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Cai D, Liu T, Weng W, Zhu X. Research Progress on Extracellular Matrix-Based Composite Materials in Antibacterial Field. Biomater Res 2025; 29:0128. [PMID: 39822928 PMCID: PMC11735711 DOI: 10.34133/bmr.0128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 11/07/2024] [Accepted: 12/14/2024] [Indexed: 01/19/2025] Open
Abstract
Due to their exceptional cell compatibility, biodegradability, and capacity to trigger tissue regeneration, extracellular matrix (ECM) materials have drawn considerable attention in tissue healing and regenerative medicine. Interestingly, these materials undergo continuous degradation and release antimicrobial peptides (AMPs) while simultaneously promoting tissue regeneration, thereby exerting a potent antibacterial effect. On this basis, a variety of basic properties of ECM materials, such as porous adsorption, hydrophilic adsorption, group crosslinking, and electrostatic crosslinking, can be used to facilitate the integration of ECM materials and antibacterial agents through physical and chemical approaches in order to enhance the antibacterial efficacy. This article reviews the recent advancements in the study of ECM antibacterial materials, including the antibacterial function and antibacterial mechanism of free-standing ECM materials and ECM-based composite materials. In addition, the urgent challenges and future research prospects of ECM materials in the anti-infection industry are discussed.
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Affiliation(s)
- Dan Cai
- Department of Orthopedics, The First People’s Hospital of Huzhou,
First Affiliated Hospital of Huzhou University, Zhejiang 313000, China
| | - Tuoqin Liu
- Intensive Care Unit, People’s Hospital of Wuxing District, Wuxing District Maternal and Child Health Hospital, Huzhou, Zhejiang 313000, China
| | - Wei Weng
- Department of Orthopedics, The First People’s Hospital of Huzhou,
First Affiliated Hospital of Huzhou University, Zhejiang 313000, China
| | - Xinhong Zhu
- Department of Orthopedics, The First People’s Hospital of Huzhou,
First Affiliated Hospital of Huzhou University, Zhejiang 313000, China
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Chi Y, Song C, Jia Q, Zhang R, Sun F, Li Z, Jia Y, An X, Wang Z, Li J. A metal coordination polymer nanoparticle synergistically re-establishes acidosis and enhances chemodynamic therapy for Glioblastoma. Acta Biomater 2025; 192:290-301. [PMID: 39608659 DOI: 10.1016/j.actbio.2024.11.042] [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: 08/17/2024] [Revised: 11/12/2024] [Accepted: 11/25/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND Chemodynamic therapy (CDT) has become increasingly important as a tumor treatment strategy, which relies on intracellular acid and hydrogen peroxide to kill tumor cells by generating hydroxyl radicals (·OH) through Fenton/Fenton-like reactions. However, the weakly alkaline intracellular environment considerably caused by the efflux of lactate and H+ from glioblastoma cells is not conducive to CDT performance. Intracellular acidification induced by inhibiting the transmembrane monocarboxylate transporter 4 (MCT4) can enhance the therapeutic efficacy of CDT. Existing approaches suffer from insufficient MCT4 inhibition, involve complex drug synthesis, and have many unsatisfactory side effects. METHODS In this study, we constructed an anti-tumor nanoparticle formed by self-assembly driven by the coordination interaction of Fe3+ and α-cyano-4-hydroxycinnamate (CHC) to avoid safety issues posed by excessive modification. Fe-CHC nanoparticles were designed to decrease intracellular pH through inhibition of MCT4, which transports lactate/H+ to the extracellular space. The resulting intracellular accumulation of lactate and H+ led to fatal acidosis and promoted ·OH generated by Fenton/Fenton-like reactions with the presence of the Fe3+, thus enhancing CDT-induced tumor cell death. RESULTS In vitro and in vivo results revealed that Fe-CHC exerted a significant synergistic anti-tumor effect by re-establishing acidosis and enhancing CDT in glioblastoma. Furthermore, the decreased H+outside the cells caused by the inhibition of lactate/H+ efflux hindered extracellular matrix degradation, thereby inhibiting tumor metastasis. CONCLUSION Fe-CHC is an effective anti-cancer agent against glioblastoma. This study provides valuable insights for developing acid-modulating anti-tumor nanoparticles, as well as enriching and optimizing the application of CDT in tumor therapy. STATEMENT OF SIGNIFICANCE Our study pioneers the Fe-CHC nanoparticle, a metal-coordination polymer that targets MCT4 in glioblastoma cells to restore intracellular acidity and synergize with Fe3+ to boost chemodynamic therapy (CDT). Unlike other studies, Fe3+ and CHC work together to maximize the therapeutic potential and safety of Fe-CHC with minimal complexity. This innovative approach not only increased the production of reactive oxygen species within tumor cells, but also hindered tumor metastasis. Our work has important scientific implications for tumor microenvironment regulation and the application of CDT, and will provide a promising pathway for the treatment of aggressive cancers and attract a wide audience through its scientific implications.
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Affiliation(s)
- Yajing Chi
- School of Medicine, Nankai University, Tianjin, 300071, China; Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi, 710126, China
| | - Chaoqi Song
- Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi, 710126, China
| | - Qian Jia
- Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi, 710126, China; Guangzhou Institute of Technology, Xidian University, Guangzhou, GuangDong, 510000, China.
| | - Ruili Zhang
- Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi, 710126, China
| | - Fang Sun
- Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi, 710126, China
| | - Zheng Li
- Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi, 710126, China
| | - Yuanyuan Jia
- Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi, 710126, China
| | - Xian An
- Department of Radiotherapy, Chinese PLA General Hospital, Beijing, 100071, China
| | - Zhongliang Wang
- Lab of Molecular Imaging and Translational Medicine (MITM), Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment, Xi'an, Shaanxi, 710126, China.
| | - Jianxiong Li
- School of Medicine, Nankai University, Tianjin, 300071, China; Department of Radiotherapy, Chinese PLA General Hospital, Beijing, 100071, China.
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Di Nubila A, Doulgkeroglou MN, Gurdal M, Korntner SH, Zeugolis DI. In vitro and in vivo assessment of a non-animal sourced chitosan scaffold loaded with xeno-free umbilical cord mesenchymal stromal cells cultured under macromolecular crowding conditions. BIOMATERIALS AND BIOSYSTEMS 2024; 16:100102. [PMID: 40225717 PMCID: PMC11993840 DOI: 10.1016/j.bbiosy.2024.100102] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 06/06/2024] [Accepted: 10/08/2024] [Indexed: 04/15/2025] Open
Abstract
There is an increasing demand to not only accelerate the development of advanced therapy tissue engineered medicines, but to also eliminate xenogeneic materials from their development cycle. With these in mind, herein we first assessed the influence of carrageenan as macromolecular crowding agent to enhance and accelerate extracellular matrix deposition in xeno-free human umbilical cord mesenchymal stromal cell cultures and we developed and characterised a non-animal sourced chitosan scaffold. Following appropriate in vitro experimentation, a splinted nude mouse wound healing model was used to assess wound closure and scar size of non-treated control, non-animal sourced chitosan scaffold, non-animal sourced chitosan scaffold loaded with xeno-free human umbilical cord mesenchymal stromal cells and non-animal sourced chitosan scaffold loaded with xeno-free human umbilical cord mesenchymal stromal cells cultured under macromolecular crowding conditions groups. Across all three donors, carrageenan supplementation significantly increased collagen deposition at day 5, day 8 and day 11 without affecting cell morphology, viability, DNA concentration and metabolic activity. Through freeze drying, a non-animal sourced chitosan sponge was developed with appropriate structural and mechanical properties for wound healing applications. In vitro biological analysis made apparent that neither the scaffold nor macromolecular crowding negatively impacted xeno-free human umbilical cord mesenchymal stromal cell metabolic activity and proliferation. In vivo biological analysis revealed no significant differences between the groups in wound closure and scar size, raising question about the suitability of the model. In any case, this work sets the foundations for the development of completely xeno-free tissue engineered medicines.
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Affiliation(s)
- Alessia Di Nubila
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL) and Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, University of Galway, Galway, Ireland
| | - Meletios-Nikolaos Doulgkeroglou
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL) and Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, University of Galway, Galway, Ireland
| | - Mehmet Gurdal
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Charles Institute of Dermatology, Conway Institute of Biomolecular & Biomedical Research and School of Mechanical & Materials Engineering, University College Dublin (UCD), Dublin, Ireland
| | - Stefanie H. Korntner
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL) and Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, University of Galway, Galway, Ireland
| | - Dimitrios I. Zeugolis
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL) and Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, University of Galway, Galway, Ireland
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Charles Institute of Dermatology, Conway Institute of Biomolecular & Biomedical Research and School of Mechanical & Materials Engineering, University College Dublin (UCD), Dublin, Ireland
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Vanti G, Poondla N, Manogaran P, Teradal N, S V, Kaulgud R, Kurjogi M. Synthesis and Characterization of Multifunctional Chitosan-Silver Nanoparticles: An In-Vitro Approach for Biomedical Applications. Pharmaceuticals (Basel) 2024; 17:1229. [PMID: 39338391 PMCID: PMC11434662 DOI: 10.3390/ph17091229] [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: 07/04/2024] [Revised: 09/10/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Antibiotics are successful in promoting health quality by preventing various infectious diseases and minimizing mortality and morbidity all over the world. However, the indiscriminate use of antibiotics has led to the emergence of multi-drug-resistant bacteria, which pose a serious threat to health care sector. Therefore, it is necessary to develop novel antimicrobial agents with versatile characteristics, such as antibacterial activity, low toxicity, wound healing potency, and antioxidant property. In this context, silver chitosan nanoparticles were synthesized in the present study, and their physical characterization revealed that the size of synthesized chitosan-silver nanoparticles was 14-25 nm, with positive surface charge. The functional groups and crystalline nature of the nanoparticles were confirmed by FT-IR and XRD analysis. Further, the silver chitosan nanoparticles showed antibacterial activity against two important clinical pathogens, S. aureus and E. coli. The MTT assay carried out in the present study showed that the synthesized nanoparticles are non-toxic to host cells. A scratch assay on fibroblast cells (L292) demonstrated that the silver chitosan nanoparticles showed promising wound healing activity. A fluorescent DCFH-DA staining assay revealed anantioxidant property of the synthesized nanoparticles. Overall, the study emphasizes the versatile nature of synthesized chitosan-silver nanoparticles, suggesting their great compatibility for biomedical applications.
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Affiliation(s)
- Gulamnabi Vanti
- Multidisciplinary Research Unit, Karnataka Medical College and Research Institute, Hubli 580021, India
| | - Naresh Poondla
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Center for Global Health Research, Saveetha Medical College& Hospital, Chennai 602105, India
- Department of Applied Chemistry, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Science (SIMATS), Chennai 602105, India
| | - Prasath Manogaran
- Department of Clinical and Translational Sciences, Marshall University, Huntington, WV 25755, USA
| | - Nagappa Teradal
- Department of Chemistry, J. S. S. Arts, Science and Commerce College, Gokak 591307, India
| | - Veeresh S
- Multidisciplinary Research Unit, Karnataka Medical College and Research Institute, Hubli 580021, India
| | - Ram Kaulgud
- Multidisciplinary Research Unit, Karnataka Medical College and Research Institute, Hubli 580021, India
| | - Mahantesh Kurjogi
- Multidisciplinary Research Unit, Karnataka Medical College and Research Institute, Hubli 580021, India
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Hajihosseintehrani M, Amini A, Heidari M, Gholipourmalekabadi M, Fadaei Fathabady F, Mostafavinia A, Ahmadi H, Khodadadi M, Naser R, Zare F, Alizadeh S, Moeinian N, Chien S, Bayat M. The Application of Photobiomodulation and Stem Cells Seeded on the Scaffold Accelerates the Wound Healing Process in Mice. J Lasers Med Sci 2024; 15:e40. [PMID: 39381785 PMCID: PMC11459249 DOI: 10.34172/jlms.2024.40] [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: 03/03/2024] [Accepted: 05/08/2024] [Indexed: 10/10/2024]
Abstract
Introduction: The purpose of this research was to test the impact of seeding a hydrogel chitosan scaffold (HCS) with human adipose-derived stem cells (hADSCs) under the influence of photobiomodulation (PBM) on the remodeling step on the wound repairing process in mice. Methods: Thirty mice were randomly assigned to five groups (n=6 per group ): The control group (group 1) consisted of mice without any intervention. In group 2, an HCS was implanted into the wound. In group 3, a combination of HCS+hADSC was inserted into the wound. In group 4, an HCS was inserted into the wound and PBM was applied. In group 5, a combination of HCS+hADSCs was inserted into the wound, followed by PBM treatment. Results: Improvements in the injury closing rate (WCR) and microbial flora were observed in all groups. However, the highest WCRs were observed in group s 5, 4, 3, and 2 (all P values were 0.000). Groups 3-5 showed increased wound strength compared to group s 1 and 2, with group 2 demonstrating better results than group 1 (P values ranged from 0.000 to 0.013). Although group s 3-5 showed increases in certain stereological elements compared to group s 1 and 2, group 2 exhibited superior results in comparison with group 1 (P values ranged from 0.000 to 0.049). Conclusion: The joined use of HCS+hADSCs+PBM significantly accelerated the wound healing process during the maturation phase in healthy mice. This approach demonstrated superior wound healing compared to the use of HCS alone, hADSCs+HCS, or PBM+HCS. The findings suggest an additive effect when HCS+hADSCs+PBM are combined.
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Affiliation(s)
- Masoumeh Hajihosseintehrani
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Abdollah Amini
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Mohammadhossein Heidari
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Mazaher Gholipourmalekabadi
- Department of Tissue Engineering & Regenerative Medicine, Iran University of Medical Sciences, Hemmat Highway, Tehran, Iran
| | - Fatemeh Fadaei Fathabady
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Atarodalsadat Mostafavinia
- Department of Anatomical Sciences and Cognitive Neuroscience at the Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Houssein Ahmadi
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Maryam Khodadadi
- Xi’an jiaotong University School of Stomatology, Xi’an, Shaanxi Province, China
| | - Reza Naser
- Tissue Engineering Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fateme Zare
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Sanaz Alizadeh
- Department of Anatomical Sciences and Cognitive Neuroscience at the Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Nafiseh Moeinian
- Department of Biology and Anatomical Sciences at Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
| | - Sufan Chien
- Price Institute of Surgical Research at the University of Louisville and Noveratech LLC of Louisville in Louisville, KY, USA
| | - Mohammad Bayat
- Department of Tissue Engineering & Regenerative Medicine, Iran University of Medical Sciences, Hemmat Highway, Tehran, Iran
- Price Institute of Surgical Research at the University of Louisville and Noveratech LLC of Louisville in Louisville, KY, USA
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Shi S, Lu W, Gu X, Lin Q. Efficacy of Gentamicin-Loaded Chitosan Nanoparticles Against Staphylococcus aureus Internalized in Osteoblasts. Microb Drug Resist 2024; 30:196-202. [PMID: 38579161 DOI: 10.1089/mdr.2023.0066] [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: 04/07/2024] Open
Abstract
Staphylococcus aureus, the principal causative agent of osteomyelitis, can be internalized by osteoblasts and thereby escape from immune phagocytes and many kinds of antibiotics. To deliver antibiotics into osteoblasts to kill S. aureus in the intracellular environment, we developed gentamicin-loaded chitosan nanoparticles and evaluated their intracellular bactericidal effect. We found decreased numbers of S. aureus cells in infected osteoblasts treated with gentamicin-loaded chitosan nanoparticles. The cytotoxicity of the nanoparticles was evaluated by CCK-8 assay. There was no significant viability decrease at all tested concentrations. In conclusion, our results provide evidence for the potential use of gentamicin-loaded chitosan nanoparticles to enhance the delivery of gentamicin into cells and for their antibacterial effect against internalized S. aureus in the intracellular environment of osteoblasts.
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Affiliation(s)
- Sifeng Shi
- Department of Orthopedic Surgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Wei Lu
- Department of Orthopedic Surgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Xu Gu
- Department of Orthopedic Surgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Qiang Lin
- Department of Orthopedic Surgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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Wu S, Sun S, Fu W, Yang Z, Yao H, Zhang Z. The Role and Prospects of Mesenchymal Stem Cells in Skin Repair and Regeneration. Biomedicines 2024; 12:743. [PMID: 38672102 PMCID: PMC11048165 DOI: 10.3390/biomedicines12040743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 03/01/2024] [Accepted: 03/11/2024] [Indexed: 04/28/2024] Open
Abstract
Mesenchymal stem cells (MSCs) have been recognized as a cell therapy with the potential to promote skin healing. MSCs, with their multipotent differentiation ability, can generate various cells related to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. In addition, MSCs promote neovascularization, cellular regeneration, and tissue healing through mechanisms including paracrine and autocrine signaling. Due to these characteristics, MSCs have been extensively studied in the context of burn healing and chronic wound repair. Furthermore, during the investigation of MSCs, their unique roles in skin aging and scarless healing have also been discovered. In this review, we summarize the mechanisms by which MSCs promote wound healing and discuss the recent findings from preclinical and clinical studies. We also explore strategies to enhance the therapeutic effects of MSCs. Moreover, we discuss the emerging trend of combining MSCs with tissue engineering techniques, leveraging the advantages of MSCs and tissue engineering materials, such as biodegradable scaffolds and hydrogels, to enhance the skin repair capacity of MSCs. Additionally, we highlight the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies as a future direction in stem cell-based treatments, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.
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Affiliation(s)
- Si Wu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Shengbo Sun
- School of Basic Medical Sciences, Capital Medical University, Beijing 100050, China
| | - Wentao Fu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Zhengyang Yang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Hongwei Yao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- National Clinical Research Center for Digestive Diseases, Beijing 100050, China
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Ismail EA, Omolo CA, Gafar MA, Khan R, Nyandoro VO, Salifu EY, Govender T. Multi-functional pH-responsive and biomimetic chitosan-based nanoplexes for targeted delivery of ciprofloxacin against bacterial sepsis. Int J Biol Macromol 2024; 262:130046. [PMID: 38336334 DOI: 10.1016/j.ijbiomac.2024.130046] [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: 12/07/2023] [Revised: 01/31/2024] [Accepted: 02/06/2024] [Indexed: 02/12/2024]
Abstract
Bacterial sepsis is a mortal syndromic disease characterized by a complex pathophysiology that hinders effective targeted therapy. This study aimed to develop multifunctional, biomimetic and pH-responsive ciprofloxacin-loaded chitosan (CS)/sodium deoxycholic acid (SDC) nanoplexes (CS/SDC) nanoplexes with the ability to target and modulate the TLR4 pathway, activated during sepsis. The formulated nanoplexes were characterized in terms of physicochemical properties, in silico and in vitro potential biological activities. The optimal formulation showed good biocompatibility and stability with appropriate physicochemical parameters. The surface charge changed from negative at pH 7.4 to positive at pH 6.0 accompanied with a significantly faster release of CIP at pH 6.0 compared to 7.4. The biomimicry was elucidated by in silico tools and MST and results confirmed strong binding between the system and TLR4. Furthermore, the system revealed 4- and 2-fold antibacterial enhancement at acidic pH, and 3- and 4-fold better antibiofilm efficacy against Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) respectively, compared to bare CIP. In addition, enhanced bacterial efflux pump inhibition was demonstrated by CS/SDC nanoplexes. Finally, the developed nanosystem showed excellent antioxidant activity against DPPH radicals. Taken together, the study confirmed the multi-functionalities of CS/SDC nanoplexes and their potential benefits in improving bacterial sepsis therapy.
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Affiliation(s)
- Eman A Ismail
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa; Department of Pharmaceutics, Faculty of Pharmacy, University of Gezira, Wad Medani, Sudan
| | - Calvin A Omolo
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa; United States International University-Africa, School of Pharmacy and Health Sciences, Department of Pharmaceutics, P. O. Box 14634-00800, Nairobi, Kenya.
| | - Mohammed A Gafar
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa
| | - Rene Khan
- Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Vincent O Nyandoro
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa
| | - Elliasu Y Salifu
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Cape Town 7505, South Africa
| | - Thirumala Govender
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa.
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Fu XY, Jiang ZY, Zhang CY, Shen LY, Yan XD, Li XK, Lin JY, Wang Y, Mao XL, Li SW. New hope for esophageal stricture prevention: A prospective single-center trial on acellular dermal matrix. World J Gastrointest Endosc 2023; 15:725-734. [PMID: 38187918 PMCID: PMC10768038 DOI: 10.4253/wjge.v15.i12.725] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 10/22/2023] [Accepted: 11/03/2023] [Indexed: 12/15/2023] Open
Abstract
BACKGROUND Given the high incidence of esophageal cancer in China, an increasing number of patients there are undergoing endoscopic mucosal dissection (ESD). Although the 5-year survival rate after ESD can exceed 95%, esophageal stricture, the most common and serious postoperative complication, affects the long-term prognosis of patients and the quality of life. Autologous mucosal grafts have proven to be successful in preventing stricture after ESD for early esophageal cancer.
AIM To examine the viability of acellular dermal matrix (ADM) as an alternative to autologous mucosa for the prevention of stricture after ESD.
METHODS This is a prospective, single-center, controlled study. Consecutive patients who underwent ESD surgery and were willing to undergo autologous mucosal transplantation were recruited between January 1 and December 31, 2017. Consecutive patients who underwent ESD surgery and were willing to undergo ADM transplantation were recruited between January 1 to December 31, 2019. A final three-year follow-up of patients who received transplants was conducted.
RESULTS Based on the current incidence of esophageal stricture, the sample size required for both the autologous mucosal graft group and the ADM group was calculated to be 160 cases. Due to various factors, a total of 20 patients with autologous mucosal grafts and 25 with ADM grafts were recruited. Based on the inclusion exclusion and withdrawal criteria, 9 patients ultimately received autologous mucosal grafts and completed the follow-up, while 11 patients received ADM grafts and completed the follow-up. Finally, there were 2 cases of stenosis in the autologous mucosal transplantation group with a stenosis rate of 22.22% and 2 cases of stenosis in the ADM transplantation group with a stenosis rate of 18.18%, with no significant difference noted between the groups (P = 0.94).
CONCLUSION In this prospective, single-center, controlled trial, we compared the effectiveness of autologous mucosa transplantation and ADM for the prevention of esophageal stricture. Due to certain condition limitations, we were unable to recruit sufficient subjects meeting our target requirements. However, we implemented strict inclusion, exclusion, and withdrawal criteria and successfully completed three years of follow-up, resulting in valuable clinical insights. Based on our findings, we hypothesize that ADM may be similarly effective to autologous mucosal transplantation in the prevention of esophageal stricture, offering a comparable and alternative approach. This study provides a new therapeutic idea and direction for the prevention of esophageal stricture.
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Affiliation(s)
- Xin-Yu Fu
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
| | - Zhen-Yu Jiang
- Department of Gastroenterology, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, Inner Mongolia Autonomous Region, China
| | - Chen-Yang Zhang
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
| | - Ling-Yan Shen
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
| | - Xiao-Dan Yan
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
| | - Xiao-Kang Li
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
- Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo 1540001, Japan
| | - Jia-Ying Lin
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
| | - Yi Wang
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
| | - Xin-Li Mao
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
| | - Shao-Wei Li
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
- Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
- Institute of Digestive Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
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10
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Ning X, Liu N, Sun T, You Y, Luo Y, Kang E, Chen Z, Wang Y, Ren J. Promotion of adipose stem cell transplantation using GelMA hydrogel reinforced by PLCL/ADM short nanofibers. Biomed Mater 2023; 18:065003. [PMID: 37647920 DOI: 10.1088/1748-605x/acf551] [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: 02/16/2023] [Accepted: 08/30/2023] [Indexed: 09/01/2023]
Abstract
Adipose-derived mesenchymal stem cells (ADSCs) show poor survival after transplantation, limiting their clinical application. In this study, a series of poly(l-lactide-co-ϵ-caprolactone) (PLCL)/acellular dermal matrix (ADM) nanofiber scaffolds with different proportions were prepared by electrospinning. By studying their morphology, hydrophilicity, tensile mechanics, and biocompatibility, PLCL/ADM nanofiber scaffolds with the best composition ratio (PLCL:ADM = 7:3) were selected to prepare short nanofibers. And based on this, injectable gelatin methacryloyl (GelMA) hydrogel loaded with PLCL/ADM short nanofibers (GelMA-Fibers) was constructed as a transplantation vector of ADSCs. ADSCs and GelMA-Fibers were co-cultured, and the optimal loading concentration of PLCL/ADM nanofibers was investigated by cell proliferation assay, live/dead cell staining, and cytoskeleton stainingin vitro. In vivoinvestigations were also performed by H&E staining, Oil red O staining, and TUNEL staining, and the survival and apoptosis rates of ADSCs transplantedin vivowere analyzed. It was demonstrated that GelMA-Fibers could effectively promote the proliferation of ADSCsin vitro. Most importantly, GelMA-Fibers increased the survival rate of ADSCs transplantation and decreased their apoptosis rate within 14 d. In conclusion, the constructed GelMA-Fibers would provide new ideas and options for stem cell tissue engineering and stem cell-based clinical therapies.
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Affiliation(s)
- Xuchao Ning
- Department of Cosmetic and Plastic Surgery, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China
- Department of Plastic Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, People's Republic of China
| | - Na Liu
- Institute of Neuroregeneration and Neurorehabilitation, Qingdao Medical College, Qingdao University, Qingdao, People's Republic of China
| | - Tiancai Sun
- Collaborative Innovation Center for Nanomaterials & Devices, College of Physics, Qingdao University, Qingdao, People's Republic of China
| | - Yong You
- Department of Cosmetic and Plastic Surgery, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China
| | - Yanan Luo
- Department of Cosmetic and Plastic Surgery, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China
| | - Enhao Kang
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China
| | - Zhenyu Chen
- Department of Cosmetic and Plastic Surgery, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China
| | - Yuanfei Wang
- Central Laboratory, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, People's Republic of China
| | - Jizhen Ren
- Department of Cosmetic and Plastic Surgery, Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China
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11
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Mensah RA, Trotta F, Briggs E, Sharifulden NS, Silva LVB, Keskin-Erdogan Z, Diop S, Kureshi AK, Chau DYS. A Sustainable, Green-Processed, Ag-Nanoparticle-Incorporated Eggshell-Derived Biomaterial for Wound-Healing Applications. J Funct Biomater 2023; 14:450. [PMID: 37754864 PMCID: PMC10531947 DOI: 10.3390/jfb14090450] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/18/2023] [Accepted: 08/28/2023] [Indexed: 09/28/2023] Open
Abstract
The eggshell membrane (ESM) is a natural biomaterial with unique physical and mechanical properties that make it a promising candidate for wound-healing applications. However, the ESM's inherent properties can be enhanced through incorporation of silver nanoparticles (AgNPs), which have been shown to have antimicrobial properties. In this study, commercially produced AgNPs and green-processed AgNPs were incorporated into ESM and evaluated for their physical, biological, and antimicrobial properties for potential dermal application. The ESM was extracted using various techniques, and then treated with either commercially produced AgNPs (Sigma-Aldrich, Poole, UK) or green-synthesized AgNPs (Metalchemy, London, UK) to produce AgNPs-ESM samples. The physical characteristics of the samples were evaluated using scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy, and the biological properties were assessed through in vitro studies using human dermal fibroblasts (HDFs) and BJ cells. The SEM analysis of the AgNPs-ESM samples showed localization of AgNPs on the ESM surface, and that the ESM maintained its structural integrity following AgNP incorporation. The FTIR confirmed loading of AgNPs to ESM samples. The biological studies showed that the 5 μg/mL AgNPs-ESM samples were highly biocompatible with both HDFs and BJ cells, and had good viability and proliferation rates. Additionally, the AgNPs-ESM samples demonstrated pro-angiogenic properties in the CAM assay, indicating their potential for promoting new blood vessel growth. Assessment of the antimicrobial activity of the enhanced AgNPs/ESMs was validated using the International Standard ISO 16869:2008 methodology and exploited Cladosporium, which is one of the most commonly identified fungi in wounds, as the test microorganism (≥5 × 106 cells/mL). The AgNPs-ESM samples displayed promising antimicrobial efficacy as evidenced by the measured zone of inhibition. Notably, the green-synthesized AgNPs demonstrated greater zones of inhibition (~17 times larger) compared to commercially available AgNPs (Sigma-Aldrich). Although both types of AgNP exhibited long-term stability, the Metalchemy-modified samples demonstrated a slightly stronger inhibitory effect. Overall, the AgNPs-ESM samples developed in this study exhibited desirable physical, biological, and antimicrobial properties for potential dermal wound-dressing applications. The use of green-processed AgNPs in the fabrication of the AgNPs-ESM samples highlights the potential for sustainable and environmentally friendly wound-healing therapies. Further research is required to assess the long-term biocompatibility and effectiveness of these biomaterials in vivo.
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Affiliation(s)
- Rosemond A. Mensah
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
| | - Federico Trotta
- Metalchemy Limited, 71-75 Shelton Street, London WC2H 9JQ, UK
| | - Emily Briggs
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
- Department of Materials, Henry Royce Institute, The University of Manchester, Rumford Street, Manchester M13 9PL, UK
| | - Nik San Sharifulden
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
| | - Lady V. Barrios Silva
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
| | - Zalike Keskin-Erdogan
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
- Chemical Engineering Department, Imperial College London, Exhibition Rd, South Kensington, London SW7 2BX, UK
| | - Seyta Diop
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
| | - Alvena K. Kureshi
- Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, Charles Bell House, Foley Street, London W1W 7TY, UK
| | - David Y. S. Chau
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
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12
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Vishnu J, Kesavan P, Shankar B, Dembińska K, Swiontek Brzezinska M, Kaczmarek-Szczepańska B. Engineering Antioxidant Surfaces for Titanium-Based Metallic Biomaterials. J Funct Biomater 2023; 14:344. [PMID: 37504839 PMCID: PMC10381466 DOI: 10.3390/jfb14070344] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/21/2023] [Accepted: 06/27/2023] [Indexed: 07/29/2023] Open
Abstract
Prolonged inflammation induced by orthopedic metallic implants can critically affect the success rates, which can even lead to aseptic loosening and consequent implant failure. In the case of adverse clinical conditions involving osteoporosis, orthopedic trauma and implant corrosion-wear in peri-implant region, the reactive oxygen species (ROS) activity is enhanced which leads to increased oxidative stress. Metallic implant materials (such as titanium and its alloys) can induce increased amount of ROS, thereby critically influencing the healing process. This will consequently affect the bone remodeling process and increase healing time. The current review explores the ROS generation aspects associated with Ti-based metallic biomaterials and the various surface modification strategies developed specifically to improve antioxidant aspects of Ti surfaces. The initial part of this review explores the ROS generation associated with Ti implant materials and the associated ROS metabolism resulting in the formation of superoxide anion, hydroxyl radical and hydrogen peroxide radicals. This is followed by a comprehensive overview of various organic and inorganic coatings/materials for effective antioxidant surfaces and outlook in this research direction. Overall, this review highlights the critical need to consider the aspects of ROS generation as well as oxidative stress while designing an implant material and its effective surface engineering.
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Affiliation(s)
- Jithin Vishnu
- Department of Mechanical Engineering, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana 690525, India
| | - Praveenkumar Kesavan
- Department of Materials Engineering, Indian Institute of Science, Bangalore 560012, India
| | - Balakrishnan Shankar
- Department of Mechanical Engineering, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana 690525, India
| | - Katarzyna Dembińska
- Department of Environmental Microbiology and Biotechnology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
| | - Maria Swiontek Brzezinska
- Department of Environmental Microbiology and Biotechnology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
| | - Beata Kaczmarek-Szczepańska
- Department of Biomaterials and Cosmetic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
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13
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Mohammadyari F, Parvin S, Khorvash M, Amini A, Behzadi A, HajEbrahimi R, Kasaei F, Olangian-Tehrani S. Acellular dermal matrix in reconstructive surgery: Applications, benefits, and cost. FRONTIERS IN TRANSPLANTATION 2023; 2:1133806. [PMID: 38993878 PMCID: PMC11235262 DOI: 10.3389/frtra.2023.1133806] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 02/13/2023] [Indexed: 07/13/2024]
Abstract
Modern tissue engineering has made substantial advancements that have revolutionized plastic surgery. Acellular dermal matrix (ADM) is an example that has gained considerable attention recently. ADM can be made from humans, bovines, or porcine tissues. ADM acts as a scaffold that incorporates into the recipient tissue. It is gradually infiltrated by fibroblasts and vascularized. Fortunately, many techniques have been used to remove cellular and antigenic components from ADM to minimize immune system rejection. ADM is made of collagen, fibronectin, elastin, laminin, glycosaminoglycans, and hyaluronic acid. It is used in critical wounds (e.g., diabetic wounds) to protect soft tissue and accelerate wound healing. It is also used in implant-based breast reconstruction surgery to improve aesthetic outcomes and reduce capsule contracture risk. ADM has also gained attention in abdominal and chest wall defects. Some studies have shown that ADM is associated with less erosion and infection in abdominal hernias than synthetic meshes. However, its higher cost prevents it from being commonly used in hernia repair. Also, using ADM in tendon repair (e.g., Achilles tendon) has been associated with increased stability and reduced rejection rate. Despite its advantages, ADM might result in complications such as hematoma, seroma, necrosis, and infection. Moreover, ADM is expensive, making it an unsuitable option for many patients. Finally, the literature on ADM is insufficient, and more research on the results of ADM usage in surgeries is needed. This article aims to review the literature regarding the application, Benefits, and costs of ADM in reconstructive surgery.
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Affiliation(s)
| | - Sadaf Parvin
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Khorvash
- School of Medicine, Islamic Azad University of Medical Sciences, Tehran, Iran
| | - Amirhasan Amini
- School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | | | | | - Fatemeh Kasaei
- School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Sepehr Olangian-Tehrani
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Avicennet, Tehran, Iran
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Daniele E, Bosio L, Hussain NA, Ferrari B, Ferrari S, Barbaro V, McArdle B, Rassu N, Mura M, Parmeggiani F, Ponzin D. Denuded Descemet's membrane supports human embryonic stem cell-derived retinal pigment epithelial cell culture. PLoS One 2023; 18:e0281404. [PMID: 36745611 PMCID: PMC9901769 DOI: 10.1371/journal.pone.0281404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 01/22/2023] [Indexed: 02/07/2023] Open
Abstract
Recent clinical studies suggest that retinal pigment epithelial (RPE) cell replacement therapy may preserve vision in retinal degenerative diseases. Scaffold-based methods are being tested in ongoing clinical trials for delivering pluripotent-derived RPE cells to the back of the eye. The aim of this study was to investigate human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells survival and behaviour on a decellularized Descemet's Membrane (DM), which may be of clinical relevance in retinal transplantation. DMs were isolated from human donor corneas and treated with thermolysin. The DM surface topology and the efficiency of the denudation method were evaluated by atomic force microscope, scanning electron microscopy and histology. hESC-RPE cells were seeded onto the endothelial-side surface of decellularized DM in order to determine the potential of the membrane to support hESC-RPE cell culture, alongside maintaining their viability. Integrity of the hESC-RPE monolayer was assessed by measuring transepithelial resistance. RPE-specific gene expression and growth factors secretion were assessed to confirm maturation and functionality of the cells over the new substrate. Thermolysin treatment did not affect the integrity of the tissue, thus ensuring a reliable method to standardize the preparation of decellularized DM. 24 hours post-seeding, hESC-RPE cell attachment and initial proliferation rate over the denuded DM were higher than hESC-RPE cells cultured on tissue culture inserts. On the new matrix, hESC-RPE cells succeeded in forming an intact monolayer with mature tight junctions. The resulting cell culture showed characteristic RPE cell morphology and proper protein localization. Gene expression analysis and VEGF secretion demonstrate DM provides supportive scaffolding and inductive properties to enhance hESC-RPE cells maturation. Decellularized DM was shown to be capable of sustaining hESC-RPE cells culture, thus confirming to be potentially a suitable candidate for retinal cell therapy.
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Affiliation(s)
- Elena Daniele
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Veneto Eye Bank Foundation, Venice, Italy
- * E-mail:
| | | | - Noor Ahmed Hussain
- Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom
| | | | | | | | - Brian McArdle
- The Eye-Bank for Sight Restoration, Inc., New York City, New York, United States of America
| | - Nicolò Rassu
- Ophthalmic Unit, Ospedale dell’Angelo, Venice, Italy
| | - Marco Mura
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Francesco Parmeggiani
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- ERN-EYE Network - Center for Retinitis Pigmentosa of Veneto Region, Camposampiero Hospital, Padua, Italy
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15
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Ali MA, Aswathy KA, Munuswamy-Ramanujam G, Jaisankar V. Pyridine and isoxazole substituted 3-formylindole-based chitosan Schiff base polymer: Antimicrobial, antioxidant and in vitro cytotoxicity studies on THP-1 cells. Int J Biol Macromol 2023; 225:1575-1587. [PMID: 36436605 DOI: 10.1016/j.ijbiomac.2022.11.214] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 11/15/2022] [Accepted: 11/21/2022] [Indexed: 11/27/2022]
Abstract
This paper presents the synthesis of two new chitosan Schiff base (CSB) polymers, namely, 2PCT and 4MCT based on pyridin-2-ylmethyl-1H-indole-3-carbaldehyde and 1-(4-methyl-3,5-dimethylisoxazole)-1H-indole-3-carbaldehyde with chitosan (CT). The structural features of CSB polymers were confirmed by Fourier-transform infrared (FTIR) and proton nuclear magnetic resonance (1H NMR) spectroscopy and their antimicrobial activity was evaluated against Staphylococcus aureus, Escherichia coli and Candida albicans. The antioxidant studies found that both 2PCT and 4MCT presented significant free radical scavenging activity with IC50 at 169.01 and 372.84 μg/mL, respectively. The cell viability results obtained from in vitro cytotoxicity studies performed using human monocyte leukemia (THP-1) cells were found to be 75.6 ± 0.25 % and 79.1 ± 1.5 % for 2PCT and 4MCT, respectively, at a concentration of 10 mg/mL. Flow cytometry analysis demonstrated the reducing ability of CSB polymers on intracellular reactive oxygen species (ROS) in THP-1 cells. The overall results of antioxidant activity, in vitro biocompatibility and ability to reduce the intracellular ROS production emphasized that the CSB polymers prepared could serve as a potential biomaterial in biomedical applications, such as wound treatment process.
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Affiliation(s)
- M Ameer Ali
- Department of Chemistry, The New College (Autonomous), Chennai 600014, Tamil Nadu, India; Department of Chemistry, Presidency College (Autonomous), Chennai 600005, Tamil Nadu, India
| | - K A Aswathy
- Division of Molecular Biology and Immuno Biology, IIISM, SRM IST, Kattankulathur, 603203, Tamil Nadu, India
| | - Ganesh Munuswamy-Ramanujam
- Division of Molecular Biology and Immuno Biology, IIISM, SRM IST, Kattankulathur, 603203, Tamil Nadu, India; Department of Chemistry, Faculty of Science & Humanities, SRM IST, Kattankulathur, 603203, Tamil Nadu, India
| | - V Jaisankar
- Department of Chemistry, Presidency College (Autonomous), Chennai 600005, Tamil Nadu, India.
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Alka, Verma A, Mishra N, Singh N, Singh P, Nisha R, Pal RR, Saraf SA. Polymeric Gel Scaffolds and Biomimetic Environments for Wound Healing. Curr Pharm Des 2023; 29:3221-3239. [PMID: 37584354 DOI: 10.2174/1381612829666230816100631] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 06/16/2023] [Accepted: 07/14/2023] [Indexed: 08/17/2023]
Abstract
Infected wounds that do not heal are a worldwide problem that is worsening, with more people dying and more money being spent on care. For any disease to be managed effectively, its root cause must be addressed. Effective wound care becomes a bigger problem when various traditional wound healing methods and products may not only fail to promote good healing. Still, it may also hinder the healing process, causing wounds to stay open longer. Progress in tissue regeneration has led to developing three-dimensional scaffolds (3D) or constructs that can be leveraged to facilitate cell growth and regeneration while preventing infection and accelerating wound healing. Tissue regeneration uses natural and fabricated biomaterials that encourage the growth of tissues or organs. Even though the clinical need is urgent, the demand for polymer-based therapeutic techniques for skin tissue abnormalities has grown quickly. Hydrogel scaffolds have become one of the most imperative 3D cross-linked scaffolds for tissue regeneration because they can hold water perfectly and are porous, biocompatible, biodegradable, and biomimetic. For damaged organs or tissues to heal well, the porosity topography of the natural extracellular matrix (ECM) should be imitated. This review details the scaffolds that heal wounds and helps skin tissue to develop. After a brief overview of the bioactive and drug-loaded polymeric hydrogels, the discussion moves on to how the scaffolds are made and what they are made of. It highlights the present uses of in vitro and in-vivo employed biomimetic scaffolds. The prospects of how well bioactiveloaded hydrogels heal wounds and how nanotechnology assists in healing and regeneration have been discussed.
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Affiliation(s)
- Alka
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University Lucknow (A Central University), Uttar Pradesh, Vidya Vihar, Raebareli Road, Lucknow, 226025, Uttar Pradesh, India
| | - Abhishek Verma
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University Lucknow (A Central University), Uttar Pradesh, Vidya Vihar, Raebareli Road, Lucknow, 226025, Uttar Pradesh, India
| | - Nidhi Mishra
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University Lucknow (A Central University), Uttar Pradesh, Vidya Vihar, Raebareli Road, Lucknow, 226025, Uttar Pradesh, India
| | - Neelu Singh
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University Lucknow (A Central University), Uttar Pradesh, Vidya Vihar, Raebareli Road, Lucknow, 226025, Uttar Pradesh, India
| | - Priya Singh
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University Lucknow (A Central University), Uttar Pradesh, Vidya Vihar, Raebareli Road, Lucknow, 226025, Uttar Pradesh, India
| | - Raquibun Nisha
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University Lucknow (A Central University), Uttar Pradesh, Vidya Vihar, Raebareli Road, Lucknow, 226025, Uttar Pradesh, India
| | - Ravi Raj Pal
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University Lucknow (A Central University), Uttar Pradesh, Vidya Vihar, Raebareli Road, Lucknow, 226025, Uttar Pradesh, India
| | - Shubhini A Saraf
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University Lucknow (A Central University), Uttar Pradesh, Vidya Vihar, Raebareli Road, Lucknow, 226025, Uttar Pradesh, India
- National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, Bijnor-Sisendi Road, Sarojini Nagar, Lucknow, 226002, Uttar Pradesh, India
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Zhang Y, Huo M, Wang Y, Xiao L, Wu J, Ma Y, Zhang D, Lang X, Wang X. A tailored bioactive 3D porous poly(lactic-acid)-exosome scaffold with osteo-immunomodulatory and osteogenic differentiation properties. J Biol Eng 2022; 16:22. [PMID: 35996115 PMCID: PMC9394013 DOI: 10.1186/s13036-022-00301-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 08/08/2022] [Indexed: 11/10/2022] Open
Abstract
Polylactic acid (PLA) is a versatile and biodegradable scaffold widely used in biomedical fields to repair tissue defects. Exosomes derived from mesenchymal stem cells (MSCs) are nano-sized extracellular vesicles, which play an important role in tissue engineering in recent years. The primary focus of this study was to develop a bioactive 3D PLA scaffold using exosome-based strategy to improve its osteogenic and immunoregulatory potential. We firstly successfully isolated MSC-derived exosomes (MSC-Exo). Morphological analysis revealed that MSC-Exo exhibits a typical cup-shaped morphology with high expression of exosomal marker CD63. MSC-Exo internalization into recipient cells were also investigated using flow cytometry and confocal laser scanning microscopy. Porous 3D PLA scaffold coated MSC-Exo were used for immunoregulatory and osteogenic testing. Exosomes released from 3D PLA scaffold were validated in RAW264.7 and hBMSCs. The cell proliferation and live/dead assay indicated high biocompatibility for PLA-Exo scaffold. Additionally, PLA-Exo scaffold could reduce the pro-inflammatory marker expression and reactive oxygen species (ROS) production, indicating potential immunoregulatory potential. It is also confirmed that PLA-Exo scaffold could potentiate osteogenic differentiation in the osteogenesis assay. In conclusion, our results demonstrate this bioactive 3D-printed PLA scaffolds with MSC-Exo modification holds immunoregulatory potential and favor osteogenic differentiation, thus having potential applications in bone tissue regeneration.
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Affiliation(s)
- Yi Zhang
- Department of Hygiene Toxicology, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Mengjie Huo
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Yi Wang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Lan Xiao
- School of Mechanical, Medical & Process Engineering, Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, 4000, Australia.,Australia China Centre for Tissue Engineering and Regenerative Medicine, Kelvin Grove, Brisbane, Queensland, 4059, Australia
| | - Jianmei Wu
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Yaping Ma
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Dingmei Zhang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Xuemei Lang
- Department of Pre-hospital Emergency, Central Hospital of Chongqing University / Chongqing Emergency Medical Center, Chongqing, Chongqing, 400014, China.
| | - Xin Wang
- Department of Hygiene Toxicology, Zunyi Medical University, Zunyi, 563000, Guizhou, China. .,Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China. .,School of Mechanical, Medical & Process Engineering, Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, 4000, Australia. .,Australia China Centre for Tissue Engineering and Regenerative Medicine, Kelvin Grove, Brisbane, Queensland, 4059, Australia.
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19
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Solarte David VA, Güiza-Argüello VR, Arango-Rodríguez ML, Sossa CL, Becerra-Bayona SM. Decellularized Tissues for Wound Healing: Towards Closing the Gap Between Scaffold Design and Effective Extracellular Matrix Remodeling. Front Bioeng Biotechnol 2022; 10:821852. [PMID: 35252131 PMCID: PMC8896438 DOI: 10.3389/fbioe.2022.821852] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 01/28/2022] [Indexed: 12/27/2022] Open
Abstract
The absence or damage of a tissue is the main cause of most acute or chronic diseases and are one of the appealing challenges that novel therapeutic alternatives have, in order to recover lost functions through tissue regeneration. Chronic cutaneous lesions are the most frequent cause of wounds, being a massive area of regenerative medicine and tissue engineering to have efforts to develop new bioactive medical products that not only allow an appropriate and rapid healing, but also avoid severe complications such as bacterial infections. In tissue repair and regeneration processes, there are several overlapping stages that involve the synergy of cells, the extracellular matrix (ECM) and biomolecules, which coordinate processes of ECM remodeling as well as cell proliferation and differentiation. Although these three components play a crucial role in the wound healing process, the ECM has the function of acting as a biological platform to permit the correct interaction between them. In particular, ECM is a mixture of crosslinked proteins that contain bioactive domains that cells recognize in order to promote migration, proliferation and differentiation. Currently, tissue engineering has employed several synthetic polymers to design bioactive scaffolds to mimic the native ECM, by combining biopolymers with growth factors including collagen and fibrinogen. Among these, decellularized tissues have been proposed as an alternative for reconstructing cutaneous lesions since they maintain the complex protein conformation, providing the required functional domains for cell differentiation. In this review, we present an in-depth discussion of different natural matrixes recently employed for designing novel therapeutic alternatives for treating cutaneous injuries, and overview some future perspectives in this area.
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Affiliation(s)
- Víctor Alfonso Solarte David
- Program of Medicine, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
- Program of Biomedical Engineering, Faculty of Engineering, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
| | - Viviana Raquel Güiza-Argüello
- Metallurgical Engineering and Materials Science Department, Faculty of Physicochemical Engineering, Universidad Industrial de Santander, Bucaramanga, Colombia
| | - Martha L. Arango-Rodríguez
- Multi-tissue Bank and Advanced Therapy Center, Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle, Floridablanca, Colombia
| | - Claudia L. Sossa
- Program of Medicine, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
- Multi-tissue Bank and Advanced Therapy Center, Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle, Floridablanca, Colombia
| | - Silvia M. Becerra-Bayona
- Program of Medicine, Faculty of Health Sciences, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia
- *Correspondence: Silvia M. Becerra-Bayona,
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Fan F, Saha S, Hanjaya-Putra D. Biomimetic Hydrogels to Promote Wound Healing. Front Bioeng Biotechnol 2021; 9:718377. [PMID: 34616718 PMCID: PMC8488380 DOI: 10.3389/fbioe.2021.718377] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/13/2021] [Indexed: 01/13/2023] Open
Abstract
Wound healing is a common physiological process which consists of a sequence of molecular and cellular events that occur following the onset of a tissue lesion in order to reconstitute barrier between body and external environment. The inherent properties of hydrogels allow the damaged tissue to heal by supporting a hydrated environment which has long been explored in wound management to aid in autolytic debridement. However, chronic non-healing wounds require added therapeutic features that can be achieved by incorporation of biomolecules and supporting cells to promote faster and better healing outcomes. In recent decades, numerous hydrogels have been developed and modified to match the time scale for distinct stages of wound healing. This review will discuss the effects of various types of hydrogels on wound pathophysiology, as well as the ideal characteristics of hydrogels for wound healing, crosslinking mechanism, fabrication techniques and design considerations of hydrogel engineering. Finally, several challenges related to adopting hydrogels to promote wound healing and future perspectives are discussed.
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Affiliation(s)
- Fei Fan
- Bioengineering Graduate Program, Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN, United States
| | - Sanjoy Saha
- Bioengineering Graduate Program, Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN, United States
| | - Donny Hanjaya-Putra
- Bioengineering Graduate Program, Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN, United States
- Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN, United States
- Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, United States
- Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, IN, United States
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21
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Miricescu D, Badoiu SC, Stanescu-Spinu II, Totan AR, Stefani C, Greabu M. Growth Factors, Reactive Oxygen Species, and Metformin-Promoters of the Wound Healing Process in Burns? Int J Mol Sci 2021; 22:ijms22179512. [PMID: 34502429 PMCID: PMC8431501 DOI: 10.3390/ijms22179512] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 08/26/2021] [Accepted: 08/30/2021] [Indexed: 12/19/2022] Open
Abstract
Burns can be caused by various factors and have an increased risk of infection that can seriously delay the wound healing process. Chronic wounds caused by burns represent a major health problem. Wound healing is a complex process, orchestrated by cytokines, growth factors, prostaglandins, free radicals, clotting factors, and nitric oxide. Growth factors released during this process are involved in cell growth, proliferation, migration, and differentiation. Reactive oxygen species are released in acute and chronic burn injuries and play key roles in healing and regeneration. The main aim of this review is to present the roles of growth factors, reactive oxygen species, and metformin in the healing process of burn injuries.
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Affiliation(s)
- Daniela Miricescu
- Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania; (D.M.); (A.R.T.); (M.G.)
| | - Silviu Constantin Badoiu
- Department of Anatomy and Embriology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania
- Department of Plastic and Reconstructive Surgery, Life Memorial Hospital, 365 Grivitei Street, 010719 Bucharest, Romania
- Correspondence: (S.C.B.); (I.-I.S.-S.)
| | - Iulia-Ioana Stanescu-Spinu
- Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania; (D.M.); (A.R.T.); (M.G.)
- Correspondence: (S.C.B.); (I.-I.S.-S.)
| | - Alexandra Ripszky Totan
- Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania; (D.M.); (A.R.T.); (M.G.)
| | - Constantin Stefani
- Department of Family Medicine and Clinical Base, Dr. Carol Davila Central Military Emergency University Hospital, 010825 Bucharest, Romania;
| | - Maria Greabu
- Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania; (D.M.); (A.R.T.); (M.G.)
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Versatile Use of Chitosan and Hyaluronan in Medicine. Molecules 2021; 26:molecules26041195. [PMID: 33672365 PMCID: PMC7926841 DOI: 10.3390/molecules26041195] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/17/2021] [Accepted: 02/20/2021] [Indexed: 12/22/2022] Open
Abstract
Chitosan is industrially acquired by the alkaline N-deacetylation of chitin. Chitin belongs to the β-N-acetyl-glucosamine polymers, providing structure, contrary to α-polymers, which provide food and energy. Another β-polymer providing structure is hyaluronan. A lot of studies have been performed on chitosan to explore its industrial use. Since chitosan is biodegradable, non-toxic, bacteriostatic, and fungistatic, it has numerous applications in medicine. Hyaluronan, one of the major structural components of the extracellular matrix in vertebrate tissues, is broadly exploited in medicine as well. This review summarizes the main areas where these two biopolymers have an impact. The reviewed areas mostly cover most medical applications, along with non-medical applications, such as cosmetics.
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