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Chu W, Sun X, Yan Y. Study on the regulation of renal tubular cell apoptosis by SIRT1/NF-κB signaling pathway in septic acute kidney injury. Ren Fail 2025; 47:2499904. [PMID: 40329161 PMCID: PMC12057794 DOI: 10.1080/0886022x.2025.2499904] [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: 10/10/2024] [Revised: 03/18/2025] [Accepted: 04/03/2025] [Indexed: 05/08/2025] Open
Abstract
SIRT1 regulates gene transcription via various signaling pathways, mitigating oxidative stress damage in renal tubular epithelial cells, reducing renal inflammation, and decreasing apoptosis in tubular cells. This study explores the mechanisms of action of SIRT1 in sepsis-induced acute kidney injury (AKI), offering a theoretical foundation for future treatments. Experiments were carried out in a CLP mouse model and an in vitro model using LPS-stimulated HK-2 cells. Immunoblotting and ELISA were employed to assess the expression levels of inflammatory cytokines (p < 0.01), finding that SIRT1 effectively reduces the inflammatory response in sepsis-induced AKI. Moreover, the detection of cell apoptosis via multiple pathways showed that SIRT1 can reduce the rate of cell apoptosis and effectively decrease oxidative stress in the validation reaction. Transmission electron microscopy observations further supported these findings, demonstrating that SIRT1 expression induces the blockade of cell apoptosis processes. The biochemical experiments concluded that SIRT1 ameliorates sepsis-induced AKI. Consequently, SIRT1 may represent a novel therapeutic target for AKI.
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Affiliation(s)
- Weiwei Chu
- Cadre Health Center, Shaoxing People’s Hospital, Shaoxing, China
| | - Xuedong Sun
- Intensive Care Unit, Shaoxing People’s Hospital, Shaoxing, China
| | - Yihe Yan
- Intensive Care Unit, Shaoxing People’s Hospital, Shaoxing, China
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2
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Zheng K, Raza F, Xiao W, Zafar H, Song H, Zhang F, Ge Z. Near-infrared light triggered bio-inspired enhanced natural silk fibroin nanofiber composite scaffold for photothermal therapy of periodontitis. Colloids Surf B Biointerfaces 2025; 251:114607. [PMID: 40073626 DOI: 10.1016/j.colsurfb.2025.114607] [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: 11/12/2024] [Revised: 02/27/2025] [Accepted: 03/02/2025] [Indexed: 03/14/2025]
Abstract
Periodontitis is one of the major oral health issues worldwide, with significant impacts on oral health and patients's quality of life, but current therapies have not achieved optimal regeneration of periodontal tissue. This study developed scaffolds using natural tussah silk fibroin (TSF) cross-linked with regenerated silk fibroin (SF) nanofibers to improve mechanical properties and wet-state stability. Zinc oxide (ZnO) and polydopamine (PDA) composite nanoparticles were loaded into scaffold to impart its antibacterial and photothermal properties to construct a photo-responsive composite scaffold (ZnO/PDA/TSF-SF). After characterization, ZnO/PDA/TSF-SF demonstrated excellent antibacterial ability, biocompatibility, and photothermal stability. In vitro cell evaluations under 635 nm red light irradiation-mediated photo-biomodulation (PBM) demonstrated that ZnO/PDA/TSF-SF promoted fibroblast proliferation and enhanced expression of proteins and genes associated with tissue repair, such as collagen I (Col I), fibronectin (FN), and alpha smooth muscle actin (α-SMA). A rat model of periodontitis developed for evaluations of antibacterial and tissue repair effects showed that ZnO/PDA/TSF-SF improved alveolar bone and reversed bone loss. ZnO/PDA/TSF-SF improved inflammation significantly through reduction in tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 levels in serum and gingival tissues of modeled rats. Also, the scaffold markedly increased levels of anti-inflammatory cytokine interleukin-10 (IL-10) and elevated protein and mRNA expression levels of tissue repair-related proteins and endothelial cell markers. ZnO/PDA/TSF-SF scaffold exhibited good biocompatibility, osteogenesis, and photo-responsive antibacterial properties, thereby demonstrating therapeutic potential in treating periodontitis.
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Affiliation(s)
- Kai Zheng
- Department of stomatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China
| | - Faisal Raza
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Wanshu Xiao
- Department of stomatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China
| | - Hajra Zafar
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Haiyao Song
- Department of stomatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China
| | - Feng Zhang
- College of Textile and Clothing Engineering, Soochow University, National Engineering Laboratory for Modern Silk, Suzhou, Jiangsu 215004, China; Jiangsu Engineering Research Center of Textile Dyeing and Printing for Energy Conservation, Discharge Reduction and Cleaner Production (ERC), Soochow University, Suzhou 215123, China.
| | - Zili Ge
- Department of stomatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.
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Jacobo-Delgado YM, Trujillo-Paez V, Santos-Mena A, Felix-Arellano C, Gonzalez-Curiel I, De Jesus-González LA, Rivas-Santiago B. Repurposing of activating transcription factor 3 (ATF3) activator molecules with potential wound-healing effects. Injury 2025; 56:112314. [PMID: 40220516 DOI: 10.1016/j.injury.2025.112314] [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: 02/04/2025] [Revised: 03/20/2025] [Accepted: 03/31/2025] [Indexed: 04/14/2025]
Abstract
BACKGROUND Wound healing is a complex and regulated process that involves the coordinated action of key signaling pathways. Activating transcription factor 3 (ATF3) is a stress-inducible protein that has recently emerged as a critical modulator of cellular responses to injury, including those involved in wound healing. AIM The aim of this study was to explore the repurposing of existing pharmacological agents to activate ATF3 and evaluate their potential to enhance wound healing factors. METHODS We selected three compounds: retin-A, furosemide, and acrivastine based on their ability to modulate ATF3 expression and assessed their effects on wound healing processes in primary cell cultures. We evaluated wound healing-related genes such as LL-37, HBD-2, HBD-3, and VEGFA by qPCR, and a wound healing scratch assay using keratinocytes was conducted to evaluate cell migration. RESULTS Interestingly, retin-A induced the expression of key wound healing-related genes, including HBD-2, HBD-3, LL-37, and VEGF. Also, retin-A was the only compound showing wound healing effects, while furosemide and acrivastine did not exhibit any noticeable activity. CONCLUSION Our research highlights the potential of retin-A as therapeutic agents to improve wound healing, particularly in chronic wound models.
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Affiliation(s)
- Yolanda M Jacobo-Delgado
- Zacatecas Biomedical Research Unit, Mexican Social Security Institute. Interior de la Alameda #45 Colonia Centro ZIP code 98000, Zacatecas, Mexico
| | - Valentin Trujillo-Paez
- Zacatecas Biomedical Research Unit, Mexican Social Security Institute. Interior de la Alameda #45 Colonia Centro ZIP code 98000, Zacatecas, Mexico
| | - Alan Santos-Mena
- Zacatecas Biomedical Research Unit, Mexican Social Security Institute. Interior de la Alameda #45 Colonia Centro ZIP code 98000, Zacatecas, Mexico
| | - Camelia Felix-Arellano
- Zacatecas Biomedical Research Unit, Mexican Social Security Institute. Interior de la Alameda #45 Colonia Centro ZIP code 98000, Zacatecas, Mexico
| | - Irma Gonzalez-Curiel
- Faculty of Chemical Sciences, Autonomous University of Zacatecas, Zacatecas, Mexico
| | - Luis A De Jesus-González
- Zacatecas Biomedical Research Unit, Mexican Social Security Institute. Interior de la Alameda #45 Colonia Centro ZIP code 98000, Zacatecas, Mexico
| | - Bruno Rivas-Santiago
- Zacatecas Biomedical Research Unit, Mexican Social Security Institute. Interior de la Alameda #45 Colonia Centro ZIP code 98000, Zacatecas, Mexico.
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Arora P, Bhagat S, Krishnendu MR, Singh S. Emerging trends of biomedical nanotechnology in nutrition, health monitoring and disease diagnosis. 3 Biotech 2025; 15:152. [PMID: 40336812 PMCID: PMC12052695 DOI: 10.1007/s13205-025-04291-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 03/22/2025] [Indexed: 05/09/2025] Open
Abstract
The transdisciplinary nature of nanotechnology has facilitated its application across various fields, especially in biological sciences. The primary aim of this review is to consolidate the many facets of nanomedicine, theranostics, and nanotechnology in food preservation into a unified framework and to underscore established research methodologies in the medical domain. Nanoparticles serve a crucial function in improving the bioavailability of orally delivered bioactive substances. This review demonstrated that nanoparticles can enhance the bioavailability of micronutrients, such as vitamin B12, vitamin A, folic acid, and iron. New advances in nanotechnology have made big differences in finding pathogens and killing them specifically, helping people to get better health through medication delivery and imaging, improving food packaging better so it lasts longer, and making foods healthier overall. Nanotechnology currently enhances the safety of delivering highly hazardous medicines through the use of nanozymes that exhibit antioxidant and antibacterial characteristics. Moreover, wearable devices can identify significant alterations in vital signs, medical problems, and infections occurring within the body. We anticipate that these technologies will provide physicians with enhanced direct access to crucial information about the causes of changes in vital signs or diseases, as they are directly connected to the source of the problem. This review paper thoroughly examines the latest developments in nanomaterials and nanozymes as antimicrobial agents in food science and nutrition, wound healing, illness diagnostics, imaging, and potential future uses. The paper presents a concise and structured report on nanotechnology, which will be beneficial to researchers and scientists for future research opportunities.
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Affiliation(s)
- Palak Arora
- Nanobiology and Nanozymology Research Lab, National Institute of Animal Biotechnology (NIAB), Opposite Journalist Colony, Near Gowlidoddy, Extended Q-City Road, Gachibowli, Hyderabad, Telangana 500032 India
- Regional Centre for Biotechnology (RCB), Faridabad, Haryana 121001 India
| | - Stuti Bhagat
- Nanobiology and Nanozymology Research Lab, National Institute of Animal Biotechnology (NIAB), Opposite Journalist Colony, Near Gowlidoddy, Extended Q-City Road, Gachibowli, Hyderabad, Telangana 500032 India
- Regional Centre for Biotechnology (RCB), Faridabad, Haryana 121001 India
| | - M. R. Krishnendu
- Nanobiology and Nanozymology Research Lab, National Institute of Animal Biotechnology (NIAB), Opposite Journalist Colony, Near Gowlidoddy, Extended Q-City Road, Gachibowli, Hyderabad, Telangana 500032 India
- Regional Centre for Biotechnology (RCB), Faridabad, Haryana 121001 India
| | - Sanjay Singh
- Nanobiology and Nanozymology Research Lab, National Institute of Animal Biotechnology (NIAB), Opposite Journalist Colony, Near Gowlidoddy, Extended Q-City Road, Gachibowli, Hyderabad, Telangana 500032 India
- Regional Centre for Biotechnology (RCB), Faridabad, Haryana 121001 India
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Zheng X, Deng S, Li Y, Luo Z, Gan Z, Zheng Z, Xu R, Xiao S, Cai Y, Meng J, Li L, Li C, Xue X, Dai W, Qin S, Wang M, Zeng K, Xiao Z, Xia L. Targeting m 6A demethylase FTO to heal diabetic wounds with ROS-scavenging nanocolloidal hydrogels. Biomaterials 2025; 317:123065. [PMID: 39756272 DOI: 10.1016/j.biomaterials.2024.123065] [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: 07/24/2024] [Revised: 12/26/2024] [Accepted: 12/27/2024] [Indexed: 01/07/2025]
Abstract
Chronic diabetic wounds are a prevalent and severe complication of diabetes, contributing to higher rates of limb amputations and mortality. N6-methyladenosine (m6A) is a common RNA modification that has been shown to regulate tissue repair and regeneration. However, whether targeting m6A could effectively improve chronic diabetic wound healing remains largely unknown. Here, we found a significant reduction in mRNA m6A methylation levels within human diabetic foot ulcers, and the expression level of fat mass and obesity-associated protein (FTO) was significantly increased. We identified that m6A modifies the RNA of matrix Metalloproteinase 9 (MMP9), a key factor in diabetic wound healing, to regulate its expression. Importantly, we developed a ROS-scavenging nanocolloidal hydrogel loaded with an FTO inhibitor to increase the m6A level of MMP9 RNA in wounds. The hydrogel can effectively accelerate wound healing and skin appendage regeneration in streptozotocin-induced type I diabetic rats at day 14 (approximately 98 % compared to 76.98 % in the control group) and type II diabetic db/db mice at day 20 (approximately 93 % compared to 60 % in the control group). Overall, our findings indicate that targeting m6A with ROS-scavenging hydrogel loaded with FTO inhibitor may be an effective therapeutic strategy for diabetic wound healing.
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Affiliation(s)
- Xinyao Zheng
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Shaohui Deng
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan, 523018, PR China
| | - Yuan Li
- Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, PR China
| | - Zhipeng Luo
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Ziqi Gan
- Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, PR China
| | - Zhaoping Zheng
- Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, PR China
| | - Rui Xu
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Shan Xiao
- Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, PR China
| | - Yuxiong Cai
- Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, PR China
| | - Jianfu Meng
- Department of Endocrinology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Li Li
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Changxing Li
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Xiaowen Xue
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Wei Dai
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Si Qin
- Department of Dermatology, Guangdong Second Provincial General Hospital, Guangzhou, 510317, PR China
| | - Mengying Wang
- Department of Biological Products, Chongqing Institute for Food and Drug Control, Chongqing, 401121, PR China
| | - Kang Zeng
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China.
| | - Zecong Xiao
- Nanomedicine Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, PR China.
| | - Laixin Xia
- Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, PR China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, 510515, PR China.
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6
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Chen J, Zhou Q, Cao Y, Tang X, Zhang Y, Wang L, Li J, Liang B. Identification of the potential role of PANoptosis-related genes in burns via bioinformatic analyses and experimental validation. Burns 2025; 51:107477. [PMID: 40233527 DOI: 10.1016/j.burns.2025.107477] [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: 11/15/2024] [Revised: 03/13/2025] [Accepted: 03/28/2025] [Indexed: 04/17/2025]
Abstract
BACKGROUND The treatment of burns is highly challenging due to their complex pathophysiological mechanisms. PANoptosis, as an important form of cell death, is suggested to play a crucial role in the inflammatory response and tissue damage following burns. However, the role of PANoptosis-related biomarkers in the pathophysiological processes of burns remains unclear. In this study, we aim to identify PANoptosis-related signature genes and validate them as biomarkers in burns METHODS: Burn-related datasets were obtained from the Gene Expression Omnibus(GEO) database. GSE37069 was used for bioinformatic analysis and machine learning, while GSE19743 was used specifically for external validation. A set of PANoptosis-associated genes was obtained from the GeneCards database. Three machine learning models (LASSO, RF, and SVM-RFE) and WGCNA were utilized to screen for signature genes. The diagnostic efficacy of the identified genes was assessed through receiver operating characteristic (ROC) curves. Gene Set Enrichment Analysis (GSEA) was performed to identify pathways associated with the signature genes, while single-sample gene set enrichment analysis (ssGSEA) was employed to investigate the immune landscape. Finally, Western blotting and RT-qPCR were employed to validate the signature genes. RESULTS BCL-2, CCAR1, CERK, TRIAP1, S100A8, and SNHG1 were identified as signature genes. The biological processes involving these genes mainly include endocytosis, apoptosis, and ECM receptor interaction. Immune infiltration analysis revealed that neutrophils, eosinophils, M0 macrophages, and monocytes are significantly elevated in burn samples. Additionally, these signature genes showed significant correlations with multiple immune cell types. Finally, Western blotting and RT-qPCR analysis revealed that the expression levels of BCL2, CCAR1, CERK, and TRIAP1 were significantly down-regulated in the burn groups compared to the normal groups, with the exception of S100A8. CONCLUSION Our study has identified BCL-2, CCAR1, CERK, and TRIAP1 as reliable potential biomarkers for burn injuries. These genes play crucial roles in immune response, wound healing, and anti-apoptotic mechanisms, which are key pathological processes involved in the progression of burn injuries. Specifically, BCL-2, CCAR1, CERK, and TRIAP1 have been shown to significantly impact the regulation of inflammation, the efficiency of wound repair, and the prevention of cell apoptosis during burn injury.
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Affiliation(s)
- Jiacong Chen
- Department of Anesthesiology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, China
| | - Qin Zhou
- Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
| | - Yang Cao
- Department of Anesthesiology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, China
| | - Xuexian Tang
- Department of Anesthesiology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, China
| | - Yan Zhang
- Department of Anesthesiology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, China
| | - Lin Wang
- Department of Anesthesiology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, China
| | - Junxi Li
- Department of Anesthesiology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, China
| | - Bing Liang
- Department of Anesthesiology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, China.
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Mishra T, Wairkar S. Pathogenesis, attenuation, and treatment strategies for keloid management. Tissue Cell 2025; 94:102800. [PMID: 39999656 DOI: 10.1016/j.tice.2025.102800] [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: 11/25/2024] [Revised: 02/11/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025]
Abstract
Keloid is an outcome of abnormal cellular response in the wound healing process with excessive fibroblast and collagen deposition in the dermal layer of the skin. It is characterized by a scar showing fibrous outgrowth that grows beyond the original boundaries of the wound. Thus, it is cosmetically and functionally disturbing to the patient. Keloidal development depends on various patient and environmental factors, possibly initiating abnormal wound healing. Due to abnormal wound healing, various aberrant cellular responses are observed during keloid development, like delayed inflammatory response, increased growth factors, varied cytokine level, decreased apoptosis, increased angiogenesis, and imbalanced proteinases. Bacteria and the immune system also play a role in keloid development. Advancements like single-cell RNA sequencing and transcriptomics studies have led to a better understanding of pathogenesis. In line with the complex pathogenesis, the later part of the review covers a detailed analysis of various treatment options employed for keloid, which includes silicone-based topical therapy, drug-based therapy, invasive approach (surgery), and minimally invasive therapies (radiation, laser therapy, and cryotherapy). The advantages and limitations of individual and combination therapies are also discussed. Keloids tend to re-occur after treatment; hence, follow-up is very important, making keloid treatment a complex procedure. Novel therapeutics in keloid have advantages like better efficacy of drugs, less pain, self-administration, and fewer side effects. A few nanotherapeutics advancements, such as microneedles, nanoparticles, liposomes, and exosomes, are discussed in the review.
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Affiliation(s)
- Twinkle Mishra
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L., Mehta Road, Vile Parle (W), Mumbai, Maharashtra 400056, India
| | - Sarika Wairkar
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L., Mehta Road, Vile Parle (W), Mumbai, Maharashtra 400056, India.
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Zattarin E, Sotra Z, Wiman E, Bas Y, Rakar J, Berglund L, Starkenberg A, Björk EM, Khalaf H, Oksman K, Bengtsson T, Junker JP, Aili D. Controlled release of antimicrobial peptides from nanocellulose wound dressings for treatment of wound infections. Mater Today Bio 2025; 32:101756. [PMID: 40290891 PMCID: PMC12032947 DOI: 10.1016/j.mtbio.2025.101756] [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: 12/04/2024] [Revised: 03/27/2025] [Accepted: 04/09/2025] [Indexed: 04/30/2025] Open
Abstract
Wounds are highly prone to infection, which can delay healing and lead to severe complications such as gangrene and sepsis. Non-healing wounds significantly impact patients' physical and mental well-being and place a substantial financial burden on healthcare systems. Timely and effective treatment of wound infections is critical, but the rise of antibiotic-resistant pathogens complicates this process. In this study, we investigate a potent protease resistant antimicrobial peptide (AMP), PLNC8 αβ, for the treatment of wound infections and present a strategy for localized AMP delivery using functionalized advanced nanocellulose (NC) wound dressings. Two types of NC dressings were explored: bacterial cellulose (BC) and TEMPO-oxidized nanocellulose derived from wood powder (TC). In a porcine wound infection model, PLNC8 αβ exhibited high antimicrobial activity, successfully eradicating the infection while promoting wound re-epithelialization. To achieve controlled release of PLNC8 αβ from the NC dressings, the peptides were either physisorbed directly onto the nanofibrils or encapsulated within mesoporous silica nanoparticles (MSNs) that were incorporated into the dressings. The PLNC8 αβ functionalized dressings demonstrated low cytotoxicity toward human primary fibroblasts and keratinocytes. Both BC and TC dressings showed efficient contact inhibition of bacteria but were less effective in inhibiting bacteria in suspension. In contrast, MSN-functionalized dressings, displayed significantly enhanced peptide-loading and sustained release capacities, resulting in improved antimicrobial efficacy. These findings highlight the potential of PLNC8 αβ and PLNC8 αβ-functionalized nanocellulose wound dressings for the treatment of infected wounds, offering an effective alternative to conventional antibiotic therapies.
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Affiliation(s)
- Elisa Zattarin
- Laboratory of Molecular Materials, Division of Biophysics and Bioengineering, Department of Physics, Chemistry and Biology, Linköping University, SE-581 83, Linköping, Sweden
| | - Zeljana Sotra
- Center for Disaster Medicine and Traumatology, Department of Biomedical and Clinical Sciences, Linköping University, SE-581 85, Linköping, Sweden
| | - Emanuel Wiman
- Department of Microbiology, Immunology and Reproductive Science, School of Medical Sciences, Örebro University, SE-70362, Örebro, Sweden
| | - Yagmur Bas
- Division of Materials Science, Department of Engineering Sciences and Mathematics, Luleå University of Technology, SE-971 87, Luleå, Sweden
| | - Jonathan Rakar
- Center for Disaster Medicine and Traumatology, Department of Biomedical and Clinical Sciences, Linköping University, SE-581 85, Linköping, Sweden
| | - Linn Berglund
- Division of Materials Science, Department of Engineering Sciences and Mathematics, Luleå University of Technology, SE-971 87, Luleå, Sweden
| | - Annika Starkenberg
- Center for Disaster Medicine and Traumatology, Department of Biomedical and Clinical Sciences, Linköping University, SE-581 85, Linköping, Sweden
| | - Emma M. Björk
- Division of Nanostructured Materials, Department of Physics, Chemistry and Biology (IFM), Linköping University, SE-58183, Linköping, Sweden
| | - Hazem Khalaf
- Department of Microbiology, Immunology and Reproductive Science, School of Medical Sciences, Örebro University, SE-70362, Örebro, Sweden
| | - Kristiina Oksman
- Division of Materials Science, Department of Engineering Sciences and Mathematics, Luleå University of Technology, SE-971 87, Luleå, Sweden
| | - Torbjörn Bengtsson
- Department of Microbiology, Immunology and Reproductive Science, School of Medical Sciences, Örebro University, SE-70362, Örebro, Sweden
| | - Johan P.E. Junker
- Center for Disaster Medicine and Traumatology, Department of Biomedical and Clinical Sciences, Linköping University, SE-581 85, Linköping, Sweden
| | - Daniel Aili
- Laboratory of Molecular Materials, Division of Biophysics and Bioengineering, Department of Physics, Chemistry and Biology, Linköping University, SE-581 83, Linköping, Sweden
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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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Akhtach S, Tabia Z, Belkhou R, Mabrouk KE. Bacterial exopolysaccharide and metal-doped bioactive glass nanoparticles-based electrospun membranes for chronic wound healing. Int J Pharm 2025; 676:125594. [PMID: 40228614 DOI: 10.1016/j.ijpharm.2025.125594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/30/2025] [Accepted: 04/11/2025] [Indexed: 04/16/2025]
Abstract
Healing of chronic wounds requires interactive dressings that not only meet basic biological criteria, of biocompatibility, but also offer additional functionalities such as antioxidant and antibacterial properties. In this study, three novel multifunctional nanofibrous membranes based on EPS, an α-glucan exopolysaccharide produced by Lacticaseibacillus rhamnosus P14, blended with PEO as a co-polymer were successfully developed using electrospinning. The membranes incorporated Cu or Ag-doped bioactive glass (BG) nanoparticles, to enhance their functionalities. The structural and thermal properties of the electrospun membranes were characterized using FT-IR, TGA, and DSC analysis. In addition, the surface morphology, fiber size, and porosity were examined by SEM analysis. Additionally, their biological properties, including antioxidant and antibacterial activities, were thoroughly investigated. SEM confirmed the effective electrospinning of the EPS-PEO and EPS-PEO-BG blends from aqueous solutions using optimized process parameters, resulting in the successful incorporation of the BG nanoparticles and uniform fibers with average diameter ranging from 270 to 352 nm. Moreover, DPPH RSA and FRAP assays showed a significant antioxidant capacity for all prepared membranes which is attributed to the EPS component. Moreover, the antibacterial activity revealed a notable inhibition against E. coli and S. aureus after 24 h exposure to the composite membranes. This work presents a novel synergistic approach to developing multifunctional wound dressing by combining the antioxidant properties of EPS, the antibacterial activity of ion-doped bioactive glass nanoparticles, and structural benefits of electrospinning.
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Affiliation(s)
- Sihame Akhtach
- Laboratory of Biotechnology, Environment, Agrifood, and Health (LBEAS) Faculty of Science Dhar Mahraz, University Sidi Mohamed Ben Abdallah, Fes, Morocco.
| | | | - Rajae Belkhou
- Laboratory of Biotechnology, Environment, Agrifood, and Health (LBEAS) Faculty of Science Dhar Mahraz, University Sidi Mohamed Ben Abdallah, Fes, Morocco.
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11
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Khajornpipat P, Reamtong O, Aunpad R. Rational engineering unlocks the therapeutic potential of WHP1: A revolutionary peptide poised to advance wound healing. PLoS One 2025; 20:e0323363. [PMID: 40367225 PMCID: PMC12077786 DOI: 10.1371/journal.pone.0323363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Accepted: 04/07/2025] [Indexed: 05/16/2025] Open
Abstract
Treatment of chronic or non-healing wounds has faced a considerable clinical challenge and impose several detrimental effects on individuals, society, the healthcare system, and the economy. Bioactive peptides have been employed to accelerate wound healing in active wound treatment efficiently and effectively. In the current study, a novel wound-healing peptide, WHP1, was designed from 23 existing wound-healing peptides by a rational template-assisted approach. It demonstrated the ability to enhance migration and proliferation of human keratinocyte cell lines (HaCaT) without exhibiting cytotoxic effects on human red blood cells and HaCaT cells. By quantitative proteomic analysis, WHP1 exerted a multifaceted role on diverse cellular processes in human keratinocyte. Notably, it increased the expression of intracellular proteins of HaCaT cells involved in cell cycle regulation and focal adhesion, including centromeric histone H3 variant CENPA, ubiquitin-conjugating enzyme E2 C, thyroid receptor-interacting protein 6, and ribosomal components essential for cell adhesion and migration. WHP1 upregulated the key enzyme glyceraldehyde-3-phosphate dehydrogenase, orchestrating metabolic biosynthesis particularly glycolysis, cell cycle regulation, and cytoskeletal processes. An intriguing observation was the antioxidant activity of WHP1, protecting cells from reactive oxygen species-induced senescence. This is consistent with the upregulation of GAPDH expression and reduction of histone H2A.J levels. WHP1 also stimulated macrophages to secrete transforming growth factor-β (TGF-β), a crucial growth factor necessary for the remodeling phase of wound healing. This investigation highlighted the feasibility of rational design to create novel wound-healing peptides. Such advancements hold promise for improving patients' quality of life and elevating the standard of care in contemporary healthcare.
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Affiliation(s)
- Patcharin Khajornpipat
- Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, Thailand
| | - Onrapak Reamtong
- Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Ratchaneewan Aunpad
- Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, Thailand
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12
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Rojas-Velis N, Cárdenas-García C, Pérez E, Toledo JR, Medina MÁ, Astuya-Villalón A, Abdala-Díaz RT. In Vitro Evaluation of the Healing Potential and Proteomic Study of Quercus robur L. Leaf Extracts in Human Keratinocytes. Molecules 2025; 30:2152. [PMID: 40430324 PMCID: PMC12113831 DOI: 10.3390/molecules30102152] [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: 03/11/2025] [Revised: 05/07/2025] [Accepted: 05/12/2025] [Indexed: 05/29/2025] Open
Abstract
(1) Background: This study evaluated the potential of an aqueous extract from Quercus robur L. leaves for chronic wound healing. Its composition, rich in bioactive compounds (tannins and flavonoids), confers antioxidant and antimicrobial properties. (2) Methods: The toxicity and ability of the extract to enhance cell migration were tested in human keratinocytes (HaCaT cell line). Additionally, a proteomic analysis was performed on treated cells. (3) Results: The extract exhibited low cytotoxicity (IC50 = 943 µg·mL-1) compared to other plant extracts. At 5 mg·mL-1, it significantly accelerated wound closure at 8 h, surpassing negative control and Reoxcare; however, results were comparable at 12 h. Proteomic analysis identified 117 differentially expressed proteins (21 upregulated, 96 downregulated) involved in essential processes such as cell migration, blood clotting, and cholesterol biosynthesis. Specifically, the extract increased the expression of CYP51A1, LSS, and SQLE, while inhibiting Delta (14)-sterol reductase, key enzymes in cholesterol metabolism, suggesting a potential mechanism for tissue regeneration. (4) Conclusions: The aqueous extract of Q. robur leaves shows promise as a natural therapeutic agent for chronic wound healing, potentially aiding tissue regeneration and modulation of cholesterol metabolism.
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Affiliation(s)
- Nelson Rojas-Velis
- Biotoxins Laboratory, Faculty of Natural and Oceanographic Sciences, Center for Oceanographic Research COPAS COASTAL, University of Concepción, Concepción 4070386, Chile; (N.R.-V.); (A.A.-V.)
| | - Casimiro Cárdenas-García
- Central Research Support Services (SCAI), University of Málaga, Campus de Teatinos s/n, E-29071 Málaga, Spain;
| | - Erik Pérez
- Biotechnology and Biopharmaceuticals Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile; (E.P.); (J.R.T.)
| | - Jorge R. Toledo
- Biotechnology and Biopharmaceuticals Laboratory, Pathophysiology Department, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción 4030000, Chile; (E.P.); (J.R.T.)
| | - Miguel Ángel Medina
- Department of Molecular Biology and Biochemistry, Faculty of Science, Universidad de Málaga, Andalucía Tech, E-29071 Málaga, Spain;
| | - Allisson Astuya-Villalón
- Biotoxins Laboratory, Faculty of Natural and Oceanographic Sciences, Center for Oceanographic Research COPAS COASTAL, University of Concepción, Concepción 4070386, Chile; (N.R.-V.); (A.A.-V.)
| | - Roberto T. Abdala-Díaz
- Department of Ecology, Faculty of Sciences, Institute of Biotechnology and Blue Development (IBYDA), Universidad de Málaga, Campus de Teatinos s/n, E-29071 Málaga, Spain
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13
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Pereira AR, Pires PC, Hameed H, Lopes D, Lopes J, Sousa-Oliveira I, Babaie S, Mazzola P, Veiga F, Paiva-Santos AC. Injectable nanocomposite hydrogels for targeted intervention in cancer, wound healing, and bone and myocardial tissue engineering. Drug Deliv Transl Res 2025:10.1007/s13346-025-01864-2. [PMID: 40358831 DOI: 10.1007/s13346-025-01864-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2025] [Indexed: 05/15/2025]
Abstract
Despite current medicine's fast-paced advances, many acute and chronic illnesses still lack truly effective and safe therapies. Cancer treatments often lead to off-target healthy tissue damage and poor therapeutic outcomes, wound standard treatments generally demonstrate poor healing efficacy and increased susceptibility to infection, and bone tissue engineering and myocardial tissue engineering can result in immunological rejection and limited availability. To tackle these issues, injectable hydrogels have emerged, and through the incorporation of nanoparticles, nanocomposite hydrogels have appeared as versatile platforms, offering improved biocompatibility, mechanical strength, stability, and precise controlled drug release, as well as targeted delivery with increased drug retention at the site of action, reducing systemic drug distribution to non-target sites. With the ability to deliver a diverse range of therapeutic entities, including low molecular weight drugs, proteins, antibodies, and even isolated cells, injectable nanocomposite hydrogels have revolutionized current therapies, working as multifunctional platforms capable of improving efficacy and safety in cancer treatment, including in chemotherapy, immunotherapy, photothermal therapy, magnetic hyperthermia, photodynamic therapy, chemodynamic therapy, radiotherapy, molecularly targeted therapy, and after tumor surgical removal, and in general, chronic diabetic or tumor-induced wound healing, as well as in bone tissue engineering and myocardial tissue engineering. This review provides a thorough summary and critical insight of current advances on injectable nanocomposite hydrogels as an innovative approach that could bring substantial contributions to biomedical research and clinical practice, with a focus on their applications in cancer therapy, wound healing management, and tissue engineering.
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Affiliation(s)
- Ana Rita Pereira
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga de Santa Comba, 3000 - 548, Coimbra, Portugal
| | - Patrícia C Pires
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga de Santa Comba, 3000 - 548, Coimbra, Portugal.
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000 - 548, Coimbra, Portugal.
- Department of Medical Sciences, Faculty of Health Sciences, RISE-Health, University of Beira Interior, Av. Infante D. Henrique, 6200 - 506, Covilhã, Portugal.
| | - Huma Hameed
- Faculty of Pharmaceutical Sciences, University of Central Punjab (UCP), Lahore, 54000, Pakistan
| | - Daniela Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga de Santa Comba, 3000 - 548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000 - 548, Coimbra, Portugal
| | - Joana Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga de Santa Comba, 3000 - 548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000 - 548, Coimbra, Portugal
| | - Inês Sousa-Oliveira
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga de Santa Comba, 3000 - 548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000 - 548, Coimbra, Portugal
| | - Soraya Babaie
- Physical Medicine and Rehabilitation Research Center, Tabriz University of Medical Sciences, Tabriz, 51368, Iran
| | - Priscila Mazzola
- Faculty of Pharmaceutical Sciences, Universidade Estadual de Campinas, Campinas, SP, 13083 - 970, Brazil
| | - Francisco Veiga
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga de Santa Comba, 3000 - 548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000 - 548, Coimbra, Portugal
| | - Ana Cláudia Paiva-Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Azinhaga de Santa Comba, 3000 - 548, Coimbra, Portugal.
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000 - 548, Coimbra, Portugal.
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14
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Machado P, Ribeiro FN, Giublin FCW, Mieres NG, Tonin FS, Pontarolo R, Sari MHM, Lazo REL, Ferreira LM. Next-Generation Wound Care: A Scoping Review on Probiotic, Prebiotic, Synbiotic, and Postbiotic Cutaneous Formulations. Pharmaceuticals (Basel) 2025; 18:704. [PMID: 40430523 PMCID: PMC12114949 DOI: 10.3390/ph18050704] [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: 04/03/2025] [Revised: 05/04/2025] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: Chronic wounds represent a significant socioeconomic burden, affecting 1-2% of the global population. Wound healing is a complex process involving inflammation, cell proliferation, and tissue remodeling, but factors such as infections, diabetes, aging, and poor nutrition can impair recovery, leading to chronic wounds. Given these challenges, researchers have explored topical probiotics, synbiotics, and postbiotics as alternatives strategies. Strains like Lactobacillus and Bifidobacterium contribute to skin restoration by producing antimicrobial, anti-inflammatory, and immunomodulatory compounds, offering a novel approach to cutaneous restoration. Our study aims to address the potential effects of topical probiotic, synbiotic, and postbiotic formulations for wound healing applications by means of a broad scoping review and evidence-gap mapping. Methods: A systematic literature search of preclinical studies (in vitro and in vivo) was performed in PubMed, Scopus, and Web of Science (January 2025), yielding 3052 articles after duplicates removal, of which 44 met the inclusion criteria. Results: These studies were published between 1986 and 2024, mostly by China (27.3%) and Iran (25.0%). Probiotics were frequently evaluated among the studies included (47.7%) (with Lactobacillus plantarum being the most assessed strain), followed by postbiotics (36.4%) (with predominant use of cell-free supernatants) and synbiotics (15.9%) (especially fructooligosaccharides). Dosage forms included gels (44.4%), films (15.6%), and ointments (13.3%). Conclusions: Most studies indicate that probiotics, synbiotics, and postbiotics have antimicrobial and anti-inflammatory properties, while promoting angiogenesis, tissue regeneration, and skin barrier restoration. The use of different delivery systems may additionally enhance therapeutic outcomes by accelerating wound closure, reducing bacterial load, and modulating immune response. However, methodological limitations in animal studies highlight the need for greater experimental rigor. Further robust clinical trials are essential to confirm efficacy and safety before clinical application of these formulations.
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Affiliation(s)
- Patrícia Machado
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Curitiba 80210-170, Brazil; (P.M.); (N.G.M.); (R.P.); (M.H.M.S.)
| | - Felipe Neme Ribeiro
- Departamento de Medicina, Universidade Federal do Paraná, Curitiba 80210-170, Brazil;
| | | | - Naomi Gerzvolf Mieres
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Curitiba 80210-170, Brazil; (P.M.); (N.G.M.); (R.P.); (M.H.M.S.)
| | - Fernanda Stumpf Tonin
- Health and Technology Research Center (H&TRC), Escola Superior de Tecnologia da Saúde (ESTeSL-IPL), 1990-096 Lisbon, Portugal;
- Pharmacy and Pharmaceutical Technology Department, Social and Legal Pharmacy Section, University of Granada, 18012 Granada, Spain
| | - Roberto Pontarolo
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Curitiba 80210-170, Brazil; (P.M.); (N.G.M.); (R.P.); (M.H.M.S.)
| | - Marcel Henrique Marcondes Sari
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Curitiba 80210-170, Brazil; (P.M.); (N.G.M.); (R.P.); (M.H.M.S.)
| | - Raul Edison Luna Lazo
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Curitiba 80210-170, Brazil; (P.M.); (N.G.M.); (R.P.); (M.H.M.S.)
| | - Luana Mota Ferreira
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Curitiba 80210-170, Brazil; (P.M.); (N.G.M.); (R.P.); (M.H.M.S.)
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15
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Suryaningtyas IT, Jasmadi, Dayarathne LA, Marasinghe CK, Je JY. Mussels as sustainable marine resources for bioactive peptides for health and the food industry. Food Funct 2025; 16:3255-3272. [PMID: 40261071 DOI: 10.1039/d4fo05397d] [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: 04/24/2025]
Abstract
The growing need for sustainable protein sources has led to increased interest in marine-based alternatives, particularly those with bioactive properties. Mussels, known for their abundance and environmental sustainability, have gained attention as potential sources for bioactive peptides (BAPs). This review focuses on the current research surrounding BAPs derived from marine mussels, exploring their applications in human health and the food industry. Through a comprehensive analysis of the existing literature, the review discusses the ecological significance of mussels, their nutritional value, and the health benefits of mussel-derived peptides, which include antioxidant, anti-inflammatory, anti-osteoporosis, and cardiovascular effects. Additionally, the review examines methods for extracting these peptides, their commercial availability, and the challenges faced in the field, along with future research directions. While mussels have traditionally been consumed for their nutritional benefits, the scientific investigation into their potential for producing BAPs is relatively recent. These peptides, obtained through processes like fermentation and hydrolysis, offer promising applications in functional foods and nutraceuticals. However, further research is necessary to optimize extraction techniques, overcome commercialization hurdles, and fully realize the potential of mussels as sustainable sources of BAPs for enhancing human health.
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Affiliation(s)
- Indyaswan Tegar Suryaningtyas
- Research Center for Marine-Integrated Bionics Technology, Pukyong National University, Busan 48513, Republic of Korea
- Research Center for Food Technology and Processing, National Research and Innovation Agency, Yogyakarta, 55861, Indonesia
- Department of Food and Life Science, Pukyong National University, Busan 48513, Republic of Korea
| | - Jasmadi
- Research Center for Food Technology and Processing, National Research and Innovation Agency, Yogyakarta, 55861, Indonesia
- Department of Food and Life Science, Pukyong National University, Busan 48513, Republic of Korea
| | - Lakshi Ayoda Dayarathne
- Department of Food and Life Science, Pukyong National University, Busan 48513, Republic of Korea
| | | | - Jae-Young Je
- Major of Human Bioconvergence, Division of Smart Healthcare, Pukyong National University, Busan 48513, Republic of Korea.
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16
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Dong L, Zhang G, Shen Z, Hong X, Xing Y, Wu Y, Yang W, Zhang B, Shi Z. Degradation of WE43 Magnesium Alloy in Vivo and Its Degradation Products on Macrophages. ACS OMEGA 2025; 10:17280-17295. [PMID: 40352546 PMCID: PMC12059945 DOI: 10.1021/acsomega.4c09349] [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: 10/21/2024] [Revised: 04/07/2025] [Accepted: 04/16/2025] [Indexed: 05/14/2025]
Abstract
Due to their biocompatibility, biodegradability, and suitable mechanical properties, magnesium-based biodegradable implants are emerging as a promising alternative to traditional metal implants. The Mg-4Y-3RE (WE43) biodegradable alloy is among the most extensively studied and widely utilized magnesium alloys in clinical applications. As an absorbable and degradable metallic material, magnesium alloys undergo gradual degradation, wear, and fracture within the body. These alloys reduce the long-term risks associated with permanent implants but generate insoluble byproducts that accumulate in surrounding tissues. Following the implantation of magnesium alloys, granulation tissue and fibrous encapsulation typically form around the material. However, limited research has addressed the interaction between insoluble byproducts of magnesium alloys and macrophages. This study focused on the biological effects of macrophages during the second stage of the host inflammatory response in the degradation process of magnesium alloy. Using subcutaneous implantation of WE43 magnesium alloy sheets, observations were made regarding the degradation components, morphological changes in surrounding tissues, and the biological effects of macrophages upon phagocytosis of insoluble byproducts. The primary degradation products of WE43 in vivo were identified as Ca3 (PO4)2, Mg3(PO4)2, Na3PO4, NaCa (PO4), MgSO4, MgCO3, NaCl, Mg24Y5, and Mg12YNd. Postimplantation, levels of IL-1β and IL-18 in adjacent tissues significantly increased (p < 0.05). By 8 weeks, compared to nitinol alloy, significant thickening of the fibrous capsule (p < 0.05) was observed, accompanied by substantial inflammatory cell infiltration, vascularization, and the presence of macrophages and multinucleated giant cells. Macrophages were observed extending pseudopodia to enclose and phagocytose particles, forming phagosomes and creating a relatively isolated microenvironment around the engulfed substances, where further particle degradation occurred. Following the phagocytosis of degradation products, macrophages exhibited increased lysosome numbers, mitochondrial swelling and damage, phagolysosome formation, and autophagosome development. Furthermore, the degradation products were observed to induce elevated reactive oxygen species (ROS) production in macrophages, activation of P2X7 receptors, enhanced IL-6 secretion, endoplasmic reticulum stress, autophagy, and activation of the NLRP3 inflammasome pathway. This study provides novel insights and contributes a theoretical foundation for a more comprehensive understanding of magnesium alloy degradation in vivo.
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Affiliation(s)
- Li Dong
- Department
of Cardiology, The Fourth Affiliated Hospital
of Harbin Medical University, Harbin 150001, China
| | - Guangde Zhang
- Department
of Cardiology, The Fourth Affiliated Hospital
of Harbin Medical University, Harbin 150001, China
| | - Zhiyuan Shen
- Department
of Cardiology, The Fourth Affiliated Hospital
of Harbin Medical University, Harbin 150001, China
| | - Xiaojian Hong
- Department
of Cardiology, The Fourth Affiliated Hospital
of Harbin Medical University, Harbin 150001, China
| | - Yongli Xing
- Department
of Medical Imaging, Second Hospital of Harbin, Harbin 150056, China
| | - Yue Wu
- Department
of Cardiology, The Fourth Affiliated Hospital
of Harbin Medical University, Harbin 150001, China
| | - Wei Yang
- Department
of Cardiology, The Fourth Affiliated Hospital
of Harbin Medical University, Harbin 150001, China
| | - Binmei Zhang
- Department
of Cardiology, The Fourth Affiliated Hospital
of Harbin Medical University, Harbin 150001, China
| | - Zhiyu Shi
- Department
of Cardiology, The First Affiliated Hospital
of Harbin Medical University, Harbin 150007, China
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17
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Martin EM, Chang J, González A, Genovese F. Circulating collagen type I fragments as specific biomarkers of cardiovascular outcome risk: Where are the opportunities? Matrix Biol 2025; 137:19-32. [PMID: 40037418 PMCID: PMC11986567 DOI: 10.1016/j.matbio.2025.03.001] [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: 11/22/2024] [Revised: 02/24/2025] [Accepted: 03/01/2025] [Indexed: 03/06/2025]
Abstract
Collagen type I (COL1) is the most abundant protein in the human body and is a main component in the extracellular matrix. The COL1 structure vastly influences normal tissue homeostasis, and changes in the matrix drive progression in multiple diseases. Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity in many Western countries; alterations in the extracellular matrix turnover processes, including COL1, are known to influence the pathophysiological processes leading to CVD outcome. Peptides reflecting COL1 formation and degradation have been established and explored for over two decades in CVD. This review aims to combine and assess the evidence for using COL1-derived circulating peptides as biomarkers in CVD. Secondly, the review identifies existing pitfalls, and evaluates future opportunities for improving the technical characteristics and performance of the biomarkers for implementation in the clinical setting.
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Affiliation(s)
- Emily M Martin
- Nordic Bioscience A/S, Herlev, Denmark; Institute of Biomedical Science, University of Copenhagen, Copenhagen, Denmark.
| | - Joan Chang
- Manchester Cell-Matrix Centre, Division of Molecular and Cellular Function, University of Manchester, Manchester, UK
| | - Arantxa González
- Centre for Applied Medical Research (CIMA) Universidad de Navarra, Department of Cardiology and Cardiac Surgery, Clínica Universidad de Navarra, Department of Pathology Anatomy and Physiology Universidad de Navarra and IdiSNA, Pamplona, Navarra (Spain); CIBERCV, Instituto de Salud Carlos III, Madrid Spain
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18
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Parmal S, Subbappa P, Nikam V, Tarwate Y, Barhate K, Wagh S, Gholap AD, Dua K, Singh SK, Parikh D, Shaikh M, Khan TK, Rajput A. Hyaluronic acid based approaches for wound healing: A comprehensive review. Int J Biol Macromol 2025; 306:141625. [PMID: 40049471 DOI: 10.1016/j.ijbiomac.2025.141625] [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: 11/08/2024] [Revised: 02/19/2025] [Accepted: 02/27/2025] [Indexed: 05/11/2025]
Abstract
Wound healing is a natural, however complex, tissue repair and regeneration mechanism. Understanding the cascade of biological events associated with wound healing facilitates scientists in designing topical skin formulations with enhanced therapeutic outcomes. In recent years, several innovative approaches have been utilized to treat wounds. Hyaluronic acid (HA)-based formulations have shown promising results. The current manuscript provides a systematic review of various aspects of HA, including its structure, synthesis, mechanism involved in wound healing, and various formulations developed using HA to treat wounds. Covered are innovative treatment strategies explicitly emphasizing nanocarrier-based approaches. Various patents wherein HA has been used to treat wounds are also summarized with the help of a Google patent search. Diving deep, clinical perspectives, toxicity aspects, and application of computational chemistry in HA research are also discussed.
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Affiliation(s)
- Samay Parmal
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Praveen Subbappa
- Alliance Management and Supply Chain, Azurity Pharmaceuticals, Inc., 8 Cabot Road, Suite 2000, Woburn, MA 01801, USA
| | - Vaidehi Nikam
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Yash Tarwate
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Kunika Barhate
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Shrutika Wagh
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India
| | - Amol D Gholap
- Department of Pharmaceutics, St. John Institute of Pharmacy and Research, Palghar 401404, Maharashtra, India; Department of Pharmaceutics, Amrutvahini College of Pharmacy, Sangamner 422608, Maharashtra, India
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology Sydney, Ultimo 2007, Australia
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India; School of Medical and Life Sciences, Sunway University, 47500 Sunway City, Malaysia
| | - Dhaivat Parikh
- Department of Pharmaceutics, Institute of Pharmacy, Nirma University, S.G. Highway, Ahmedabad 382481, Gujarat, India
| | - Mushtaque Shaikh
- Department of Pharmaceutical Chemistry, Vivekanand Education Society's College of Pharmacy, Chembur (East), Mumbai 400074, Maharashtra, India
| | - Tamanna K Khan
- Department of Chemistry, Guru Nanak Khalsa College of Art Science and Commerce (Autonomus), Matunga (East), Mumbai 400019, Maharashtra, India
| | - Amarjitsing Rajput
- Department of Pharmaceutics, Bharti Vidyapeeth Deemed to be University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra, India.
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19
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Edo GI, Ndudi W, Makia RS, Ainyanbhor IE, Yousif E, Gaaz TS, Isoje EF, Opiti RA, Akpoghelie PO, Igbuku UA, Ahmed DS, Essaghah AEA, Umar H. Carrageenan-Based Hydrogels for Advanced Wound Healing and Controlled Drug Delivery in Tissue Engineering. J Biomed Mater Res B Appl Biomater 2025; 113:e35594. [PMID: 40369882 DOI: 10.1002/jbm.b.35594] [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: 08/15/2024] [Revised: 04/10/2025] [Accepted: 05/01/2025] [Indexed: 05/16/2025]
Abstract
Carrageenan (CGN) is a high molecular weight polysaccharide that is extracted from red seaweeds. It is made up of D-galactose residues connected by β-1,4 and α-1,3 galactose-galactose bonds. As a result of its ability to thicken, emulsify, and stabilize food, it is frequently used as a food additive in processed food. Its consumption has surged in recent years due to the Western diet's (WD) spread. Carrageenan has the ability to change the thickness of the mucus barrier, the composition of the gut microbiota, and the innate immune pathway that causes inflammation. Also, its inherent qualities, which include biodegradability, biocompatibility, resemblance to native glycosaminoglycans, antioxidants, anticancer, immunomodulatory, and anticoagulant activities, Carrageenan-based hydrogels have been the subject of numerous investigations lately for biomedical applications. The brittle hydrogel and uncontrollably exchanged ions, however, are two drawbacks to the application of this polysaccharide, but these can be avoided by making straightforward chemical changes to polymer networks, which create chemically bonded hydrogels with important mechanical characteristics and regulated degradation rates. Furthermore, the addition of diverse kinds of nanoparticles, as well as polymer networks, to carrageenan hydrogels results in hybrid platforms with noteworthy mechanical, chemical, and biological characteristics, which qualify them as appropriate biomaterials for tissue engineering (TE), drug delivery (DD), and also wound healing applications. Our goal in this article is to provide an overview of the most current developments in hybrid carrageenan-based platforms and several chemical modification techniques for TE and DD applications.
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Affiliation(s)
- Great Iruoghene Edo
- Department of Chemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
- Department of Chemistry, College of Sciences, Al-Nahrain University, Baghdad, Iraq
| | - Winifred Ndudi
- Department of Chemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Raghda S Makia
- Department of Plant Biotechnology, College of Biotechnology, Al-Nahrain University, Baghdad, Iraq
| | - Irene Ebosereme Ainyanbhor
- Faculty of Science, Department of Biochemistry, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Emad Yousif
- Department of Chemistry, College of Sciences, Al-Nahrain University, Baghdad, Iraq
| | - Tayser Sumer Gaaz
- Department of Prosthetics and Orthotics Engineering, College of Engineering and Technologies, Al-Mustaqbal University, Babylon, Iraq
| | - Endurance Fegor Isoje
- Department of Biochemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Nigeria
| | - Rapheal Ajiri Opiti
- Department of Chemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Patrick Othuke Akpoghelie
- Faculty of Science, Department of Food Science and Technology, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Ufuoma Augustina Igbuku
- Department of Chemistry, Faculty of Science, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Dina S Ahmed
- Department of Chemical Industries, Institute of Technology-Baghdad, Middle Technical University, Baghdad, Iraq
| | - Arthur Efeoghene Athan Essaghah
- Faculty of Environmental Sciences, Department of Urban and Regional Planning, Delta State University of Science and Technology, Ozoro, Delta State, Nigeria
| | - Huzaifa Umar
- Operational Research Centre in Healthcare, Near East University, Nicosia, Cyprus
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20
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Kulatunge DR, Jayawardana KH, Abeysekera AM, Wijeyaratne SC, Gunaherath GMKB. In-vitro cell migration enhancing constituents from Decalepis hamiltonii, a plant used in the preparation of 'Pinda oil', a medicinal oil used in Ayurveda for wound management. Nat Prod Res 2025; 39:2990-2996. [PMID: 38235612 DOI: 10.1080/14786419.2024.2305220] [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: 09/07/2023] [Revised: 12/16/2023] [Accepted: 01/05/2024] [Indexed: 01/19/2024]
Abstract
Decalepis hamiltonii, Wight & Arn. (Apocyanaceae) is a one of the raw materials used in the preparation of 'Pinda oil', a medicinal oil which is used for treatment of wounds in Ayurveda. Of the hexanes, dichloromethane, and ethyl acetate extracts derived from the plant raw materials used to prepare 'Pinda oil', the hexanes extract of D. hamiltonii exhibited the highest mean percentage wound closure (75.1 ± 2.9) compared to the negative controls (1% DMSO in DMEM, 4.2 ± 1.2 and 100% DMEM, 4.1 ± 0.9) in the scratch wound assay (SWA). Fractionation of the hexanes extract of stem of D. hamiltonii led to the isolation of 2-hydroxy-4-methoxybenzaldehyde (1) and a mixture of long chain esters of lupeol (2), which showed enhanced cell migration in SWA. It was observed that the esters of lupeol bind to the cell membrane and/or enter the cells during the SWA. It was found that these constituents are also present in 'Pinda oil' which may contribute to the enhancement of wound healing activity of 'Pinda oil'.
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Affiliation(s)
- D R Kulatunge
- Department of Chemistry, The Open University of Sri Lanka, Nugegoda, Sri Lanka
| | | | - Ajita M Abeysekera
- Department of Chemistry, Sri Jayewardenepura University, Nugegoda, Sri Lanka
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21
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Arayesh S, Tanhaei B, Khoshkho SM, Shahrak MN, Ayati A, Far SK. Enhanced dual-drug loaded κ-carrageenan/agar hydrogel films for wound dressing: Optimizing swelling and drug release. Int J Biol Macromol 2025; 306:141295. [PMID: 39984103 DOI: 10.1016/j.ijbiomac.2025.141295] [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: 06/25/2024] [Revised: 12/26/2024] [Accepted: 02/18/2025] [Indexed: 02/23/2025]
Abstract
This study presents the development of antibacterial hydrogel films based on natural biopolymers, κ-carrageenan and agar, crosslinked with KCl for wound healing applications. The hydrogels were loaded with tetracycline (TC) and clove extract to enhance antimicrobial properties, while the addition of Triton X-100 (TX-100) improved drug solubility and bioavailability, leading to higher drug release rates. Swelling behavior was evaluated in distilled water (DW), simulated wound fluid (SWF), and phosphate-buffered saline (PBS), with maximum swelling observed at 399 %, 222 %, and 124 %, respectively. Swelling kinetics followed pseudo-second-order and Korsmeyer-Peppas models, suggesting a Fickian diffusion mechanism. Drug release profiles were influenced by medium type and clove concentration, with the highest release observed in SWF at a clove concentration of 8 mg L-1. Antimicrobial tests demonstrated significant inhibition of E. coli and S. aureus, supporting the hydrogel's potential for infection control in wounds. Mechanical analysis showed that the hydrogels could withstand a peak force of 438.364 g, while water vapor permeability tests suggested an optimal moisture environment conducive to healing. The developed hydrogel films have a high potential for wound care, combining enhanced drug release, effective antimicrobial activity, and mechanical durability.
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Affiliation(s)
- Shirin Arayesh
- Department of Chemical Engineering, Faculty of Advanced Technologies, Quchan University of Technology, Quchan, Iran
| | - Bahareh Tanhaei
- Department of Chemical Engineering, Faculty of Advanced Technologies, Quchan University of Technology, Quchan, Iran.
| | - Saeedeh Movaghar Khoshkho
- Department of Chemical Engineering, Faculty of Advanced Technologies, Quchan University of Technology, Quchan, Iran
| | - Mahdi Niknam Shahrak
- Department of Chemical Engineering, Faculty of Advanced Technologies, Quchan University of Technology, Quchan, Iran
| | - Ali Ayati
- Department of Chemical Engineering, Faculty of Advanced Technologies, Quchan University of Technology, Quchan, Iran
| | - Somayeh Khazaei Far
- Department of Chemical Engineering, Faculty of Advanced Technologies, Quchan University of Technology, Quchan, Iran
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22
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Jansz C, McGuiness W, Cleary S. Concordance treatment continuum: A proposed clinical outcome to boost concordance with compression therapy. J Tissue Viability 2025; 34:100907. [PMID: 40300491 DOI: 10.1016/j.jtv.2025.100907] [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: 03/29/2025] [Accepted: 04/11/2025] [Indexed: 05/01/2025]
Abstract
Research by MacGregor (2013)and shows that 1-3 % of the population experience chronic venous insufficiency (CVI). Among these individuals, 60-80 % develop venous leg ulcers (VLU), according to Nelson and Adderley (2016). However, patient adherence to compression therapy (CT)-the gold standard treatment for VLUs-remains low at 39.9 %, even for those whose ulcers have healed. This lack of concordance heightens the risk of ulcer recurrence (Erickson et al., 1995; Finlayson et al., 2014; Kapp et al., 2013), presenting a significant and costly challenge for healthcare systems (Smith & McGuiness, 2010). Compression therapy works by enhancing venous return and reducing both venous pressure and stasis. Two Delphi studies conducted revealed a combined 105 overall factors. Whilst clinicians and patients identified different factors that influence long term concordance, there was consensus around factors that contribute to comfort, motivation, access to health care, and clinician attributes. Further research is needed to combine these elements into a concise clinical guideline, a concordance treatment continuum, to assist both the clinician and patient to achieve long term concordance with CT, to improve clinical outcomes of VLU reoccurrence.
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Affiliation(s)
- Chloe Jansz
- Healthcare United - Director of Nursing Services and Nurse Practitioner, 2/44 Eleanor St, Footscray, VIC, 3011, Australia.
| | - William McGuiness
- Adjunct A/Prof La Trobe University, Plenty Road, Bundoora, VIC, Australia
| | - Sonja Cleary
- RMIT University- Dean of Students STEM College, Building 215, Level 4, Plenty Road, Bundoora, Melbourne, VIC, Australia
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23
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Wang R, Chen M, Chu Y, Pan W, Chen F. The design principle of natural polysaccharide hydrogels for promoting wound healing: a prospective review. J Mater Chem B 2025; 13:4722-4738. [PMID: 40145143 DOI: 10.1039/d4tb02576h] [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: 03/28/2025]
Abstract
Acute skin injuries and chronic non-healing wounds are common in daily life, posing significant physical trauma to patients and creating substantial social and economic burdens. Polysaccharide-based hydrogels not only maintain optimal moisture levels for wound recovery but also act as effective barriers against bacterial infection. Polysaccharides, with their unique properties such as biocompatibility, biodegradability, and non-toxicity, are promising materials for constructing hydrogels designed for wound healing. This review discusses wound physiology, key design factors for wound-healing hydrogels, and the fundamental principles of hydrogel gelation. It also provides an overview of the current applications of polysaccharide-based hydrogels-including those derived from hyaluronic acid, chitosan, sodium alginate, cellulose, glucose, and starch-as advanced wound dressings. Finally, the review outlines current challenges and future research directions for polysaccharide-based hydrogels in wound healing, aiming to inspire further exploration and innovation in this field.
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Affiliation(s)
- Ruyue Wang
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China.
| | - Maohu Chen
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China.
| | - Yonghua Chu
- The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310027, China
| | - Wensheng Pan
- Department of Gastroenterology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Institute of gastrointestinal diseases, Hangzhou medical college, Zhejiang Provincial Engineering Laboratory of Diagnosis, Treatment and Pharmaceutical Development of Gastrointestinal Tract Tumors, Hangzhou 310014, P. R. China.
| | - Feng Chen
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China.
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24
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Murakami J, Tanaka T, Tani K, Ueno K, Yamamoto N, Yoshimine S, Purba MS, Sunahara H, Hoshii Y, Hamano K. Pilot study of autologous multilayered fibroblast sheet transplantation for reinforcing bronchial stump healing after pulmonary lobectomy in a canine model. Gen Thorac Cardiovasc Surg 2025:10.1007/s11748-025-02145-y. [PMID: 40232674 DOI: 10.1007/s11748-025-02145-y] [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: 03/01/2025] [Accepted: 04/02/2025] [Indexed: 04/16/2025]
Abstract
OBJECTIVE Bronchopleural fistula (BPF) is a serious complication that can occur after lung resection. This pilot study aimed to evaluate the effectiveness of autologous multilayered fibroblast sheet transplantation in reinforcing bronchial stump healing after lung resection in a canine model. METHODS Four beagles underwent left caudal lobe excision. Two dogs received autologous multilayered fibroblast sheet transplantation on the stapled bronchial stump, while two served as controls. Fibroblast sheets generated from autologous oral mucosal fibroblasts were optimized for growth factor secretion. Fourteen days after lobectomy, the bronchial stumps were histologically and immunohistochemically analyzed to assess connective tissue formation, blood vessel formation, and inflammation. RESULTS Fibroblast sheets secreted high levels of pro-healing and pro-angiogenic factors in vitro. No adverse events or serious postoperative complications associated with the fibroblast sheet transplantation were observed. The cell sheet-transplanted group exhibited a layered structure of newly formed tissue around the bronchial stump. This was associated with enhanced blood vessel formation, as indicated by increased CD31-positive cells and high VEGF levels. The untreated control group showed a localized nodule of inflammation near the bronchial stump, which lacked evidence of blood vessel formation. CONCLUSION Autologous multilayered fibroblast sheet transplantation promoted connective tissue formation and blood vessel growth around the bronchial stump after lobectomy in a canine model. These findings suggest that fibroblast sheet transplantation is a promising therapeutic approach for preventing BPF after lung resection.
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Affiliation(s)
- Junichi Murakami
- Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.
- Division of Advanced Cell Therapy, Research Institute for Cell Design Medical Science, Yamaguchi University, Yamaguchi, Japan.
| | - Toshiki Tanaka
- Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Kenji Tani
- Laboratory of Veterinary Surgery, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan
- Division of Translational Research for One Medicine, Research Institute for Cell Design Medical Science, Yamaguchi University, Yamaguchi, Japan
| | - Koji Ueno
- Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
- Division of Advanced Cell Therapy, Research Institute for Cell Design Medical Science, Yamaguchi University, Yamaguchi, Japan
| | - Naohiro Yamamoto
- Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Sota Yoshimine
- Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Melpa Susanti Purba
- Laboratory of Veterinary Surgery, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan
| | - Hiroshi Sunahara
- Laboratory of Veterinary Surgery, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan
| | - Yoshinobu Hoshii
- Department of Diagnostic Pathology, Yamaguchi University Hospital, Yamaguchi, Japan
| | - Kimikazu Hamano
- Department of Surgery and Clinical Science, Division of Chest Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
- Division of Advanced Cell Therapy, Research Institute for Cell Design Medical Science, Yamaguchi University, Yamaguchi, Japan
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25
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Bello ZM, de Azambuja Ribeiro RIM, Dos Santos HB, Thomé RG. Unveiling the therapeutic potential of medicinal plants in zebrafish caudal fin regeneration and wound healing: a systematic review. FISH PHYSIOLOGY AND BIOCHEMISTRY 2025; 51:80. [PMID: 40214856 DOI: 10.1007/s10695-025-01495-x] [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: 01/20/2025] [Accepted: 03/30/2025] [Indexed: 04/19/2025]
Abstract
This systematic review aims to examine the existing literature on the therapeutic potential of medicinal plants to improve caudal fin regeneration and wound healing in zebrafish (Danio rerio), focusing on uncovering their pharmacological properties and potential use in enhancing tissue repair and regeneration. A thorough review of suitable and eligible full-text articles was performed on PubMed, Scopus, Web of Science, and Google Scholar from 1 st January 2014 to 31 st December 2024. These articles were searched using the Medical Subject Headings terms "zebrafish," "zebrafish larvae," "zebrafish embryo," "angiogenesis," "Medicinal plants," "Natural products," "Fin regeneration," "wound healing," and "inflammation." Here, 520 articles on medicinal plants and their potential in caudal fin regeneration and wound healing in zebrafish were identified across the databases searched, of which 26 were included in this study following screening. After thoroughly reviewing the articles, some were found to have used multiple medicinal plants. Thus, 38 medicinal plants were found to have promoted effects on zebrafish caudal fin regeneration and wound healing, and 21 revealed no effects on either caudal fin regeneration and wound healing. This systematic review explores the therapeutic potential of medicinal plants in caudal fin regeneration and wound healing in a zebrafish model. The results show a promising effect of various plant species in enhancing fin regeneration and wound healing. Further research is needed to understand the molecular mechanisms and to translate these findings into clinical applications for human wound healing and regenerative medicine.
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Affiliation(s)
- Zakariyya Muhammad Bello
- Laboratório de Processamento de Tecidos - LAPROTEC, Universidade Federal de São João Del-Rei, Campus Centro Oeste, Rua Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501 - 296, Brazil
| | - Rosy Iara Maciel de Azambuja Ribeiro
- Laboratório de Patologia Experimental - LAPATEX, Universidade Federal de São João Del-Rei, Campus Centro Oeste, Rua Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501 - 296, Brazil
| | - Hélio Batista Dos Santos
- Laboratório de Processamento de Tecidos - LAPROTEC, Universidade Federal de São João Del-Rei, Campus Centro Oeste, Rua Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501 - 296, Brazil
| | - Ralph Gruppi Thomé
- Laboratório de Processamento de Tecidos - LAPROTEC, Universidade Federal de São João Del-Rei, Campus Centro Oeste, Rua Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501 - 296, Brazil.
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26
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Vicente-da-Silva J, Pereira JOSL, do Carmo FA, Patricio BFDC. Skin and Wound Healing: Conventional Dosage versus Nanobased Emulsions Forms. ACS OMEGA 2025; 10:12837-12855. [PMID: 40224422 PMCID: PMC11983225 DOI: 10.1021/acsomega.5c00455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/13/2025] [Accepted: 03/18/2025] [Indexed: 04/15/2025]
Abstract
The skin plays a crucial role in the body's homeostasis through its thermoregulation functions, metabolic activity, and, mainly, its barrier function. Once this system has its homeostasis disturbed, through the promotion of tissue discontinuity, an injury happens and a restoration process starts. Different products can be used to promote, accelerate, or stimulate the healing process, such as hydrogels, emulsions, and ointments (main conventional formulations). Despite the historical use and wide market and consumer acceptance, new systems emerged for wound management with the main challenge to overcome conventional form limitations, in which nanosystems are found, mainly nanobased emulsion forms (nano- and microemulsions, NE and ME). Here, we discuss the skin function and wound healing process, highlighting the cellular and molecular processes, the different wound classifications, and factors that affect physiological healing. We also investigated the recent patents (2012-2023) filed at the United States Patent and Trademark Office, where we found few patents for conventional forms (hydrogels = 5; emulsions = 4; ointments = 6) but a larger number of patents for nanobased emulsions filed in this time (NE = 638; ME = 4,072). Furthermore, we address the use of nanobased emulsions (NE and ME) and their particularities, differences, and application in wound treatment. This work also discusses the challenges, bottlenecks, and regulatory framework for nanosystems, industrial, academic, and government interest in nanotechnology, and future perspectives about this key factor for the nanosystems market and consumer acceptance.
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Affiliation(s)
- João
Vitor Vicente-da-Silva
- PostGraduate
Program in Molecular and Cellular Biology, Department of Physiological
Sciences − Pharmacology, Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-040, Brazil
- Pharmaceutical
and Technological Innovation Laboratory, Department of Physiological
Sciences − Pharmacology, Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-040, Brazil
| | - Juliana Oliveira
da Silva Lopes Pereira
- Pharmaceutical
and Technological Innovation Laboratory, Department of Physiological
Sciences − Pharmacology, Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-040, Brazil
| | - Flávia Almada do Carmo
- Laboratory
of Pharmaceutical Industrial Technology, Department of Drugs and Pharmaceutics,
Faculty of Pharmacy, Federal University
of Rio de Janeiro, Rio de Janeiro 21941-971, Brazil
- PostGraduate
Program in Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-971, Brazil
| | - Beatriz Ferreira de Carvalho Patricio
- PostGraduate
Program in Molecular and Cellular Biology, Department of Physiological
Sciences − Pharmacology, Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-040, Brazil
- Pharmaceutical
and Technological Innovation Laboratory, Department of Physiological
Sciences − Pharmacology, Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20211-040, Brazil
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Alberts A, Bratu AG, Niculescu AG, Grumezescu AM. Collagen-Based Wound Dressings: Innovations, Mechanisms, and Clinical Applications. Gels 2025; 11:271. [PMID: 40277707 PMCID: PMC12026876 DOI: 10.3390/gels11040271] [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: 03/05/2025] [Revised: 03/30/2025] [Accepted: 04/03/2025] [Indexed: 04/26/2025] Open
Abstract
Collagen-based wound dressings have developed as an essential component of contemporary wound care, utilizing collagen's inherent properties to promote healing. This review thoroughly analyzes collagen dressing advances, examining different formulations such as hydrogels, films, and foams that enhance wound care. The important processes by which collagen promotes healing (e.g., promoting angiogenesis, encouraging cell proliferation, and offering structural support) are discussed to clarify its function in tissue regeneration. The effectiveness and adaptability of collagen dressings are demonstrated via clinical applications investigated in acute and chronic wounds. Additionally, commercially accessible collagen-based skin healing treatments are discussed, demonstrating their practical use in healthcare settings. Despite the progress, the study discusses the obstacles and restrictions encountered in producing and adopting collagen-based dressings, such as the difficulties of manufacturing and financial concerns. Finally, the current landscape's insights indicate future research possibilities for collagen dressing optimization, bioactive agent integration, and overcoming existing constraints. This analysis highlights the potential of collagen-based innovations to improve wound treatment methods and patient care.
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Affiliation(s)
- Adina Alberts
- Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Andreea Gabriela Bratu
- Faculty of Chemical Engineering and Biotechnologies, National University of Science and Technology Politehnica Bucharest, Gh. Polizu St. 1-7, 060042 Bucharest, Romania; (A.G.B.); (A.-G.N.)
| | - Adelina-Gabriela Niculescu
- Faculty of Chemical Engineering and Biotechnologies, National University of Science and Technology Politehnica Bucharest, Gh. Polizu St. 1-7, 060042 Bucharest, Romania; (A.G.B.); (A.-G.N.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania
| | - Alexandru Mihai Grumezescu
- Faculty of Chemical Engineering and Biotechnologies, National University of Science and Technology Politehnica Bucharest, Gh. Polizu St. 1-7, 060042 Bucharest, Romania; (A.G.B.); (A.-G.N.)
- Research Institute of the University of Bucharest—ICUB, University of Bucharest, 050657 Bucharest, Romania
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28
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Azizi L, Hausman H, Meyer AK, Wong M, Pajonk F. The Mevalonate Pathway in the Radiation Response of Cancer. Int J Radiat Oncol Biol Phys 2025:S0360-3016(25)00278-0. [PMID: 40194746 DOI: 10.1016/j.ijrobp.2025.03.059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 02/14/2025] [Accepted: 03/19/2025] [Indexed: 04/09/2025]
Abstract
The mevalonate (MVA) pathway plays a critical role in cholesterol biosynthesis, protein prenylation, and metabolic reprogramming, all of which contribute to cancer progression and therapy resistance. Targeting the MVA pathway with statins and other inhibitors has shown promise in preclinical studies; however, clinical outcomes remain controversial, raising concerns about translating these findings into effective treatments. Additionally, the interaction between the MVA pathway and radiation therapy (RT) is not yet fully understood, as RT upregulates the pathway, which can enhance tumor cell survival. This review summarizes the current literature on MVA pathway inhibition in cancer therapy, focusing on its potential to enhance the efficacy of RT. A better understanding of the pathway's role in radiation responses will be essential to translate combination therapies that target this pathway.
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Affiliation(s)
- Linda Azizi
- Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
| | - Hannah Hausman
- Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California
| | - Alexandra K Meyer
- Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California
| | - Matthew Wong
- Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California
| | - Frank Pajonk
- Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California; Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California; Jonsson Comprehensive Cancer Center at University of California, Los Angeles, Los Angeles, California
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29
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Singh P, Easley A, Menchaca KT, Fanniel V, Gomez R, Marquez J, Hill S. Comparative Study of Placental Allografts with Distinct Layer Composition. Int J Mol Sci 2025; 26:3406. [PMID: 40244265 PMCID: PMC11989501 DOI: 10.3390/ijms26073406] [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: 01/30/2025] [Revised: 03/26/2025] [Accepted: 03/31/2025] [Indexed: 04/18/2025] Open
Abstract
Human placental-derived allografts are biomaterials categorized as cellular, acellular, matrix-like products (CAMPs) that can serve as wound coverings due to placenta tissue's innate barrier function. The placental membrane consists of three layers, the amnion, the intermediate layer (IL), and the chorion, each contributing distinct functional and biological properties. This study investigates how variations in layer composition influence the Extracellular Matrix (ECM) and growth factor profiles of placental allografts. We compared Dual Layer (amnion-amnion), Full Thickness (amnion-intermediate-chorion, FT), and a novel four-layer allograft configuration (amnion-intermediate-chorion-amnion, ACA). Histological analyses using hematoxylin and eosin (H&E) and Masson's trichrome staining revealed distinct structural architecture among the three allografts, with FT and ACA exhibiting 4.9 times and 5.7 times greater thickness as compared with the Dual Layer, respectively. Compositional studies revealed different concentrations of key ECM components (collagen, elastin, proteoglycans, hyaluronic acid) and growth factors (ANG-2, EGF, PDGF-AA, VEGF) across allografts. The collagen concentration was two times higher in ACA as compared with the Dual Layer and FT. Additionally, FT and ACA demonstrated higher levels of growth factors and other ECM components, underscoring their biochemical diversity. These findings highlight the fact that the structural and biochemical properties of placental-derived allografts depend on their layer composition. This study underscores the importance of tailoring layer configurations that are optimized for clinical applications of CAMPs, enabling clinicians to select the most suitable grafts for clinical use, such as for wound management.
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Affiliation(s)
| | | | | | | | | | | | - Shauna Hill
- RegenTX Labs LLC, 3463 Magic Dr Ste 315, San Antonio, TX 78229, USA
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30
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You C, Wang C, Ma Z, Yu Q, Liu S. Review on application of silk fibroin hydrogels in the management of wound healing. Int J Biol Macromol 2025; 298:140082. [PMID: 39832605 DOI: 10.1016/j.ijbiomac.2025.140082] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Revised: 01/06/2025] [Accepted: 01/17/2025] [Indexed: 01/22/2025]
Abstract
Wounds are regarded as disruptions in the integrity of human skin tissues, and the process of wound healing is often characterized as protracted and complex, primarily due to the potential infection or inflammation caused by microorganisms. The quest for innovative solutions that accelerate wound healing while prioritizing patient safety and comfort has emerged as a focal point. Within this pursuit, silkworm silk fibroin-a natural polymer extracted from silk cocoons-exhibits a distinctive combination of properties including biocompatibility, biodegradability, superior mechanical strength, water absorption, and low immunogenicity, which align closely with the demands of contemporary wound care. Its remarkable biocompatibility facilitates seamless integration with host tissues, thereby minimizing the risk of rejection or adverse reactions. Furthermore, its intrinsic degradability permits controlled release of therapeutic agents, promoting an optimal microenvironment conducive to healing. This review investigates the multifaceted potential of silk fibroin specifically as a wound dressing material and examines the intricate nuances associated with its application in hydrogels for wound healing, aiming to furnish a thorough overview for both researchers and clinicians. By scrutinizing underlying mechanisms, current applications, and prospective directions, we aspire to cultivate new insights and inspire innovative strategies within this rapidly evolving field.
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Affiliation(s)
- Chang You
- Westa college, Southwest University, Chongqing 400716, China; State Key Laboratory of Resource Insects, Southwest University, Chongqing 400716, China
| | - Changkun Wang
- Westa college, Southwest University, Chongqing 400716, China; State Key Laboratory of Resource Insects, Southwest University, Chongqing 400716, China
| | - Zhenghao Ma
- Westa college, Southwest University, Chongqing 400716, China; State Key Laboratory of Resource Insects, Southwest University, Chongqing 400716, China
| | - Qianhui Yu
- Westa college, Southwest University, Chongqing 400716, China; State Key Laboratory of Resource Insects, Southwest University, Chongqing 400716, China
| | - Shiping Liu
- State Key Laboratory of Resource Insects, Southwest University, Chongqing 400716, China.
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31
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She Y, Wu P, Wan W, Liu H, Liu R, Wang T, Wang M, Shen L, Yang Y, Huang X, Zhang X, Tian Y, Zhang K. Polysaccharides, proteins and DNA based stimulus responsive hydrogels promoting wound healing and repair: A review. Int J Biol Macromol 2025; 304:140961. [PMID: 39952504 DOI: 10.1016/j.ijbiomac.2025.140961] [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: 12/12/2024] [Revised: 02/08/2025] [Accepted: 02/11/2025] [Indexed: 02/17/2025]
Abstract
The healing of various wounds remains a serious challenge in the medical field, hydrogel has high hydrophilicity and biocompatibility due to its unique network structure, which shows a strong advantage in the field of wound healing. Stimulus responsive hydrogels are particularly effective,which can control the material properties according to the external stimulus source, and provide more targeted treatment for different wounds. Here, we review physiological mechanisms of wound healing and the relationship between polysaccharides, proteins and DNA based stimulus responsive hydrogels and wound healing, materials commonly used of polysaccharides, proteins and DNA based stimulus responsive hydrogels, mechanisms of stimulus responsive hydrogels formation and network structure types, common properties of polysaccharides, proteins and DNA based stimulus responsive hydrogels for promoting wound healing and discuss their applications in medicine. Finally, the limitations and application prospects of polysaccharides, proteins and DNA based stimulus responsive hydrogels were discussed and evaluated. The review focuses on the biomedical use of polysaccharides, proteins and DNA based stimulus responsive hydrogels in wound healing and repair, and provides insights for the development of clinical related materials.
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Affiliation(s)
- Yumo She
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, China
| | - Peng Wu
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, China
| | - Wenyu Wan
- Key Laboratory of Immunodermatology, Ministry of Education, Department of Dermatology, The First Hospital of China Medical University, China; Key Laboratory of Immunodermatology, National Health Commission of the People's Republic of China, The First Hospital of China Medical University, China; National and Local Joint Engineering Research Center of Immunodermatological Theranostics, The First Hospital of China Medical University, China
| | - He Liu
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang 110169, China
| | - Ruonan Liu
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang 110169, China
| | - Tingting Wang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, China
| | - Mengyao Wang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, China
| | - Lufan Shen
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, China
| | - Yuanyuan Yang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, China
| | - Xingyong Huang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, China
| | - Xiaoyue Zhang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, China
| | - Ye Tian
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang 110169, China; Foshan Graduate School of Innovation, Northeastern University, Foshan 528300, China.
| | - Kai Zhang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, China; Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, China.
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32
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Chirivì M, Maiullari F, Milan M, Ceraolo MG, Fratini N, Fasciani A, Bousselmi S, Stirm M, Scalera F, Gervaso F, Villa M, Viganò R, Brambilla F, Mauri P, De Falco E, Silvestre DD, Costantini M, Wolf E, Bearzi C, Rizzi R. Mimicking the Dystrophic Cardiac Extracellular Environment through DystroGel. Adv Healthc Mater 2025; 14:e2404251. [PMID: 39962811 PMCID: PMC11973943 DOI: 10.1002/adhm.202404251] [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: 11/27/2024] [Revised: 02/03/2025] [Indexed: 04/08/2025]
Abstract
Advances in understanding the mechanisms behind genetic diseases like Duchenne muscular dystrophy (DMD) underscore the critical role of the extracellular matrix (ECM) composition in disease progression. Effective in vitro models must replicate the intercellular relationships and physicochemical properties of native ECM to fully capture disease-specific characteristics. Although recent biomaterials support the in vitro biofabrication of pathophysiological environments, they often lack disease-specific ECM features. In this study, DystroGel, a hydrogel derived from the cardiac ECM of a porcine DMD model, replicates the distinct molecular composition of dystrophic cardiac tissue for the first time. The findings indicate that the dystrophic ECM matrix exhibits a unique protein profile, impacting cellular processes critical to DMD pathology. This work demonstrates the importance of using a 3D substrate that recreates intercellular dynamics within a defined pathological environment, enhancing the ability to model genetic disorders and providing a valuable tool for advancing personalized therapeutic strategies.
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Affiliation(s)
- Maila Chirivì
- Department of Molecular MedicineSapienza UniversityViale Regina Elena, 324Rome00161Italy
- Neurology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoVia Francesco Sforza, 35Milan20122Italy
| | - Fabio Maiullari
- Ph.D. Program in Cellular and Molecular BiologyDepartment of BiologyUniversity of Rome “Tor Vergata”Via della Ricerca Scientifica, 1Rome00133Italy
| | - Marika Milan
- Neurology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoVia Francesco Sforza, 35Milan20122Italy
| | - Maria Grazia Ceraolo
- Neurology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoVia Francesco Sforza, 35Milan20122Italy
| | - Nicole Fratini
- Department of Molecular MedicineSapienza UniversityViale Regina Elena, 324Rome00161Italy
| | - Alessandra Fasciani
- Fondazione Istituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi”Via Francesco Sforza, 35Milan20122Italy
| | - Salma Bousselmi
- Neurology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoVia Francesco Sforza, 35Milan20122Italy
- Ph.D. Program in Cellular and Molecular BiologyDepartment of BiologyUniversity of Rome “Tor Vergata”Via della Ricerca Scientifica, 1Rome00133Italy
| | - Michael Stirm
- Chair for Molecular Animal Breeding and BiotechnologyGene Center and Department of Veterinary SciencesLMU Munich81377MunichGermany
- Center for Innovative Medical Models (CiMM)Department of Veterinary SciencesLMU Munich85764OberschleißheimGermany
| | - Francesca Scalera
- Institute of NanotechnologyNational Research Councilc/o Campus Ecoteknevia MonteroniLecce73100Italy
| | - Francesca Gervaso
- Institute of NanotechnologyNational Research Councilc/o Campus Ecoteknevia MonteroniLecce73100Italy
| | - Michela Villa
- Fondazione Istituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi”Via Francesco Sforza, 35Milan20122Italy
- Department of BiosciencesUniversity of MilanVia Celoria, 26Milan20133Italy
| | - Raffaello Viganò
- Institute for Biomedical TechnologiesNational Research CouncilVia Fratelli Cervi, 93, SegrateMilan20054Italy
| | - Francesca Brambilla
- Institute for Biomedical TechnologiesNational Research CouncilVia Fratelli Cervi, 93, SegrateMilan20054Italy
| | - Pierluigi Mauri
- Institute for Biomedical TechnologiesNational Research CouncilVia Fratelli Cervi, 93, SegrateMilan20054Italy
| | - Elena De Falco
- Institute for Biomedical TechnologiesNational Research CouncilVia Fratelli Cervi, 93, SegrateMilan20054Italy
| | - Dario Di Silvestre
- Department of BiosciencesUniversity of MilanVia Celoria, 26Milan20133Italy
| | - Marco Costantini
- Institute of Physical Chemistry – Polish Academy of SciencesMarcina Kasprzaka 44/52Warsaw01–224Poland
| | - Eckhard Wolf
- Chair for Molecular Animal Breeding and BiotechnologyGene Center and Department of Veterinary SciencesLMU Munich81377MunichGermany
| | - Claudia Bearzi
- Institute for Biomedical TechnologiesNational Research CouncilVia Fratelli Cervi, 93, SegrateMilan20054Italy
| | - Roberto Rizzi
- Department of Medical‐Surgical Sciences and BiotechnologiesSapienza University of RomeC.so della Repubblica 79Latina04100Italy
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33
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Guo C, Rizkalla AS, Hamilton DW. FGF and TGF-β growth factor isoform modulation of human gingival and periodontal ligament fibroblast wound healing phenotype. Matrix Biol 2025; 136:9-21. [PMID: 39756500 DOI: 10.1016/j.matbio.2024.12.011] [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: 07/25/2024] [Revised: 11/18/2024] [Accepted: 12/26/2024] [Indexed: 01/07/2025]
Abstract
Release of growth factors in the tissue microenvironment is a critical process in the repair and regeneration of periodontal tissues, regulating fibroblast behavior and phenotype. As a result of the complex architecture of the periodontium, distinct fibroblast populations in the periodontal ligament and gingival connective tissue exist in close proximity. Growth factor therapies for periodontal regeneration have gained traction, but quantification of their effects on multiple different fibroblast populations that are required for repair has been poorly investigated. In this study, we examined the effects of TGF-β1, TGF-β3, FGF-2, and FGF-9 on human gingival fibroblasts (hGF) and human periodontal ligament cells (hPDL), as well as the combined effects of TGF-β3 and FGF-2. We show that FGF-2 enhances cell migration while TGF-β1 and TGF-β3 promotes matrix production, and TGF-β1 promotes fibroblast to myofibroblast transition. Interestingly, the combination of TGF-β3 and FGF-2, acting through both p-SMAD3 and p-ERK pathways, mitigates the inhibitory effects of TGF-β3 on migration in hPDL cells, suggesting synergistic and complimentary effects of FGF-2 and TGF-β3. Additionally, fibronectin production in hGF increased when treated with the combined TGF-β3+FGF-2 compared to FGF-2 alone, indicating that the effects of TGF-β3 in promoting extracellular matrix production are still active in the combined treatment condition. Finally, our study highlights that FGF-9 did not influence migration, α-SMA expression, or extracellular matrix production in either cell type, emphasizing the unique roles of specific growth factors in cellular responses. The synergistic effects observed with combined TGF-β3 and FGF-2 treatments present promising avenues for further research and clinical advancements in regenerative medicine.
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Affiliation(s)
- Chengyu Guo
- Department of Anatomy and Cell Biology, Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, N6A 3K7, Canada; Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, N6A 3K7, Canada
| | - Amin S Rizkalla
- Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, N6A 3K7, Canada; Department of Chemical and Biochemical, Thompson Engineering Building, Western University, London, Ontario, N6A 5B9, Canada
| | - Douglas W Hamilton
- Department of Anatomy and Cell Biology, Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, N6A 3K7, Canada; Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, N6A 3K7, Canada.
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34
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Zhang B, Li Y, Wu K, Wei L, Chen Y, Zhang Y, Ren Y, Zou T, Yu P, Ma H, Chen R, Liu X, Cheng Y. Okra juice used for rapid wound healing through its bioadhesive and antioxidant capabilities. Mater Today Bio 2025; 31:101495. [PMID: 39896277 PMCID: PMC11787035 DOI: 10.1016/j.mtbio.2025.101495] [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: 07/30/2024] [Revised: 10/31/2024] [Accepted: 01/12/2025] [Indexed: 02/04/2025] Open
Abstract
Rapid wound healing is of great importance as it plays a crucial role in the body's response to injury or trauma. Biological adhesives are generally easy to apply, allowing for quick and efficient wound closure. In this study, we develop a natural biological adhesive derived from okra juice through a simple and environmentally friendly producing process. The strongest adhesion ability of this bioadhesive to wet tissue was 5.51 kPa, the ability to inhibit 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl radical, superoxide radical, hydroxyl radical, and hydrogen peroxide was 56.58 %, 49.94 %, 53.86 %, and 52.89 %, respectively, and the ability to promote cell proliferation was 181.46 %. The levels of pro-inflammatory tumor necrosis factor alpha (33.17 %) and Interleukin-6 (46.73 %) were significantly reduced. Both in vitro and in vivo evaluations indicate that it can effectively accelerate the healing process by sealing the wound, improving epithelial regeneration and angiogenesis, and alleviating inflammation. In addition, it has improved biocompatibility compared to commercial medical glue. Based on the favorable properties of the natural source, simple production process, and inherent nontoxicity, it shows potential as a medical bioadhesive for surgical procedures and emergency wound treatment.
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Affiliation(s)
- Biao Zhang
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Yuanqiang Li
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Kaijie Wu
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Liqi Wei
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Yining Chen
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Yuan Zhang
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Yiping Ren
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Tianshu Zou
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Pengcheng Yu
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun, 130022, PR China
| | - Hongxia Ma
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Rui Chen
- Jilin Provincial Key Laboratory of Human Health Status Identification and Function Enhancement, School of Materials Science and Engineering, Changchun University, Changchun, 130022, PR China
| | - Xin Liu
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
| | - Yan Cheng
- Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, College of Life Science, Jilin Agricultural University, Changchun, 130118, PR China
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35
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Xiong S, Ding X, Zhou L, Liu Z, Jiang W, Ai F, Cai K. An antibacterial and antioxidant rosmarinic acid hydrogel normalizes macrophage polarization to expedite diabetic wound healing. J Colloid Interface Sci 2025; 683:357-371. [PMID: 39736166 DOI: 10.1016/j.jcis.2024.12.138] [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: 09/22/2024] [Revised: 12/17/2024] [Accepted: 12/18/2024] [Indexed: 01/01/2025]
Abstract
The management of diabetic wounds (DW) is a significant challenge within the medical field. Effectively regulating the levels of reactive oxygen species (ROS) at the wound site and orchestrating the inflammatory response are effective strategies for DW treatment. In this study, a novel hydrogel was developed by cross-linking polyboronic acid-modified carboxymethyl chitosan with herbal active ingredient rosmarinic acid (RA), an active herbal ingredient, through dynamic boronic esters formation. In this RA hydrogel (RAgel), RA serves both as an active pharmaceutical ingredient and as a linker for the creation of a dynamic covalent hydrogel, which can decrease the potential toxicity of chemical crosslinking agents and improve the utilization of RA. RAgel demonstrated potential for controlling RA loading and responsiveness to ROS and glucose levels in a diabetic wound environment. Additionally, the intrinsic antioxidant and antibacterial properties of RA were effectively preserved and enhanced upon integration into RAgel. Furthermore, RAgel not only promoted the migration of L929 cells, a key aspect of tissue repair, but also induced M2 polarization in macrophages,while inhibiting the secretion of pro-inflammatory cytokines. In a murine model of diabetic wound healing, RAgel significantly enhanced the proliferation of both the epidermal and granulation tissues. It also exerts a marked anti-inflammatory effect and promotes collagen deposition, thereby expediting the overall wound healing process. The reported RAgel formulation has potential to address the complex challenges associated with diabetic wound management.
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Affiliation(s)
- Shiyu Xiong
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China
| | - Xingwei Ding
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China.
| | - Ling Zhou
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China
| | - Ziqian Liu
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China
| | - Wenyan Jiang
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China
| | - Fanrong Ai
- School of Advanced Manufacturing, Nanchang University, Nanchang, Jiangxi 330031, PR China.
| | - Kaiyong Cai
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
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36
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Benito‐Martínez S, Pérez‐Köhler B, Rodríguez M, Rivas‐Santos C, María Izco J, Recalde JI, Pascual G. Assessing New Collagen Therapies for Wound Healing: A Murine Model Approach. Int Wound J 2025; 22:e70589. [PMID: 40258681 PMCID: PMC12011449 DOI: 10.1111/iwj.70589] [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: 09/06/2024] [Revised: 03/24/2025] [Accepted: 04/10/2025] [Indexed: 04/23/2025] Open
Abstract
Collagen proteins play important roles in wound healing and are of great interest in regenerative medicine. This study evaluated the efficacy of new collagen-based products and compared them to commercial products in a murine model of cutaneous healing. Circular excisional defects were generated on 72 Wistar rats. Six study groups were established according to the administered collagen treatment: Control (without treatment), SD-C (semidenatured), Catrix, Hy-C (hydrolyzed), N-C (native) and Helix3-CP. Seven and eighteen days post-surgery, animals were euthanized. Wound closure was macroscopically assessed by taking zenithal images of the defects. Morphological, histological and immunohistochemical studies were performed to evaluate the healing process. After 7 days, open areas and degree of epithelialization were similar among the groups. Significant differences were observed in contraction between control and the N-C and Helix3-CP groups. Untreated animals exhibited a more pronounced granulation tissue with a high number of inflammatory cells and a disorganised extracellular matrix with type III collagen deposition. After 18 days, animals treated with new collagen (Hy-C and N-C) exhibited accelerated wound closure, increased epithelialization and a more organised granulation tissue. Local administration of new collagen treatments promotes the progression of the reparative process and significantly accelerates wound closure compared with nontreated wounds.
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Affiliation(s)
- Selma Benito‐Martínez
- Departamento de Medicina y Especialidades Médicas, Facultad de Medicina y Ciencias de la SaludUniversidad de AlcaláAlcalá de HenaresMadridSpain
- Biomedical Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER‐BBN)MadridSpain
- Ramón y Cajal Health Research Institute (IRYCIS)MadridSpain
| | - Bárbara Pérez‐Köhler
- Departamento de Medicina y Especialidades Médicas, Facultad de Medicina y Ciencias de la SaludUniversidad de AlcaláAlcalá de HenaresMadridSpain
- Biomedical Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER‐BBN)MadridSpain
- Ramón y Cajal Health Research Institute (IRYCIS)MadridSpain
| | - Marta Rodríguez
- Biomedical Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER‐BBN)MadridSpain
- Ramón y Cajal Health Research Institute (IRYCIS)MadridSpain
- Departamento de Cirugía, Ciencias Médicas y Sociales, Facultad de Medicina y Ciencias de la SaludUniversidad de AlcaláAlcalá de HenaresMadridSpain
| | - Celia Rivas‐Santos
- Departamento de Medicina y Especialidades Médicas, Facultad de Medicina y Ciencias de la SaludUniversidad de AlcaláAlcalá de HenaresMadridSpain
- Ramón y Cajal Health Research Institute (IRYCIS)MadridSpain
| | | | | | - Gemma Pascual
- Departamento de Medicina y Especialidades Médicas, Facultad de Medicina y Ciencias de la SaludUniversidad de AlcaláAlcalá de HenaresMadridSpain
- Biomedical Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER‐BBN)MadridSpain
- Ramón y Cajal Health Research Institute (IRYCIS)MadridSpain
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Khalpey Z, Kumar UA, Hitscherich P, Khalpey Z, Phillips T, Chnari E, Long M. Implementation of Aseptically Processed Human Placental Membrane Allografts Within a Comprehensive Sternal Wound Closure Strategy: A Three-Phase Experience. J Clin Med 2025; 14:1877. [PMID: 40142685 PMCID: PMC11942933 DOI: 10.3390/jcm14061877] [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: 02/02/2025] [Revised: 03/07/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Background: Sternal wound complications following median sternotomy result in poor outcomes. Novel approaches such as placental allografts are being explored to optimize wound closure. Methods: This study evaluated consecutive patients undergoing median sternotomy by a single surgeon as sternal closure strategies evolved. Initially, wires with autologous platelet-rich plasma (PRP) were used (Group 1). Subsequently, suture tapes with PRP and an aseptically processed amnion-chorion placental allograft (aACPA) were added (Group 2). Finally, PRP was discontinued (Group 3). Sternal infection, dehiscence, pain outcomes, hospital length of stay, and patient risk factors were analyzed. Results: Compared to Group 1, Groups 2 and 3 demonstrated significantly lower infection (0.7%, 0% vs. 9.3%, p = 0.0001) and dehiscence rates (0%, 0% vs. 8.7%, p < 0.0001). Significant postoperative pain at two weeks decreased from Group 1 to Groups 2 and 3 (18.7%, 4.7%, 3.1%, p < 0.0001), with similar improvements at one month (12.0%, 2.0%, 1.5%, p = 0.0005). Despite higher median risk factors in Group 3 than in Groups 1 and 2 (3 vs. 2, 2, p = 0.0305), a trend toward reduced hospital stay was observed (6 vs. 8, 7 days, p = 0.2298). Conclusions: Adding aACPA to sternal closure significantly reduced infections, dehiscence, and pain in high-risk cardiac surgery patients, with sustained benefits and no increase in operative times. These findings highlight aACPA's potential to mitigate sternal complications, warranting further study in larger cohorts.
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Affiliation(s)
- Zain Khalpey
- Department of Cardiac Surgery, HonorHealth, Suite 300, 10210 N 92nd St., Scottsdale, AZ 85258, USA;
- Khalpey AI Lab, Applied & Translational AI Research Institute (ATARI), 10210 N 92nd St., Scottsdale, AZ 85258, USA;
| | - Ujjawal Aditya Kumar
- Department of Cardiac Surgery, HonorHealth, Suite 300, 10210 N 92nd St., Scottsdale, AZ 85258, USA;
- Khalpey AI Lab, Applied & Translational AI Research Institute (ATARI), 10210 N 92nd St., Scottsdale, AZ 85258, USA;
- School of Clinical Medicine, University of Cambridge, Hills Road, Cambridge CB2 0SP, UK
| | - Pamela Hitscherich
- Department of Research & Development, MTF Biologics, Edison, NJ 08837, USA; (P.H.); (E.C.); (M.L.)
| | - Zacharya Khalpey
- Khalpey AI Lab, Applied & Translational AI Research Institute (ATARI), 10210 N 92nd St., Scottsdale, AZ 85258, USA;
| | - Tyler Phillips
- Department of Cardiac Surgery, HonorHealth, Suite 300, 10210 N 92nd St., Scottsdale, AZ 85258, USA;
- Khalpey AI Lab, Applied & Translational AI Research Institute (ATARI), 10210 N 92nd St., Scottsdale, AZ 85258, USA;
| | - Evangelia Chnari
- Department of Research & Development, MTF Biologics, Edison, NJ 08837, USA; (P.H.); (E.C.); (M.L.)
| | - Marc Long
- Department of Research & Development, MTF Biologics, Edison, NJ 08837, USA; (P.H.); (E.C.); (M.L.)
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Johnson CR, Schoenfisch MH. Photoinitiated Nitric Oxide Release as an Antibacterial Treatment for Chronic Wounds. ACS Biomater Sci Eng 2025; 11:1510-1522. [PMID: 39933146 DOI: 10.1021/acsbiomaterials.4c01955] [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: 02/13/2025]
Abstract
Taking advantage of their innate roles as antibacterial strategies, the dual activity of photobiomodulation (PBM) and nitric oxide (NO) was combined to provide a tunable, on-demand chronic wound therapeutic. S-nitrosothiol-modified mesoporous silica nanoparticles (RSNO-MSNs) were doped into polyurethane (PU) to demonstrate preliminary utility as an antibacterial wound dressing treatment for chronic wounds. Photoinitiated and resultant NO-release kinetics and payloads were evaluated at 405, 430, and 530 nm for multiple irradiances. The use of photons and the NO-releasing MSNs against common chronic wound pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, proved to be highly bactericidal. Cytocompatibility of the treatment was confirmed using human epidermal keratinocytes, a representative skin cell line.
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Affiliation(s)
- Courtney R Johnson
- Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Mark H Schoenfisch
- Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
- Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
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Carver A, Choong M, Fawdry R, Boylan CT, Nanavati N. Do operative or weight-bearing delays lead to worse outcomes in ankle surgery? Foot (Edinb) 2025; 62:102159. [PMID: 40203477 DOI: 10.1016/j.foot.2025.102159] [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: 01/28/2025] [Revised: 03/18/2025] [Accepted: 03/23/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Ankle fractures comprise 10 % of fractures seen in ED. Despite this, debate remains regarding the optimal timing of surgery and weight bearing post-operatively. There is no clear consensus whether delaying ankle ORIF leads to better outcomes. There is also debate whether early post-operative weight bearing (WB) impacts post-operative outcomes. The aim of this study was to investigate whether a delay in operation or a prolonged post-operative weight-bearing plan led to (1) increased complications and (2) poorer outcomes in patient-recorded outcome measures (PROMs). METHODS In this retrospective study, 160 patients were analysed. Primary outcomes were post-operative complications. Secondary outcomes were PROMs, using EQ-5D and MOxFQ questionnaires. Data was analysed using SPSS26. Analysis used independent two-tailed Mann-Whitney U tests for continuous data with nominal independent variables, and Kruskal-Wallace tests for ordinal independent variables. Fisher-exact tests were used for categorical variables. RESULTS Delay in operation had no statistically significant impact on overall complication rate (p = 0.482). There was no statistically significant difference in EQ-5D (p = 0.433) and MOxFQ (p = 0.325) scores regardless of delay in operation. Additionally, time spent until WB post-operatively had no statistically significant impact on overall complication rate (p = 0.634). There was no statistically significant difference in EQ-5D (p = 0.358) and MOxFQ (p = 0.089) scores regardless of post-operative WB plan. CONCLUSIONS/FINDINGS Our results suggest that a delay in ankle ORIF operation does not lead to an increase in complications or poorer PROMs post-operatively, endorsing GIRFT principles. Early post-operative WB also had no impact on complication rate or PROMs, meaning early mobilisation may accelerate patient rehabilitation, facilitate independence, and reduce prolonged inpatient hospital stay.
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Affiliation(s)
- Alexander Carver
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; The Rotherham NHS Foundation Trust, Rotherham, UK.
| | - Marc Choong
- The Rotherham NHS Foundation Trust, Rotherham, UK
| | - Robert Fawdry
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; The Rotherham NHS Foundation Trust, Rotherham, UK
| | - Conor T Boylan
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
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Tasdurmazli S, Cinar I, Karamese M, Aksak Karamese S, Cadirci E, Melo LDR, Ozbek T. Exploring in vitro efficacy of rCHAPk with antibiotic combinations, and promising findings of its therapeutic potential for clinical-originated MRSA wound infection. Int J Biol Macromol 2025; 296:139630. [PMID: 39788229 DOI: 10.1016/j.ijbiomac.2025.139630] [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: 06/02/2024] [Revised: 12/24/2024] [Accepted: 01/06/2025] [Indexed: 01/12/2025]
Abstract
The increasing threat of antimicrobial-resistant bacteria, particularly Staphylococcus aureus, which rapidly develops multidrug resistance and commonly colonizes wound surfaces, demands innovative strategies. Phage-encoded endolysins offer a dual-purpose approach as topical therapies for infectious skin wounds and synergistic agents to reduce high-dose antibiotic dependence. This study explores recombinant CHAPk (rCHAPk), efficiently synthesized within 3 h, displaying broad-spectrum antibacterial activity against 10 Gram-positive strains, including resistant variants, with rapid bactericidal kinetics. Application of 10 μg of rCHAPk reduced OD600 by 0.4 within 5 min against a clinical methicillin-resistant S. aureus (MRSA) strain. Combining rCHAPk (1.875 μg/mL) with oxacillin/vancomycin lowered their minimum bactericidal concentrations to 1 μg/mL from initial values over 64 μg/mL and 32 μg/mL, respectively, with a fractional inhibitory concentration index below 0.1. rCHAPk retained efficacy after one year of refrigerated storage. In in vivo experiments, rCHAPk outperformed commercial fucidin therapy in MRSA-induced murine wound models over two weeks, enhancing wound healing by modulating pro-inflammatory cytokine responses and the proliferative phase. This study, for the first time, investigates rCHAPk's in vitro combination with antibiotics and wound healing parameters, highlighting its potential as a potent antibacterial agent synergizing with antibiotics to address antibiotic-resistant bacterial wound infections.
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Affiliation(s)
- Semra Tasdurmazli
- Yıldız Technical University, Faculty of Science and Arts, Department of Molecular Biology and Genetics, Istanbul, Turkey
| | - Irfan Cinar
- Kastamonu University, Faculty of Medicine, Kastamonu, Turkey
| | | | | | - Elif Cadirci
- Ataturk University, Faculty of Medicine, Erzurum, Turkey
| | - Luís D R Melo
- Center of Biological Engineering, University of Minho, 4710-057 Braga, Portugal; LABBELS -Associate Laboratory, Braga, Guimarães, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Tulin Ozbek
- Yıldız Technical University, Faculty of Science and Arts, Department of Molecular Biology and Genetics, Istanbul, Turkey.
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van den Berg R, Visscher L, Menon AG, Deerenberg EB, Tanis PJ. Suture Techniques and Materials for Fascial Closure of Abdominal Wall Incisions: A Comprehensive Meta-Analysis. ANNALS OF SURGERY OPEN 2025; 6:e548. [PMID: 40134474 PMCID: PMC11932593 DOI: 10.1097/as9.0000000000000548] [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: 08/10/2024] [Accepted: 12/31/2024] [Indexed: 03/27/2025] Open
Abstract
Background The aim of this systematic review and meta-analysis was to evaluate the effectiveness of different suture materials and techniques for laparotomy closure. Methods A literature search was conducted in 3 databases in April 2024. All randomized controlled trials (RCTs) and prospective cohort studies on laparotomy closure were included. The quality of the studies was evaluated using critical appraisal checklists (ROB2 and ROBINS-I). The primary outcome was incisional hernia (IH) formation, and secondary outcomes were fascial dehiscence (FD), combined FD+IH, and surgical site infection (SSI). Meta-analyses were performed using random effects models. Results A total of 41 RCTs and 9 prospective cohort studies were included. Meta-analysis revealed no superiority of slowly absorbable sutures over fast-absorbable sutures (5 studies, 1177 patients). Furthermore, no differences between interrupted and continuous suturing were found (14 studies, 5939 patients). Small-bites technique with a slowly absorbable suture was associated with significantly less risk of IH (odds ratio [OR]: 0.44; 95% confidence interval [CI]: 0.30-0.65), combined FD+IH (OR: 0.40; 95% CI: 0.21-0.75), and SSI (OR: 0.70; 95% CI: 0.53-0.91) compared with a large-bites technique (8 studies, 2360 patients). Significant improvements were found for the continuous modified Smead-Jones suturing in the emergency setting (2 studies, 90 patients) and retention-line suturing (1 RCT, 124 patients). Layered closure (6 studies, 2660 patients) or Hughes closure (2 studies, 772 patients) revealed no superiority over mass closure. Conclusions Closure of laparotomies in the elective setting using a small-bites technique with slowly absorbable sutures is superior over a large-bites technique. More evidence is needed in the emergency setting, with promising alternatives such as the modified Smead-Jones technique and retention-line suturing.
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Affiliation(s)
- Rudolf van den Berg
- From the Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Lucas Visscher
- From the Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Anand G. Menon
- Department of Surgery, IJsselland Hospital, Capelle aan den IJssel, The Netherlands
| | - Eva B. Deerenberg
- Department of General Surgery, Franciscus Gasthus and Vlietland, Rotterdam, The Netherlands
| | - Pieter J. Tanis
- From the Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
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Sari BR, Yesilot S, Ozmen O, Aydin Acar C. Superior In Vivo Wound-Healing Activity of Biosynthesized Silver Nanoparticles with Nepeta cataria (Catnip) on Excision Wound Model in Rat. Biol Trace Elem Res 2025; 203:1502-1517. [PMID: 38865065 PMCID: PMC11872767 DOI: 10.1007/s12011-024-04268-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 06/06/2024] [Indexed: 06/13/2024]
Abstract
Silver nanoparticles were biosynthesized with Nepeta cataria plant extract. It was determined that the synthesized Nc-AgNPs gave a strong absorbance peak at 438 nm wavelength in the UV-vis spectrophotometer. SEM and TEM analyses of Nc-AgNPs showed that the synthesized nanoparticles had a spherical morphology. Based on XRD analysis, the average crystallite size of Nc-AgNPs was calculated at 15.74 nm. At the same time, EDS spectrum analysis exhibited dominant emission energy at 3 keV, indicative of Nc-AgNPs. Nc-AgNPs showed an inhibition zone of 12 nm in gram-negative Escherichia coli, 10 nm in gram-positive Enterococcus faecalis, and 11 nm in Staphylococcus aureus. Nc-AgNPs showed high antioxidant properties, with 63% at 5000 μg/mL. The wound-healing properties of Nc-AgNPs were evaluated in vivo in wound models created in a total of 20 Wistar albino male rats, divided into four groups. After 10 days of treatment, the highest wound closure rate was seen in the Nc-AgNP + Vaseline (Group IV) treatment group, at 94%. It was observed that Nc-AgNP + Vaseline nanoformulation significantly increased wound healing, similar to Silverdin®, and Vaseline alone supported healing but did not result in complete closure. Histopathological examination revealed an increase in mature Type 1 collagen in Group IV and positive control (Group II), with better collagen maturation in vehicle control (Group III) compared to negative control (Group I). Immunohistochemical analysis showed complete epithelialization in Group IV and Group II, with distinct cytokeratin expressions, while Group III exhibited mild expressions.
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Affiliation(s)
- Berfin Rumeysa Sari
- Department of Health and Biomedical Sciences, Burdur Mehmet Akif Ersoy University, Burdur, Turkey
| | - Sukriye Yesilot
- Department of Health and Biomedical Sciences, Burdur Mehmet Akif Ersoy University, Burdur, Turkey
- Department of Nursing, Bucak School of Health, Burdur Mehmet Akif Ersoy University, Burdur, Turkey
| | - Ozlem Ozmen
- Veterinary Faculty, Department of Pathology, Burdur Mehmet Akif Ersoy University, Burdur, Turkey
| | - Cigdem Aydin Acar
- Department of Health and Biomedical Sciences, Burdur Mehmet Akif Ersoy University, Burdur, Turkey.
- Department of Nursing, Bucak School of Health, Burdur Mehmet Akif Ersoy University, Burdur, Turkey.
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Bahadoran Z, Mirmiran P, Hosseinpanah F, Kashfi K, Ghasemi A. Nitric oxide-based treatments improve wound healing associated with diabetes mellitus. Med Gas Res 2025; 15:23-35. [PMID: 39436167 PMCID: PMC11515056 DOI: 10.4103/mgr.medgasres-d-24-00020] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/16/2024] [Accepted: 06/27/2024] [Indexed: 10/23/2024] Open
Abstract
Non-healing wounds are long-term complications of diabetes mellitus (DM) that increase mortality risk and amputation-related disability and decrease the quality of life. Nitric oxide (NO·)-based treatments (i.e., use of both systemic and topical NO· donors, NO· precursors, and NO· inducers) have received more attention as complementary approaches in treatments of DM wounds. Here, we aimed to highlight the potential benefits of NO·-based treatments on DM wounds through a literature review of experimental and clinical evidence. Various topical NO·-based treatments have been used. In rodents, topical NO·-based therapy facilitates wound healing, manifested as an increased healing rate and a decreased half-closure time. The wound healing effect of NO·-based treatments is attributed to increasing local blood flow, angiogenesis induction, collagen synthesis and deposition, re-epithelization, anti-inflammatory and anti-oxidative properties, and potent broad-spectrum antibacterial effects. The existing literature lacks human clinical evidence on the safety and efficacy of NO·-based treatments for DM wounds. Translating experimental favors of NO·-based treatments of DM wounds into human clinical practice needs conducting clinical trials with well-predefined effect sizes, i.e., wound reduction area, rate of wound healing, and hospital length of stay.
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Affiliation(s)
- Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farhad Hosseinpanah
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Khosrow Kashfi
- Department of Molecular, Cellular, and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY, USA
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Beltrán‐Hernández NE, Cardenas L, Jimenez‐Jacinto V, Vega‐Alvarado L, Rivera HM. Biological Activity of Biomarkers Associated With Metastasis in Osteosarcoma Cell Lines. Cancer Med 2025; 14:e70391. [PMID: 40079158 PMCID: PMC11904427 DOI: 10.1002/cam4.70391] [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: 05/03/2024] [Revised: 08/26/2024] [Accepted: 10/20/2024] [Indexed: 03/14/2025] Open
Abstract
INTRODUCTION Osteosarcoma, a highly aggressive bone cancer primarily affecting children and young adults, remains a significant challenge in clinical oncology. Metastasis stands as the primary cause of mortality in osteosarcoma patients. However, the mechanisms driving this process remain incompletely understood. Clarifying the molecular pathways involved in metastasis is essential for enhancing patient prognoses and facilitating the development of targeted therapeutic strategies. METHODS RNA sequencing (RNA-Seq) analysis was employed to compare three conditions, hFOB1.19 versus Saos-2, hFOB1.19 versus SJSA-1, and Saos-2 versus SJSA-1, involving non-cancer osteoblasts (hFOB1.19) and highly metastatic osteosarcoma cell lines (Saos-2 and SJSA-1). Additionally, ENA datasets of RNA-Seq from osteosarcoma biopsies were included. Differentially expressed genes (DEGs) were identified and analyzed through enrichment pathway analysis and protein-protein interaction (PPI) networks. Additionally, for gene candidates, a biochemical evaluation was performed. RESULTS DEGs associated with biological functions pertinent to migration, invasion, and metastasis in osteosarcoma were identified. Notably, matrix metalloproteinase-2 (MMP-2) emerged as a promising candidate. Both canonical or full-length (FL-mmp-2) and N-terminal truncated (NTT-mmp-2) isoforms were discerned in biopsies. Moreover, MMP-2's activity was characterized in cell lines. Additionally, mRNA expression of voltage-gated sodium channels (NaVs) and voltage-gated potassium channels (KVs) was detected, and their functional expression was validated using patch clamp techniques. Evaluation of cell line migration and invasion capacities revealed their reduction in the presence of ion channel blockers (TTX and TEA) and MMP inhibitor (GM6001). CONCLUSIONS The gene functional enrichment analysis of DEGs enabled the identification of interaction networks in osteosarcoma, thereby revealing potential biomarkers. Moreover, the elucidated co-participation of TTX-sensitive NaVs and MMP-2 in facilitating migration and invasion suggests their suitability as novel prognostic biomarkers for osteosarcoma. Additionally, this study introduces a model delineating the potential interaction mechanism among ion channels, MMP-2, and other crucial factors in the metastatic cascade of osteosarcoma.
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Affiliation(s)
| | - Luis Cardenas
- Departamento de Biología Molecular de Plantas, Instituto de Biotecnología, Universidad Nacional Autónoma de MéxicoCuernavacaMorelosMexico
| | - Verónica Jimenez‐Jacinto
- Unidad Universitaria de Secuenciación Masiva y Bioinformática, Instituto de Biotecnología, Universidad Nacional Autónoma de MéxicoCuernavacaMorelosMexico
| | - Leticia Vega‐Alvarado
- Instituto de Ciencias Aplicadas y Tecnología, Universidad Nacional Autónoma de MéxicoCoyoacán Ciudad de MéxicoMexico
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Rodríguez-Moreno M, Legaz I. Molecular Insights into the Interaction of Cathepsin D and Iron in Chronic Wound Healing: Exploring Therapeutic Potential and Mechanisms. Biomedicines 2025; 13:544. [PMID: 40149522 PMCID: PMC11940264 DOI: 10.3390/biomedicines13030544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 02/13/2025] [Accepted: 02/19/2025] [Indexed: 03/29/2025] Open
Abstract
Background: Chronic wounds, such as diabetic ulcers, often fail to progress through healing due to persistent inflammation, infections, and extracellular matrix (ECM) imbalances. Cathepsin D, an aspartate protease active in acidic environments, plays a pivotal role in wound healing by mediating inflammatory responses, ECM remodeling, and macrophage phenotype transitions. Its dysregulation, however, can impair healing, highlighting the need for targeted modulation of its activity. The aim of this study was to investigate the molecular interaction between Fe2+ and cathepsin D's catalytic core and ionic zipper under physiological and acidic conditions to identify strategies to enhance tissue repair and accelerate the healing of chronic wounds. Methods: The molecular structure of active cathepsin D was obtained from the Protein Data Bank (PDB) and analyzed using UCSF Chimera. Molecular interactions between cathepsin D and ferrous ions (Fe2+) were studied, focusing on key residues (D33 and D231) and ionic zipper residues (E5, E180, and D187). Results: Our results showed that the active form of cathepsin D, a 96 kDa dimer, consisted of heterodimers with distinct amino acid chains, where residues D33 and D231 formed the active site, and E5, E180, and D187 constituted the ionic zipper. A functional pocket containing the conserved residues D33 and D231, essential for proteolytic activity, was identified. At physiological pH (~7.5), D33 exhibited the most potent interactions with Fe2+, with interaction energies of -7 × 1017 J at oxygen atoms of the carboxylate group (OD1) and α-carbon (CA) atoms, whereas D231 showed slightly lower energies of -6 × 1017 J at γ-carbon atom (CG) and CA atoms. At acidic pH (~4), E5 was the primary interacting residue, with the shortest distance to Fe2+ (2.69 Å), and showed stable interactions across several atoms, emphasizing its role in metal binding. Conclusions: pH conditions strongly influence the interaction of cathepsin D with Fe2. At physiological pH, residues D33 and D231 demonstrate robust and energetically efficient binding with Fe2+. At the same time, under acidic conditions, E5 emerges as the primary residue involved, potentially affecting the ionic zipper of cathepsin D. These insights provide a molecular foundation for targeting specific residues to modulate cathepsin D activity, presenting promising opportunities for therapeutic strategies aimed at improving chronic wound healing.
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Affiliation(s)
| | - Isabel Legaz
- Department of Legal and Forensic Medicine, Biomedical Research Institute of Murcia (IMIB), Regional Campus of International Excellence “Campus Mare Nostrum”, Faculty of Medicine, University of Murcia (UMU), 30100 Murcia, Spain;
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Duan Y, Li L, Hu J, Zheng B, He K. Engineering Gas-Releasing Nanomaterials for Efficient Wound Healing. Chembiochem 2025; 26:e202400790. [PMID: 39592412 DOI: 10.1002/cbic.202400790] [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: 09/26/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 11/28/2024]
Abstract
The escalating prevalence of tissue damage and its associated complications has elicited global apprehension. While nanomaterial-based wound healing exhibits significant potential in terms of curbing infections and surpassing conventional methods, unresolved concerns regarding nanomaterial controllability and precision remain unresolved, jeopardizing its practical applications. In recent years, a unique strategy for creating gas-releasing nanomaterials for wound repair has been proposed, involving the creation of gas-releasing nanomaterials to facilitate wound repair by generating gas donor moieties. The operational spatiotemporal responsiveness and broad-spectrum antibacterial properties of these gases, combined with their inability to generate bacterial resistance like traditional antibiotics, establish their efficacy in addressing chronic non-healing wounds, specifically diabetic foot ulcers (DFUs). In this review, we delve into the intricacies of wound healing process, emphasizing the chemical design, functionality, bactericidal activity, and potential of gas-release materials, encompassing NO, CO, H2S, O2, CO2, and H2, for effective wound healing. Furthermore, we explore the advancements in synergistic therapy utilizing these gases, aiming to enhance our overall comprehension of this field. The insights gleaned from this review will undoubtedly aid researchers and developers in the creation of promising gas-releasing nanomaterials, thus propelling efficient wound healing in the future.
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Affiliation(s)
- Yutian Duan
- SINOPEC Nanjing Research Institute of Chemical Industry Co., Ltd., Nanjing, 210048, China
| | - Lei Li
- China Petroleum & Chemical Corporation, Beijing, 100728, China
| | - Jinming Hu
- Hefei National Research Center for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026, China
| | - Bin Zheng
- School of Chemistry and Pharmaceutical Engineering, Hefei Normal University, Hefei, Anhui, 230061, China
| | - Kewu He
- Imaging Center of the Third Affiliated Hospital of Anhui Medical University, Hefei, 230031, Anhui, China
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Zhao Y, Chen Z, Xie S, Xiao F, Hu Q, Ju Z. The emerging role and therapeutical implications of ferroptosis in wound healing. BURNS & TRAUMA 2025; 13:tkae082. [PMID: 39958433 PMCID: PMC11827611 DOI: 10.1093/burnst/tkae082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 11/11/2024] [Accepted: 12/03/2024] [Indexed: 02/18/2025]
Abstract
Wound healing is a complex biological process involving multiple steps, including hemostasis, inflammation, proliferation, and remodeling. A novel form of regulated cell death, ferroptosis, has garnered attention because of its involvement in these processes. Ferroptosis is characterized by the accumulation of lipid peroxides and is tightly regulated by lipid metabolism, iron metabolism, and the lipid-peroxide repair network, all of which exert a significant influence on wound healing. This review highlights the current findings and emerging concepts regarding the multifaceted roles of ferroptosis throughout the stages of normal and chronic wound healing. Additionally, the potential of targeted interventions aimed at modulating ferroptosis to improve wound-healing outcomes is discussed.
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Affiliation(s)
- Yanan Zhao
- Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, No. 601, Huangpu Avenue West, Tianhe District, Guangzhou, 510632, China
| | - Zhiyang Chen
- Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, No. 601, Huangpu Avenue West, Tianhe District, Guangzhou, 510632, China
| | - Shenghao Xie
- Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, No. 601, Huangpu Avenue West, Tianhe District, Guangzhou, 510632, China
| | - Feng Xiao
- Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, No. 601, Huangpu Avenue West, Tianhe District, Guangzhou, 510632, China
| | - Qian Hu
- Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, No. 601, Huangpu Avenue West, Tianhe District, Guangzhou, 510632, China
| | - Zhenyu Ju
- Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, No. 601, Huangpu Avenue West, Tianhe District, Guangzhou, 510632, China
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Morabbi A, Karimian M. Therapeutic potential of exosomal lncRNAs derived from stem cells in wound healing: focusing on mesenchymal stem cells. Stem Cell Res Ther 2025; 16:62. [PMID: 39934913 PMCID: PMC11816792 DOI: 10.1186/s13287-025-04200-0] [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: 07/12/2024] [Accepted: 01/30/2025] [Indexed: 02/13/2025] Open
Abstract
The self-renewal ability and multipotency of stem cells give them great potential for use in wound healing. Stem cell-derived exosomes, owing to their close biological resemblance to their parent cells, offer a more efficient, safer, and economical approach for facilitating cellular communication and interactions within different environments. This potential makes them particularly valuable in the treatment of both acute and chronic wounds, such as lacerations, burns, and diabetic ulcers. Long non-coding RNAs (lncRNAs) enclosed in exosomes, as one of the leading actors of these extracellular microvesicles, through interaction with miRNAs and regulation of various signaling pathways involved in inflammation, angiogenesis, cell proliferation, and migration, could heal the wounds. Exosome-derived lncRNAs from stem cells facilitate extracellular matrix remodeling through interaction between macrophages and fibroblasts. Moreover, alongside regulating the expression of inflammatory cytokines, controlling reactive oxygen species levels, and enhancing autophagic activity, they also modulate immune responses to support wound healing. Regulating the expression of genes and signaling pathways related to angiogenesis, by increasing blood supply and accelerating the delivery of essential substances to the wound environment, is another effect exosomal lncRNAs derived from stem cells for wound healing. These lncRNAs can also enhance skin wound healing by regulating homeostasis, increasing the proliferation and differentiation of cells involved in the wound-healing process, and enhancing fibroblast viability and migration to the injury site. Ultimately, exosome-derived lncRNAs from stem cells offer valuable and novel insights into the molecular mechanisms underlying improved wound healing. They can pave the way for potential therapeutic strategies, fostering further research for a better future. Meanwhile, exosomes derived from mesenchymal stem cells, due to their exceptional regenerative properties, as well as the lncRNAs derived from these exosomes, have emerged as one of the innovative tools in wound healing. This review article aims to narrate the cellular and molecular roles of exosome-derived lncRNAs from stem cells in enhancing wound healing with a focus on mesenchymal stem cells.
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Affiliation(s)
- Ali Morabbi
- Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, 47416-95447, Iran
| | - Mohammad Karimian
- Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, 47416-95447, Iran.
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Hashemi SS, Sanati P, Rafati A. The inducing effect of epidermal growth factor on acellular dermal matrix in a rat model of skin regeneration. J Wound Care 2025; 34:137-145. [PMID: 39928476 DOI: 10.12968/jowc.2021.0286] [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: 02/12/2025]
Abstract
OBJECTIVE Tissue engineering, a novel approach in dermatology, has resulted in the development of scaffolds as skin substitutes that have accelerated wound healing. The aim of the present study was to synthesise acellular dermal matrix (ADM) as a dermal alternative and assess the effect of human epidermal growth factor (EGF) on the proliferation and migration of seeded fibroblast cells. METHOD ADM from fresh, full-thickness human skin was developed and characterised. Next, foreskin fibroblast cells were isolated, cultured and characterised. The fibroblast cells were sown into the ADM in two groups: one with EGF and one without EGF. We assessed the adhesion and proliferation of the cells on the scaffold by scanning electron microscopy, and thiazolyl blue tetrazolium bromide and 4',6-diamidino-2-phenylindole staining. For the animal study, 30 rats were divided into two equal groups at random (ADM, ADM+EGF). Wound healing was assessed macroscopically, histologically and by real-time polymerase chain reaction for Bax and Bcl-2 gene expression. RESULTS The ADM characterisation results showed that the scaffold was dense and integral with good stretching. The morphology and phenotype of the isolated fibroblast cells confirmed their identity. The fibroblast cells cultured on the ADM showed proliferation, which improved with the addition of EGF. In the animal model, EGF addition caused significantly (p<0.05) improved wound healing compared with isolated ADM; it also resulted in increased Bcl-2 and reduced Bax expressions. CONCLUSION A combination of ADM, fibroblast cells and EGFs could serve as skin substitutes and represent a novel therapeutic methodology for treating burns and hard-to-heal wounds.
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Affiliation(s)
- Seyedeh-Sara Hashemi
- Burn and Wound Healing Research Center and Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Fars, Iran
| | - Parisa Sanati
- Burn and Wound Healing Research Center and Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Fars, Iran
- Iran National Elite Foundation, Tehran, Iran
| | - AliReza Rafati
- Division of Pharmacology and Pharmaceutical Chemistry, Sarvestan Branch, Islamic Azad University, Sarvestan, Iran
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Ran F, Mu K, Zhou L, Peng L, Liu G, Liu Y, Pang Y, Feng G, Guo C, Wang T, Luo Q. Plant-Derived B-CGT Hydrogel Accelerates Diabetic Wound Healing Through Multitarget Modulation of Inflammation, Angiogenesis, and Tissue Remodeling. Gels 2025; 11:104. [PMID: 39996646 PMCID: PMC11854240 DOI: 10.3390/gels11020104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 01/12/2025] [Accepted: 01/27/2025] [Indexed: 02/26/2025] Open
Abstract
Diabetic wound healing presents significant challenges due to impaired angiogenesis, chronic inflammation, and cellular dysfunction. Building on previous research, this study further explores the potential of a plant-derived glucosyloxybenzyl 2-isobutylmalates (B-CGT) hydrogel in promoting diabetic wound healing. Network pharmacology and molecular docking analyses suggest that B-CGT may regulate key mechanisms, such as apoptosis, inflammation, and matrix remodeling, through core targets including SIRT1, CASP8, and MMP8. In vivo studies further demonstrated that B-CGT hydrogel significantly accelerated wound closure in diabetic mice, enhanced angiogenesis, promoted collagen deposition, and achieved immune balance by modulating macrophage polarization, thereby shifting the inflammatory environment toward a repair state. Moreover, B-CGT hydrogel significantly improved the wound microenvironment by upregulating VEGF expression and exerting antioxidant effects. By combining theoretical predictions with experimental validation, this study elucidates the multi-target synergistic regulatory mechanisms of B-CGT hydrogel. These findings provide new research directions for addressing immune imbalance and angiogenesis defects in diabetic wound healing and lay a scientific foundation for the optimization and application of chronic wound treatment strategies.
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Affiliation(s)
| | | | | | | | - Gang Liu
- College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; (F.R.); (K.M.); (Y.P.)
| | - Yuchen Liu
- College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; (F.R.); (K.M.); (Y.P.)
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