Anatomy, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Azita Afzali
- Hajar hospital, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Morteza Koruji
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Sangalli L, Banday F, Sullivan A, Anjum K. Systemic Factors Affecting Prognosis and Outcomes in Periodontal Disease. Dent Clin North Am 2024; 68:571-602. [PMID: 39244245 DOI: 10.1016/j.cden.2024.05.001] [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] [Indexed: 09/09/2024]
Abstract
This review delves into the effects of autoimmune conditions like rheumatoid arthritis, inflammatory disorders such as irritable bowel syndrome, cardiovascular disease, diabetes, infectious ailments like human immunodeficiency virus, and their medications on periodontal therapy outcomes. It also explores the influence of hormones. Understanding these systemic factors is crucial for optimizing periodontal health and treatment efficacy. The review underscores the necessity of considering these variables in periodontal care. Other vital systemic factors are addressed elsewhere in this special edition.
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Affiliation(s)
- Linda Sangalli
- College of Dental Medicine, Midwestern University, 555 31st, Downers Grove, IL, USA
| | - Fatma Banday
- Rutgers School of Dental Medicine, 110 Bergen Street, Newark, NJ, USA
| | - Andrew Sullivan
- Rutgers School of Dental Medicine, 110 Bergen Street, Newark, NJ, USA
| | - Kainat Anjum
- Rutgers School of Dental Medicine, 110 Bergen Street, Newark, NJ, USA.
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Kaussikaa S, Prasad MK, Ramkumar KM. Nrf2 Activation in Keratinocytes: A Central Role in Diabetes-Associated Wound Healing. Exp Dermatol 2024; 33:e15189. [PMID: 39373525 DOI: 10.1111/exd.15189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 08/28/2024] [Accepted: 09/21/2024] [Indexed: 10/08/2024]
Abstract
Wound healing is a complex biological process crucial for tissue repair, wherein keratinocytes play a pivotal role in initiating, sustaining and completing the cascade. Various local and systemic factors, such as lifestyle, age metabolic disorders and vascular insufficiency, can influence this process, and in the context of diabetic wounds, disrupted biological mechanisms, including inflammation, tissue hypoxia, decrease in collagen production along with increased oxidative stress and keratinocyte dysfunction, contribute to delayed healing. During re-epithelialisation, keratinocytes undergo rapid multiplication and migration, forming a dense hyperproliferative epithelial layer that restores the epidermal barrier. Nuclear factor-erythroid 2-related factor (Nrf2), a vital transcription factor, emerges as a central regulator in managing antioxidant proteins and detoxifying enzymes, serving as a guardian against elevated reactive oxygen species (ROS) levels during stress. Nrf2 also orchestrates angiogenesis and anti-inflammatory responses crucial for wound repair. Studies demonstrate that under high-glucose conditions, Nrf2 activation promotes wound healing by enhancing cell proliferation and migration while reducing apoptosis. Nrf2 activators stimulate endogenous antioxidant production, thereby mitigating oxidative stress. Furthermore, Nrf2 upregulation is associated with decreased expression of cytokines such as TNF-α and IL- 6. Recent research underscores the potential of bioactive molecules, including dietary polyphenols, traditional medicinal compounds and pharmacological agents, in activating Nrf2 and preventing diseases such as diabetes due to their robust antioxidative properties. This review aims to investigate the activation of Nrf2 by these bioactive molecules in cultured keratinocytes and animal models, elucidating the key molecular regulatory mechanisms involved in alleviating oxidative stress and facilitating the diabetic wound healing process. Understanding these complex pathways may offer insights into novel therapeutic strategies for enhanced wound healing in diabetes-associated complications.
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Affiliation(s)
- Srinivasan Kaussikaa
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Murali Krishna Prasad
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Kunka Mohanram Ramkumar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
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Zhu X, Zhang C, Jiang W, Zeng Z, Zhang K, Du M, Chen J, Wu Q, Liao W, Chen Y, Fang W, Pan W. Trem2 acts as a non-classical receptor of interleukin-4 to promote diabetic wound healing. Clin Transl Med 2024; 14:e70026. [PMID: 39350473 PMCID: PMC11442487 DOI: 10.1002/ctm2.70026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 05/28/2024] [Accepted: 05/31/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND The immunoglobulin superfamily protein Trem2 (triggering receptor expressed on myeloid cells 2) is primarily expressed on myeloid cells where it functions to regulate macrophage-related immune response induction. While macrophages are essential mediators of diabetic wound healing, the specific regulatory role that Trem2 plays in this setting remains to be established. OBJECTIVE This study was developed to explore the potential importance of Trem2 signalling in diabetic wound healing and to clarify the underlying mechanisms through which it functions. METHODS AND RESULTS Following wound induction, diabetic model mice exhibited pronounced upregulation of Trem2 expression, which was primarily evident in macrophages. No cutaneous defects were evident in mice bearing a macrophage-specific knockout of Trem2 (T2-cKO), but they induced more pronounced inflammatory responses and failed to effectively repair cutaneous wounds, with lower levels of neovascularization, slower rates of wound closure, decreased collagen deposition following wounding. Mechanistically, we showed that interleukin (IL)-4 binds directly to Trem2, inactivating MAPK/AP-1 signalling to suppress the expression of inflammatory and chemoattractant factors. Co-culture of fibroblasts and macrophages showed that macrophages from T2-cKO mice suppressed the in vitro activation and proliferation of dermal fibroblasts through upregulation of leukaemia inhibitory factor (Lif). Injecting soluble Trem2 in vivo was also sufficient to significantly curtail inflammatory responses and to promote diabetic wound healing. CONCLUSIONS These analyses offer novel insight into the role of IL-4/Trem2 signalling as a mediator of myeloid cell-fibroblast crosstalk that may represent a viable therapeutic target for efforts to enhance diabetic wound healing.
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Affiliation(s)
- Xinlin Zhu
- Department of DermatologyShanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE)Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Chao Zhang
- Department of DermatologyShanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE)Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Weiwei Jiang
- Department of DermatologyShanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE)Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Zhaoxiang Zeng
- Department of Vascular SurgeryShanghai General Hospital, School of MedicineShanghai Jiaotong UniversityShanghaiChina
| | - Keming Zhang
- Department of DermatologyShanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE)Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Mingwei Du
- Department of DermatologyShanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE)Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Juan Chen
- Department of DermatologyShanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE)Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Qian Wu
- Department of Laboratory MedicineTongren HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Wanqing Liao
- Department of DermatologyShanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE)Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Youming Chen
- Department of Infectious Diseases and ImmunologyShanghai Public Health Clinical CenterFudan UniversityShanghaiChina
| | - Wenjie Fang
- Department of DermatologyShanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE)Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Weihua Pan
- Department of DermatologyShanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE)Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina
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Hajj J, Sizemore B, Singh K. Impact of Epigenetics, Diet, and Nutrition-Related Pathologies on Wound Healing. Int J Mol Sci 2024; 25:10474. [PMID: 39408801 PMCID: PMC11476922 DOI: 10.3390/ijms251910474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 09/20/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Chronic wounds pose a significant challenge to healthcare. Stemming from impaired wound healing, the consequences can be severe, ranging from amputation to mortality. This comprehensive review explores the multifaceted impact of chronic wounds in medicine and the roles that diet and nutritional pathologies play in the wound-healing process. It has been well established that an adequate diet is crucial to proper wound healing. Nutrients such as vitamin D, zinc, and amino acids play significant roles in cellular regeneration, immune functioning, and collagen synthesis and processing. Additionally, this review discusses how patients with chronic conditions like diabetes, obesity, and nutritional deficiencies result in the formation of chronic wounds. By integrating current research findings, this review highlights the significant impact of the genetic make-up of an individual on the risk of developing chronic wounds and the necessity for adequate personalized dietary interventions. Addressing the nutritional needs of individuals, especially those with chronic conditions, is essential for improving wound outcomes and overall patient care. With new developments in the field of genomics, there are unprecedented opportunities to develop targeted interventions that can precisely address the unique metabolic needs of individuals suffering from chronic wounds, thereby enhancing treatment effectiveness and patient outcomes.
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Affiliation(s)
- John Hajj
- Indiana Center for Regenerative Medicine and Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (J.H.); (B.S.)
| | - Brandon Sizemore
- Indiana Center for Regenerative Medicine and Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (J.H.); (B.S.)
| | - Kanhaiya Singh
- Indiana Center for Regenerative Medicine and Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (J.H.); (B.S.)
- McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA
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Anbar HS, Shehab NG, Yasin A, Shaar LM, Ashraf R, Rahi Z, Alamir R, Alsabbagh D, Thabet A, Altaas I, Lozon YA, El Rouby NMM, Shahiwala A. The wound healing and hypoglycemic activates of date palm (Phoenix dactylifera) leaf extract and saponins in diabetic and normal rats. PLoS One 2024; 19:e0308879. [PMID: 39312526 PMCID: PMC11419346 DOI: 10.1371/journal.pone.0308879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 07/28/2024] [Indexed: 09/25/2024] Open
Abstract
INTRODUCTION Indigenous plants have historically been crucial in treating human diseases across various cultures worldwide. Research continues to uncover new therapeutic uses for indigenous plants, from treating infectious diseases to managing chronic conditions such as diabetes and wound care. This study aimed to examine the effect of palm tree leaves "Phoenix dactylifera L" extract and its topical film formulation on wound healing and blood glucose levels. METHODS Palm leaves were collected, authenticated, powdered, and extracted with ethanol by cold maceration. Saponins were isolated. The dried extract was analyzed using reverse-phase high-pressure liquid chromatography to identify the phytochemicals present. Diabetes mellitus was induced by a single intraperitoneal injection of Streptozotocin (40mg/kg). Rats with blood glucose levels ≥ 200 mg/dl were used to determine the reduction in blood glucose with or without the oral extract. Incision and excision wounds were induced in both diabetic and normal rats. Topical films containing extract or saponin and inert films were applied to the wounds every other day, and wound sizes were recorded until the wound was completely healed. RESULTS The presence of six flavonoids, Naringin, Rutin, Quercetin, Kaempferol, Apigenin, and Catechin, and five phenolic acids, Syringic acid, p Coumaric acid, Caffeic acid, Ferulic acid, Ellagic acid were detected in the dried extract. A significant reduction in blood sugar in diabetic rats and wound diameter in the treated group compared to the control group in both diabetic and normal rats was observed, confirming the promising role of palm leaf extract on diabetes and wound care. Macroscopic, morphometric, and histological data suggested that the cutaneous wound healing in rats treated with the leaf extract was better and faster than the control or inert groups. CONCLUSIONS Our research findings highlight the marked effect of Phoenix dactylifera extract as a supportive or alternative treatment for both hyperglycemia and incision or excision wounds. Further research and clinical trials are warranted to validate these findings and explore the underlying mechanisms of action.
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Affiliation(s)
- Hanan S. Anbar
- Department of Pharmaceutical Sciences, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Naglaa Gamil Shehab
- Department of Pharmaceutical Sciences, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
- Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Ayah Yasin
- Undergraduate Student, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Lana Mazen Shaar
- Undergraduate Student, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Ruba Ashraf
- Undergraduate Student, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Zahraa Rahi
- Undergraduate Student, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Raneem Alamir
- Undergraduate Student, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Deema Alsabbagh
- Undergraduate Student, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Aya Thabet
- Undergraduate Student, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Israa Altaas
- Undergraduate Student, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Yosra A. Lozon
- Department of Pharmaceutical Sciences, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Nadia M. M. El Rouby
- Department of Biomedical Sciences, Dubai Medical College for Girls, Dubai, United Arab Emirates
| | - Aliasgar Shahiwala
- Department of Pharmaceutical Sciences, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
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OuYang H, Yang J, Wan H, Huang J, Yin Y. Effects of different treatment measures on the efficacy of diabetic foot ulcers: a network meta-analysis. Front Endocrinol (Lausanne) 2024; 15:1452192. [PMID: 39377075 PMCID: PMC11456420 DOI: 10.3389/fendo.2024.1452192] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 08/29/2024] [Indexed: 10/09/2024] Open
Abstract
Introduction Through a network meta-analysis, we compared different treatment measures for patients with diabetic foot ulcers (DFU), assessing their impact on the healing of DFU and ranking them accordingly. Methods We searched the PubMed, the China National Knowledge Infrastructure (CNKI), Embase, the WanFang and the WeiPu database. The retrieval time was from database establishment to January 2024, and retrieval entailed subject and free words. Randomized controlled trials (RCTs) with different treatment measures for DFU were included. Data extraction and evaluation were based on the PRISMA guidelines. Meta-analyses using pairwise and network methods were employed to compare and rank the effectiveness of different treatments for DFU. Results Ultimately, we included 57 RCTs involving a total of 4,826 patients with DFU. When it comes to ulcer healing rates, compared to standard of care(SOC),platelet-rich plasma(PRP), hyperbaric oxygen therapy(HBOT), topical oxygen therapy(TOT), acellular dermal matrix(ADM), and stem cells(SCs) in both direct meta-analysis(DMA) and network meta-analysis(NMA) can effectively increase the complete healing rate. For Scs+PRP, a statistically significant improvement was only observed in the NMA. Moreover, when compared to the negative pressure wound therapy(NPWT) group, the PRP+NPWT group was more effective in promoting the complete healing of ulcers. In terms of promoting the reduction of ulcer area, no statistical differences were observed among various treatment measures. When it comes to ulcer healing time, both PRP and NPWT can effectively shorten the healing time compared to SOC. Furthermore, when compared to the NPWT group, the combined treatment of PRP and ultrasonic debridement(UD) with NPWT is more effective in reducing healing time. In terms of amputation rates and adverse reactions, the PRP group effectively reduced the amputation rate and adverse reactions for patients with DFU. Additionally, compared to the NPWT group, the combined treatment of PRP and UD with NPWT reduced the incidence of adverse reactions. However, no significant differences were observed among other treatment measures in terms of amputation rates and adverse reactions. The ranking results showed that the efficacy of PRP+NPWT and UD+NPWT in promoting ulcer healing, reducing ulcer area, shortening healing time, decreasing amputation rates and adverse reactions is superior to that of the alone PRP group, NPWT group, and UD group. Conversely, the SOC group demonstrates the least effective performance in all aspects. Conclusion Due to the particularity of the wound of DFU, the standard of care is not effective, but the new treatment scheme has a remarkable effect in many aspects. And the treatment of DFU is not a single choice, combined with a variety of methods often achieve better efficacy, and will not bring more adverse reactions.
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Affiliation(s)
- Hong OuYang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital(The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Jing Yang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital(The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Haiyan Wan
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital(The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Jiali Huang
- Geriatric Diseases Institute of Chengdu, Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital(The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China
| | - Yifan Yin
- Department of Nephrology, Chengdu Third People’s hospital, Chengdu, China
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