1
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Wang H, Wu S, Bai X, Pan D, Ning Y, Wang C, Guo L, Guo J, Gu Y. Mesenchymal Stem Cell-Derived Exosomes Hold Promise in the Treatment of Diabetic Foot Ulcers. Int J Nanomedicine 2025; 20:5837-5857. [PMID: 40351704 PMCID: PMC12065540 DOI: 10.2147/ijn.s516533] [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: 01/09/2025] [Accepted: 04/11/2025] [Indexed: 05/14/2025] Open
Abstract
Diabetic foot ulcers (DFU) represent one of the most common side effects of diabetes, significantly impacting patients' quality of life and imposing considerable financial burdens on families and society at large. Despite advancements in therapies targeting lower limb revascularization and various medications and dressings, outcomes for patients with severe lesions remain limited. A recent breakthrough in DFU treatment stems from the development of mesenchymal stem cells (MSCs). MSCs have shown promising results in treating various diseases and skin wounds due to their ability for multidirectional differentiation and immunomodulation. Recent studies highlight that MSCs primarily repair tissue through their paracrine activities, with exosomes playing a crucial role as the main biologically active components. These exosomes transport proteins, mRNA, DNA, and other substances, facilitating DFU treatment through immunomodulation, antioxidant effects, angiogenesis promotion, endothelial cell migration and proliferation, and collagen remodeling. Mesenchymal stem cell-derived exosomes (MSC-Exo) not only deliver comparable therapeutic effects to MSCs but also mitigate adverse reactions like immune rejection associated with MSCs transplantation. This article provides an overview of DFU pathophysiology and explores the mechanisms and research progress of MSC-Exo in DFU therapy.
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Affiliation(s)
- Hui Wang
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Sensen Wu
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Xinyu Bai
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China
| | - Dikang Pan
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Yachan Ning
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Cong Wang
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Lianrui Guo
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Jianming Guo
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
| | - Yongquan Gu
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China
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2
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Liu L, Liu W, Han Z, Shan Y, Xie Y, Wang J, Qi H, Xu Q. Extracellular Vesicles-in-Hydrogel (EViH) targeting pathophysiology for tissue repair. Bioact Mater 2025; 44:283-318. [PMID: 39507371 PMCID: PMC11539077 DOI: 10.1016/j.bioactmat.2024.10.017] [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: 04/06/2024] [Revised: 10/08/2024] [Accepted: 10/17/2024] [Indexed: 11/08/2024] Open
Abstract
Regenerative medicine endeavors to restore damaged tissues and organs utilizing biological approaches. Utilizing biomaterials to target and regulate the pathophysiological processes of injured tissues stands as a crucial method in propelling this field forward. The Extracellular Vesicles-in-Hydrogel (EViH) system amalgamates the advantages of extracellular vesicles (EVs) and hydrogels, rendering it a prominent biomaterial in regenerative medicine with substantial potential for clinical translation. This review elucidates the development and benefits of the EViH system in tissue regeneration, emphasizing the interaction and impact of EVs and hydrogels. Furthermore, it succinctly outlines the pathophysiological characteristics of various types of tissue injuries such as wounds, bone and cartilage injuries, cardiovascular diseases, nerve injuries, as well as liver and kidney injuries, underscoring how EViH systems target these processes to address related tissue damage. Lastly, it explores the challenges and prospects in further advancing EViH-based tissue regeneration, aiming to impart a comprehensive understanding of EViH. The objective is to furnish a thorough overview of EViH in enhancing regenerative medicine applications and to inspire researchers to devise innovative tissue engineering materials for regenerative medicine.
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Affiliation(s)
- Lubin Liu
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Wei Liu
- Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266003, China
| | - Zeyu Han
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Yansheng Shan
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Yutong Xie
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Jialu Wang
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
| | - Hongzhao Qi
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, China
| | - Quanchen Xu
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
- School of Stomatology, Qingdao University, Qingdao, 266023, China
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3
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Kumar V, Sundramoorthy AK. Potential of Nature-derived Biopolymers for Oral Applications- A Mini-Review. Mini Rev Med Chem 2025; 25:529-538. [PMID: 39757671 DOI: 10.2174/0113895575359305241218113847] [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: 09/21/2024] [Revised: 11/22/2024] [Accepted: 11/26/2024] [Indexed: 01/07/2025]
Abstract
In recent years, there has been a growing emphasis on the "back-to-nature" movement, which has brought biopolymers derived from natural sources into the spotlight. These biopolymers are gaining attention for their versatile surface-active properties, anti-adhesive capabilities, excellent biocompatibility, non-toxicity, biodegradability, and antimicrobial effectiveness against a wide range of oral microorganisms, including both bacteria and fungi. Researchers have been actively modifying these eco-friendly, nature-based biopolymers to enhance their interaction with surrounding cells and tissues, improving their performance in vivo. This has led to innovative applications in areas such as surface coatings, controlled drug delivery, tissue repair, and dental implant devices. These advancements hold the potential to pave the way for the development of novel drug delivery systems with enhanced therapeutic properties, ultimately supporting the creation of innovative formulations for clinical use. This review aims to provide an up-to-date overview of recent developments, explore potential future directions, and highlight the promising applications of nature-derived biopolymers in oral healthcare.
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Affiliation(s)
- Vijayalakshmi Kumar
- Department of Chemistry (SFS), Madras Christian College, East Tambaram, Chennai, India
| | - Ashok K Sundramoorthy
- Centre for Nanobiosensors, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, 600017, India
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4
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Esmaeili A, Noorkhajavi G, Soleimani M, Farsinezhad H, Bagheri-Mohammadi S, Keshel SH. Application of exosomes for the regeneration of skin wounds: Principles, recent applications and limitations. Tissue Cell 2024; 91:102611. [PMID: 39550901 DOI: 10.1016/j.tice.2024.102611] [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: 10/30/2024] [Accepted: 11/07/2024] [Indexed: 11/19/2024]
Abstract
In the medical field, wound healing poses significant challenges due to its complexity and time-consuming nature. Cell-free wound repair, notably the utilization of exosomes (EXOs), has made significant progress in recent years. Urine, saliva, umbilical cord, blood, mesenchymal stem cells and breast milk cells can be used to extract and purify EXOs, which are Nano-sized lipid bilayer vesicles. Besides their relatively little toxicity, non-specific immunogenicity and excellent biocompatibility, EXOs also contain bioactive molecules such as proteins, lipids, microRNAs (miRNAs), and messenger RNAs (mRNAs). Their bioactive compounds have anti-inflammatory properties and can speed up wound healing. Various medicinal agents can also be contained within the EXOs. This review briefly provides new information on the different aspects of EXOs and evaluate the application of EXOs as a promising therapy in the regeneration of skin wounds in recent pre-clinical and clinical studies.
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Affiliation(s)
- Ali Esmaeili
- Student Research Committee, Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ghasem Noorkhajavi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; Drug Applied Research Center and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoud Soleimani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hana Farsinezhad
- Drug Applied Research Center and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeid Bagheri-Mohammadi
- Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran; Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Saeed Heidari Keshel
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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5
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Zhang S, Lu X, Chen J, Xiong S, Cui Y, Wang S, Yue C, Han Q, Yang B. Promotion of angiogenesis and suppression of inflammatory response in skin wound healing using exosome-loaded collagen sponge. Front Immunol 2024; 15:1511526. [PMID: 39669582 PMCID: PMC11634875 DOI: 10.3389/fimmu.2024.1511526] [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: 10/15/2024] [Accepted: 11/13/2024] [Indexed: 12/14/2024] Open
Abstract
Effectively promoting skin wound healing remains a significant challenge in the medical field. Although stem cell-derived exosomes show potential in tissue regeneration, their local delivery and sustained release face challenges. To address these issues, we developed a collagen sponge based on type I and recombinant humanized type III collagen. Our study confirmed that exosomes were successfully loaded onto the sponge (sponge-Exo) and the sponge-Exo gradually released exosomes into the local milieu. The sponge-Exo played a crucial role in promoting the transition of macrophages from an inflammatory M1 phenotype to a regenerative M2 phenotype. Moreover, it enhanced the migration and proliferation of HDFs and promoted angiogenesis in HUVECs. Additionally, our findings revealed that the sponge-Exo accelerated wound healing by suppressing inflammatory response and stimulating angiogenesis in a rat full-thickness skin wounds model. Next generation sequencing (NGS) was used to explore the underlying mechanism of wound healing, and the results showed that the miRNAs (hsa-miR-21-5p and hsa-miR-29a-5p) associated with wound healing in exosomes were significantly up-regulated. These results highlight the remarkable effects of sponge-Exo on macrophage transformation, cell migration, proliferation and angiogenesis, which provide a potential prospect for the application in the field of skin wound healing.
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Affiliation(s)
- Siqi Zhang
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Xugang Lu
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Jun Chen
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Shibing Xiong
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Yifan Cui
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Simeng Wang
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
| | - Chongxia Yue
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
- NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial & Institute of Regulatory Science for Medical Devices & NMPA Research Base of Regulatory Science for Medical Devices, Sichuan University, Chengdu, China
| | - Qianqian Han
- Medical Device Testing Institute, National Institutes for Food and Drug Control, Beijing, China
| | - Bangcheng Yang
- Engineering Research Center in Biomaterials, Sichuan University, Chengdu, China
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6
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Ghasempour A, Dehghan H, Mahmoudi M, Lavi Arab F. Biomimetic scaffolds loaded with mesenchymal stem cells (MSCs) or MSC-derived exosomes for enhanced wound healing. Stem Cell Res Ther 2024; 15:406. [PMID: 39522032 PMCID: PMC11549779 DOI: 10.1186/s13287-024-04012-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
Since wound healing is one of the most important medical challenges and common dressings have not been able to manage this challenge well today, efforts have been increased to achieve an advanced dressing. Mesenchymal stem cells and exosomes derived from them have shown high potential in healing and regenerating wounds due to their immunomodulatory, anti-inflammatory, immunosuppressive, and high regenerative capacities. However, challenges such as the short life of these cells, the low durability of these cells in the wound area, and the low stability of exosomes derived from them have resulted in limitations in their use for wound healing. Nowadays, different scaffolds are considered suitable biomaterials for wound healing. These scaffolds are made of natural or synthetic polymers and have shown promising potential for an ideal dressing that does not have the disadvantages of common dressings. One of the strategies that has attracted much attention today is using these scaffolds for seeding and delivering MSCs and their exosomes. This combined strategy has shown a high potential in enhancing the shelf life of cells and increasing the stability of exosomes. In this review, the combination of different scaffolds with different MSCs or their exosomes for wound healing has been comprehensively discussed.
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Affiliation(s)
- Alireza Ghasempour
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamideh Dehghan
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Mahmoud Mahmoudi
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fahimeh Lavi Arab
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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7
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Zhuang X, Zhu H, Wang F, Hu X. Revolutionizing wild silk fibers: Ultrasound enhances structure, properties, and regenerability of protein biomaterials in ionic liquids. ULTRASONICS SONOCHEMISTRY 2024; 109:107018. [PMID: 39128406 DOI: 10.1016/j.ultsonch.2024.107018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/17/2024] [Accepted: 08/05/2024] [Indexed: 08/13/2024]
Abstract
Ultrasound-assisted regulation of biomaterial properties has attracted increasing attention due to the unique reaction conditions induced by ultrasound cavitation. In this study, we explored the fabrication of wild tussah silk nanofiber membranes via ultrasound spray spinning from an ionic liquid system, characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), atomic force microscopy (AFM), water contact angle, cytocompatibility tests, and enzymatic degradation studies. We investigated the effects of ultrasound propagation in an ionic liquid on the morphology, structure, thermal and mechanical properties, surface hydrophilicity, biocompatibility, and biodegradability of the fabricated fibers. The results showed that as ultrasound treatment time increased from 0 to 60 min, the regenerated silk fiber diameter decreased by 0.97 μm and surface area increased by 30.44 μm2, enhancing the fiber surface smoothness and uniformity. Ultrasound also promoted the rearrangement of protein molecular chains and transformation of disordered protein structures into β-sheets, increasing the β-sheet content to 54.32 %, which significantly improved the materials' thermal stability (with decomposition temperatures rising to 256.38 °C) and mechanical properties (elastic modulus reaching 0.75 GPa). In addition, hydrophilicity, cytocompatibility, and biodegradability of the fiber membranes all improved with longer ultrasound exposure, highlighting the potential of ultrasound technology in advancing the properties of natural biopolymers for applications in sustainable materials science and tissue regeneration.
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Affiliation(s)
- Xincheng Zhuang
- Center of Analysis and Testing, Nanjing Normal University, Nanjing 210023, China; School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Haomiao Zhu
- School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Fang Wang
- Center of Analysis and Testing, Nanjing Normal University, Nanjing 210023, China; School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
| | - Xiao Hu
- Department of Physics and Astronomy, Rowan University, Glassboro, NJ 08028, USA; Department of Biological and Biomedical Sciences, Rowan University, Glassboro, NJ 08028, USA.
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8
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Britton D, Almanzar D, Xiao Y, Shih HW, Legocki J, Rabbani P, Montclare JK. Exosome Loaded Protein Hydrogel for Enhanced Gelation Kinetics and Wound Healing. ACS APPLIED BIO MATERIALS 2024; 7:5992-6000. [PMID: 39173187 PMCID: PMC11409212 DOI: 10.1021/acsabm.4c00569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 08/15/2024] [Accepted: 08/16/2024] [Indexed: 08/24/2024]
Abstract
Exosomes are being increasingly explored in biomedical research for wound healing applications. Exosomes can improve blood circulation and endocrine signaling, resulting in enhanced cell regeneration. However, exosome treatments suffer from low retention and bioavailability of exosomes at the wound site. Hydrogels are a popular tool for drug delivery due to their ability to encapsulate drugs in their network and allow for targeted release. Recently, hydrogels have proven to be an effective method to provide increased rates of wound healing when combined with exosomes that can be applied noninvasively. We have designed a series of single-domain protein-based hydrogels capable of physical cross-linking and upper critical solution temperature (UCST) behavior. Hydrogel variant Q5, previously designed with improved UCST behavior and a significantly enhanced gelation rate, is selected as a candidate for encapsulation release of exosomes dubbed Q5Exo. Q5Exo exhibits low critical gelation times and significant decreases in wound healing times in a diabetic mouse wound model showing promise as an exosome-based drug delivery tool and for future hybrid, noninvasive protein-exosome design.
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Affiliation(s)
- Dustin Britton
- Department
of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, Brooklyn, New York 11201, United States
| | - Dianny Almanzar
- Hansjörg
Wyss Department of Plastic Surgery, New
York University School of Medicine, New York, New York, 10016, United States
| | - Yingxin Xiao
- Department
of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, Brooklyn, New York 11201, United States
| | - Hao-Wei Shih
- Department
of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, Brooklyn, New York 11201, United States
| | - Jakub Legocki
- Department
of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, Brooklyn, New York 11201, United States
| | - Piul Rabbani
- Hansjörg
Wyss Department of Plastic Surgery, New
York University School of Medicine, New York, New York, 10016, United States
| | - Jin Kim Montclare
- Department
of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, Brooklyn, New York 11201, United States
- Bernard
and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, New York, 10016, United
States
- Department
of Chemistry, New York University, New York, New York, 10012, United
States
- Department
of Biomaterials, New York University College
of Dentistry, New York, New York, 10010, United States
- Department
of Biomedical Engineering, New York University, New York, New York 11201, United States
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9
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Pratiwi FW, Thomas RT, Karzarjeddi M, Sarpola M, Miinalainen I, Makieieva O, Jokipii-Lukkari S, Elbuken C, Oksman K, Vainio SJ, Liimatainen H. Scalable Purification, Storage, and Release of Plant-Derived Nanovesicles for Local Therapy Using Nanostructured All-Cellulose Composite Membranes. Biomacromolecules 2024; 25:5847-5859. [PMID: 39190019 DOI: 10.1021/acs.biomac.4c00535] [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: 08/28/2024]
Abstract
Plant-derived nanovesicles such as bilberries nanovesicles (BNVs) show immense promise as next-generation biotherapeutics and functional food ingredients; however, their isolation, purification, and storage on a large scale remain a challenge. In this study, biocompatible and nanostructured composite all-cellulose membranes are introduced as a scalable and straightforward approach to the isolation of BNV. The membranes consisting of a cellulose acetate matrix infused with anionic or cationic nanocelluloses promoted selective capture of BNVs through electrostatic and size-exclusion-mediated depth filtration. Furthermore, the surface of the composite membrane acted as a storage matrix for BNVs, ensuring their prolonged stability at 4 °C. The BNVs stored in the membrane could be promptly released through elution assisted by low-pressure vacuum filtration or diffusion in liquid media. The morphology, bioactivity, and stability of the extracted BNVs were preserved, and the release rate of BNVs in different cell cultures could be regulated, facilitating their use for local therapy. Consequently, this approach paves the way for the scalable production, purification, and storage of nanovesicles and advances their use in biotherapeutics and functional foods.
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Affiliation(s)
- Feby W Pratiwi
- Laboratory of Developmental Biology, Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland
- Kvantum Institute, University of Oulu, 90014 Oulu, Finland
| | - Reny T Thomas
- Division of Materials Science, Department of Engineering Sciences and Mathematics, Luleå University of Technology, SE-97187 Luleå, Sweden
| | - Mohammad Karzarjeddi
- Fiber and Particle Engineering Research Unit, University of Oulu, P.O. Box 4300, FI-90014 Oulu, Finland
| | - Marjaana Sarpola
- Laboratory of Developmental Biology, Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland
| | - Ilkka Miinalainen
- Biocenter Oulu, Department of Pathology, Oulu University Hospital, 90220 Oulu, Finland
| | - Olha Makieieva
- Laboratory of Developmental Biology, Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland
| | - Soile Jokipii-Lukkari
- Ecology and Genetics Department, University of Oulu, P.O. Box 8000, FI-90014 Oulu, Finland
| | - Caglar Elbuken
- Micro-/Nanofluidics and Biosensor Research Group, University of Oulu, P.O. Box 5400, FI-90014 Oulu, Finland
- Kvantum Institute, University of Oulu, 90014 Oulu, Finland
| | - Kristiina Oksman
- Division of Materials Science, Department of Engineering Sciences and Mathematics, Luleå University of Technology, SE-97187 Luleå, Sweden
- WWSC Wallenberg Wood Science Center, Luleå University of Technology, SE 97187 Luleå, Sweden
- Department of Mechanical & Industrial Engineering (MIE), University of Toronto, Toronto, Ontario M5S 3G8, Canada
| | - Seppo J Vainio
- Laboratory of Developmental Biology, Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland
- Kvantum Institute, University of Oulu, 90014 Oulu, Finland
| | - Henrikki Liimatainen
- Fiber and Particle Engineering Research Unit, University of Oulu, P.O. Box 4300, FI-90014 Oulu, Finland
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10
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Doshi RB, Vakil D, Molley TG, Islam MS, Kilian KA, Cunningham C, Sidhu KS. Mesenchymal stem cell-secretome laden photopolymerizable hydrogels for wound healing. J Biomed Mater Res A 2024; 112:1484-1493. [PMID: 38487991 DOI: 10.1002/jbm.a.37697] [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: 07/12/2023] [Revised: 02/17/2024] [Accepted: 02/21/2024] [Indexed: 07/12/2024]
Abstract
Mesenchymal stem cell-derived secretome represents an emerging acellular therapeutic which possess significant opportunity for clinical applications due to its anti-inflammatory, immunomodulatory, and wound healing properties. However, maintaining therapeutic efficacy and ensuring stability of cell-based products is challenging, requiring a robust delivery method. Therefore, we designed a hydrogel-based scaffold loaded with CK Cell Technologies' proprietary Mesenchymal stem cell-secretome for controlled release treatment of acute and chronic wounds. We incorporated both conditioned media (CM) and extracellular vesicles (EVs) into gelatin methacryloyl (GelMA) hydrogels and demonstrated how we can tune the diffusive release of the EVs from them. To demonstrate viability of the approach, we developed a wound healing scratch assay where we see in situ release of CM and EVs promote enhanced migration of human dermal fibroblasts (hDFs). We see the colocalization of these EVs in the fibroblasts using fluorescent microscopy. Finally, as a surrogate for in vivo neovascularization, we conducted an in vitro tube formation assay for the MSC-secretome using matrigel-embedded human microvascular endothelial cells. By adding CM and EVs, we observe an increase in tubulogenesis. Collectively, our data demonstrates by tuning the GelMA properties, we can influence the controlled release of the MSC-secretome for a wound dressing and bandage application for chronic and acute wounds.
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Affiliation(s)
- Riddhesh B Doshi
- R & D, CK Cell Technologies Pty Ltd, Sydney, New South Wales, Australia
- School of Chemistry, University of New South Wales (UNSW), Sydney, New South Wales, Australia
| | - Devashree Vakil
- R & D, CK Cell Technologies Pty Ltd, Sydney, New South Wales, Australia
| | - Thomas G Molley
- School of Materials Science and Engineering, University of New South Wales (UNSW), Sydney, New South Wales, Australia
| | - Md Shariful Islam
- School of Materials Science and Engineering, University of New South Wales (UNSW), Sydney, New South Wales, Australia
| | - Kristopher A Kilian
- School of Chemistry, University of New South Wales (UNSW), Sydney, New South Wales, Australia
- School of Materials Science and Engineering, University of New South Wales (UNSW), Sydney, New South Wales, Australia
| | - Corey Cunningham
- R & D, CK Cell Technologies Pty Ltd, Sydney, New South Wales, Australia
| | - Kuldip S Sidhu
- R & D, CK Cell Technologies Pty Ltd, Sydney, New South Wales, Australia
- Faculty of Medicine, University of New South Wales (UNSW), Sydney, New South Wales, Australia
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11
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Jha S, Akula B, Enyioma H, Novak M, Amin V, Liang H. Biodegradable Biobased Polymers: A Review of the State of the Art, Challenges, and Future Directions. Polymers (Basel) 2024; 16:2262. [PMID: 39204482 PMCID: PMC11359911 DOI: 10.3390/polym16162262] [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: 05/30/2024] [Revised: 07/24/2024] [Accepted: 08/06/2024] [Indexed: 09/04/2024] Open
Abstract
Biodegradable biobased polymers derived from biomass (such as plant, animal, marine, or forestry material) show promise in replacing conventional petrochemical polymers. Research and development have been conducted for decades on potential biodegradable biobased polymers such as polylactic acid (PLA), polyhydroxyalkanoates (PHAs), and succinate polymers. These materials have been evaluated for practicality, cost, and production capabilities as limiting factors in commercialization; however, challenges, such as the environmental limitations on the biodegradation rates for biodegradable biobased polymer, need to be addressed. This review provides a history and overview of the current development in the synthesis process and properties of biodegradable biobased polymers, along with a techno-commercial analysis and discussion on the environmental impacts of biodegradable biobased polymers. Specifically, the techno-commercial analysis focuses on the commercial potential, financial assessment, and life-cycle assessment of these materials, as well as government initiatives to facilitate the transition towards biodegradable biobased polymers. Lastly, the environmental assessment focuses on the current challenges with biodegradation and methods of improving the recycling process and reusability of biodegradable biobased polymers.
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Affiliation(s)
- Swarn Jha
- J. Mike Walker ‘66 Department of Mechanical Engineering, Texas A&M University, College Station, TX 77843-3123, USA
| | - Bhargav Akula
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3123, USA
| | - Hannah Enyioma
- Department of Electrical Engineering, Texas A&M University, College Station, TX 77843-3123, USA
| | - Megan Novak
- Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3123, USA
| | - Vansh Amin
- Department of Electrical Engineering, Texas A&M University, College Station, TX 77843-3123, USA
| | - Hong Liang
- J. Mike Walker ‘66 Department of Mechanical Engineering, Texas A&M University, College Station, TX 77843-3123, USA
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12
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Yang Y, Cui J, Kong Y, Hou Y, Zhang H, Ma C. The Role of Hydrogel Biomaterials in the Intervention of Wound Healing and Skin Regeneration via Exosomes: A Systematic Review and Meta-Analysis of Preclinical Animal Studies. Adv Wound Care (New Rochelle) 2024. [PMID: 38874272 DOI: 10.1089/wound.2024.0058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2024] Open
Abstract
Significance: The combination of hydrogel biomaterials with exosomes to facilitate wound healing and skin regeneration is a promising approach. Recent Advances: Recent preclinical animal studies have focused on investigating the efficacy of hydrogel-based delivery systems for exosomes in promoting wound healing and skin regeneration. Critical Issues: Despite encouraging results, critical issues remain unresolved, such as optimizing hydrogel properties to enhance the efficacy of combined therapy with exosomes for wound and bridging the translational gap between preclinical and clinical applications. Future Directions: Future research endeavors should concentrate on refining hydrogel design to enhance exosome delivery efficacy, conducting rigorous clinical trials to assess the safety and efficacy of exosome-loaded hydrogels in human wound healing and skin regeneration, and exploring innovative strategies to maximize therapeutic outcomes.
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Affiliation(s)
- Yujia Yang
- Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, China
- Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, China
| | - Jinlei Cui
- Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, China
| | - Yajie Kong
- Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, China
| | - Yu Hou
- Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, China
| | - Haixia Zhang
- Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, China
| | - Cuiqing Ma
- Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, China
- Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang, China
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13
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Yang Y, Chen H, Li Y, Liang J, Huang F, Wang L, Miao H, Nanda HS, Wu J, Peng X, Zhou Y. Hydrogel Loaded with Extracellular Vesicles: An Emerging Strategy for Wound Healing. Pharmaceuticals (Basel) 2024; 17:923. [PMID: 39065772 PMCID: PMC11280375 DOI: 10.3390/ph17070923] [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: 05/30/2024] [Revised: 07/02/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
An increasing number of novel biomaterials have been applied in wound healing therapy. Creating beneficial environments and containing various bioactive molecules, hydrogel- and extracellular vesicle (EV)-based therapies have respectively emerged as effective approaches for wound healing. Moreover, the synergistic combination of these two components demonstrates more favorable outcomes in both chronic and acute wound healing. This review provides a comprehensive discussion and summary of the combined application of EVs and hydrogels to address the intricate scenario of wounds. The wound healing process and related biological mechanisms are outlined in the first section. Subsequently, the utilization of EV-loaded hydrogels during the wound healing process is evaluated and discussed. The moist environment created by hydrogels is conducive to wound tissue regeneration. Additionally, the continuous and controlled release of EVs from various origins could be achieved by hydrogel encapsulation. Finally, recent in vitro and in vivo studies reported on hydrogel dressings loaded with EVs are summarized and challenges and opportunities for the future clinical application of this therapeutic approach are outlined.
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Affiliation(s)
- Yucan Yang
- Key Laboratory of Liver Injury Diagnosis and Repair, and Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; (Y.Y.); (H.C.); (Y.L.); (J.L.); (F.H.); (L.W.); (H.M.)
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, Dongguan Key Laboratory of Advanced Drug Delivery and Biosensing Research and Development, School of Pharmacy, and Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China
| | - Huizhi Chen
- Key Laboratory of Liver Injury Diagnosis and Repair, and Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; (Y.Y.); (H.C.); (Y.L.); (J.L.); (F.H.); (L.W.); (H.M.)
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, Dongguan Key Laboratory of Advanced Drug Delivery and Biosensing Research and Development, School of Pharmacy, and Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China
| | - Yunjie Li
- Key Laboratory of Liver Injury Diagnosis and Repair, and Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; (Y.Y.); (H.C.); (Y.L.); (J.L.); (F.H.); (L.W.); (H.M.)
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, Dongguan Key Laboratory of Advanced Drug Delivery and Biosensing Research and Development, School of Pharmacy, and Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China
| | - Junting Liang
- Key Laboratory of Liver Injury Diagnosis and Repair, and Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; (Y.Y.); (H.C.); (Y.L.); (J.L.); (F.H.); (L.W.); (H.M.)
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, Dongguan Key Laboratory of Advanced Drug Delivery and Biosensing Research and Development, School of Pharmacy, and Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China
| | - Feng Huang
- Key Laboratory of Liver Injury Diagnosis and Repair, and Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; (Y.Y.); (H.C.); (Y.L.); (J.L.); (F.H.); (L.W.); (H.M.)
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, Dongguan Key Laboratory of Advanced Drug Delivery and Biosensing Research and Development, School of Pharmacy, and Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China
| | - Liyan Wang
- Key Laboratory of Liver Injury Diagnosis and Repair, and Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; (Y.Y.); (H.C.); (Y.L.); (J.L.); (F.H.); (L.W.); (H.M.)
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, Dongguan Key Laboratory of Advanced Drug Delivery and Biosensing Research and Development, School of Pharmacy, and Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China
| | - Huilai Miao
- Key Laboratory of Liver Injury Diagnosis and Repair, and Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; (Y.Y.); (H.C.); (Y.L.); (J.L.); (F.H.); (L.W.); (H.M.)
| | - Himansu Sekhar Nanda
- Biomaterials and Biomanufacturing Laboratory, Discipline of Mechanical Engineering, PDPM Indian Institute of Information Technology Design and Manufacturing, Jabalpur 482005, Madhya Pradesh, India;
| | - Jin Wu
- State Key Laboratory of Optoelectronic Materials and Technologies and the Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-sen University, Guangzhou 510275, China;
| | - Xinsheng Peng
- Key Laboratory of Liver Injury Diagnosis and Repair, and Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; (Y.Y.); (H.C.); (Y.L.); (J.L.); (F.H.); (L.W.); (H.M.)
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, Dongguan Key Laboratory of Advanced Drug Delivery and Biosensing Research and Development, School of Pharmacy, and Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China
| | - Yubin Zhou
- Key Laboratory of Liver Injury Diagnosis and Repair, and Department of Hepatobiliary Surgery, The 2nd Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; (Y.Y.); (H.C.); (Y.L.); (J.L.); (F.H.); (L.W.); (H.M.)
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, Dongguan Key Laboratory of Advanced Drug Delivery and Biosensing Research and Development, School of Pharmacy, and Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China
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He L, Zhang H, Zhao N, Liao L. A novel approach in biomedical engineering: The use of polyvinyl alcohol hydrogel encapsulating human umbilical cord mesenchymal stem cell-derived exosomes for enhanced osteogenic differentiation and angiogenesis in bone regeneration. Int J Biol Macromol 2024; 270:132116. [PMID: 38723803 DOI: 10.1016/j.ijbiomac.2024.132116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 04/09/2024] [Accepted: 05/04/2024] [Indexed: 05/19/2024]
Abstract
Developing effective methods for alveolar bone defect regeneration is a significant challenge in orthopedics. Exosomes from human umbilical cord mesenchymal stem cells (HUMSC-Exos) have shown potential in bone repair but face limitations due to undefined application methods and mechanisms. To address this, HUMSC-Exos were encapsulated in polyvinyl alcohol (PVA) hydrogel (Exo@PVA) to create a novel material for alveolar bone repair. This combination enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) more effectively than Exos alone. Additionally, Exo@PVA significantly improved alveolar bone regeneration and defect repair in rats. The microRNA-21-5p (miR-21-5p) in Exo@PVA, identified through the GEO database and analyzed via in silico methods, played a crucial role. miR-21-5p promoted BMSC osteogenic differentiation by inhibiting WWP1-mediated KLF5 ubiquitination and enhanced HUVEC angiogenesis by targeting ATP2B4. These findings underscore the potential of an Exo-based approach with PVA hydrogel scaffolds for bone defect repair, operating through the miR-21-5p/WWP1/ATP2B4 signaling axis.
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Affiliation(s)
- Longlong He
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China; Department of Implant Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China
| | - Hengwei Zhang
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China
| | - Ningbo Zhao
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China; Department of Implant Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China
| | - Lifan Liao
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China; Department of Implant Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China.
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15
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Bicer M. Revolutionizing dermatology: harnessing mesenchymal stem/stromal cells and exosomes in 3D platform for skin regeneration. Arch Dermatol Res 2024; 316:242. [PMID: 38795200 PMCID: PMC11127839 DOI: 10.1007/s00403-024-03055-4] [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: 11/28/2023] [Revised: 01/09/2024] [Accepted: 04/26/2024] [Indexed: 05/27/2024]
Abstract
Contemporary trends reveal an escalating interest in regenerative medicine-based interventions for addressing refractory skin defects. Conventional wound healing treatments, characterized by high costs and limited efficacy, necessitate a more efficient therapeutic paradigm to alleviate the economic and psychological burdens associated with chronic wounds. Mesenchymal stem/stromal cells (MSCs) constitute cell-based therapies, whereas cell-free approaches predominantly involve the utilization of MSC-derived extracellular vesicles or exosomes, both purportedly safe and effective. Exploiting the impact of MSCs by paracrine signaling, exosomes have emerged as a novel avenue capable of positively impacting wound healing and skin regeneration. MSC-exosomes confer several advantages, including the facilitation of angiogenesis, augmentation of cell proliferation, elevation of collagen production, and enhancement of tissue regenerative capacity. Despite these merits, challenges persist in clinical applications due to issues such as poor targeting and facile removal of MSC-derived exosomes from skin wounds. Addressing these concerns, a three-dimensional (3D) platform has been implemented to emend exosomes, allowing for elevated levels, and constructing more stable granules possessing distinct therapeutic capabilities. Incorporating biomaterials to encapsulate MSC-exosomes emerges as a favorable approach, concentrating doses, achieving intended therapeutic effectiveness, and ensuring continual release. While the therapeutic potential of MSC-exosomes in skin repair is broadly recognized, their application with 3D biomaterial scenarios remains underexplored. This review synthesizes the therapeutic purposes of MSCs and exosomes in 3D for the skin restoration, underscoring their promising role in diverse dermatological conditions. Further research may establish MSCs and their exosomes in 3D as a viable therapeutic option for various skin conditions.
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Affiliation(s)
- Mesude Bicer
- Department of Bioengineering, Faculty of Life and Natural Sciences, Abdullah Gul University, Kayseri, 38080, Turkey.
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16
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Martorana A, Lenzuni M, Contardi M, Palumbo FS, Cataldo S, Pettignano A, Catania V, Schillaci D, Summa M, Athanassiou A, Fiorica C, Bertorelli R, Pitarresi G. Schiff Base-Based Hydrogel Embedded with In Situ Generated Silver Nanoparticles Capped by a Hyaluronic Acid-Diethylenetriamine Derivative for Wound Healing Application. ACS APPLIED MATERIALS & INTERFACES 2024. [PMID: 38603548 DOI: 10.1021/acsami.4c00657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/13/2024]
Abstract
In this study, hydrogels were produced using a Schiff base reaction between two hyaluronic acid derivatives: one containing aldehyde groups (HA-Ald) and the other holding a diethylenetriamine with terminal amino groups (HA-DETA). The DETA portion promotes the in situ growth, complexation, and stabilization of silver nanoparticles (AgNPs), eliminating the need for external reducing agents. The reaction between HA-DETA and HA-Ald leads to the formation of imine bonds, which results in dynamically pH-responsive cross-linking. While the DETA capping ability helped in embedding the AgNPs, the on/off pH environmental responsivity of the hydrogel allows for a controlled and on-demand release of the drug, mainly when bacterial infections cause pH variation of the wound bed. The injectable hydrogels resulted in being highly compatible in contact with blood red cells, fibroblasts, and keratinocytes and capable of having a proliferative effect on an in vitro wound scratch model. The pH-responsive hydrogels showed proper antibacterial activity againstPseudomonas aeruginosaandStaphylococcus aureus, common bacterial strains presented in wound infections. Finally, in vivo wound model studies demonstrated an overall speeding up in the wound healing rate and advanced wound conditions in the experimental group treated with the hydrogels compared to control samples.
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Affiliation(s)
- Annalisa Martorana
- Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy
| | - Martina Lenzuni
- Smart Materials, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
| | - Marco Contardi
- Smart Materials, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
- Department of Earth and Environmental Sciences (DISAT), University of Milan-Bicocca, Piazza della Scienza, 20126 Milan, Italy
| | - Fabio S Palumbo
- Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy
| | - Salvatore Cataldo
- Department of Physics and Chemistry - Emilio Segrè, University of Palermo, Viale delle scienze, Ed. 17, 90128 Palermo, Italy
| | - Alberto Pettignano
- Department of Physics and Chemistry - Emilio Segrè, University of Palermo, Viale delle scienze, Ed. 17, 90128 Palermo, Italy
| | - Valentina Catania
- Department of Earth and Marine Sciences (DiSTeM), University of Palermo, Viale delle Scienze Ed. 16, 90128 Palermo, Italy
| | - Domenico Schillaci
- Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy
| | - Maria Summa
- Translational Pharmacology, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
| | | | - Calogero Fiorica
- Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy
| | - Rosalia Bertorelli
- Translational Pharmacology, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
| | - Giovanna Pitarresi
- Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy
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17
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Zhai Z, Edgar KJ. Polysaccharide Aldehydes and Ketones: Synthesis and Reactivity. Biomacromolecules 2024; 25:2261-2276. [PMID: 38490188 PMCID: PMC11005020 DOI: 10.1021/acs.biomac.4c00020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 03/02/2024] [Accepted: 03/04/2024] [Indexed: 03/17/2024]
Abstract
Polysaccharides are biodegradable, abundant, sustainable, and often benign natural polymers. The achievement of selective modification of polysaccharides is important for targeting specific properties and structures and will benefit future development of highly functional, sustainable materials. The synthesis of polysaccharides containing aldehyde or ketone moieties is a promising tool for achieving this goal because of the rich chemistry of aldehyde or ketone groups, including Schiff base formation, nucleophilic addition, and reductive amination. The obtained polysaccharide aldehydes or ketones themselves have rich potential for making useful materials, such as self-healing hydrogels, polysaccharide-protein therapeutic conjugates, or drug delivery vehicles. Herein, we review recent advances in synthesizing polysaccharides containing aldehyde or ketone moieties and briefly introduce their reactivity and corresponding applications.
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Affiliation(s)
- Zhenghao Zhai
- Macromolecules
Innovation Institute, Virginia Tech, Blacksburg, Virginia 24061, United States
| | - Kevin J. Edgar
- Macromolecules
Innovation Institute, Virginia Tech, Blacksburg, Virginia 24061, United States
- Department
of Sustainable Biomaterials, Virginia Tech, Blacksburg, Virginia 24061, United States
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18
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Omidian H, Wilson RL, Gill EJ. Advancements and Challenges in Self-Healing Hydrogels for Wound Care. Gels 2024; 10:241. [PMID: 38667660 PMCID: PMC11048759 DOI: 10.3390/gels10040241] [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: 02/25/2024] [Revised: 03/25/2024] [Accepted: 03/27/2024] [Indexed: 04/28/2024] Open
Abstract
This manuscript explores self-healing hydrogels as innovative solutions for diverse wound management challenges. Addressing antibiotic resistance and tailored wound care, these hydrogels exhibit promising outcomes, including accelerated wound closure and tissue regeneration. Advancements in multifunctional hydrogels with controlled drug release, antimicrobial properties, and real-time wound assessment capabilities signal a significant leap toward patient-centered treatments. However, challenges such as scalability, long-term safety evaluation, and variability in clinical outcomes persist. Future directions emphasize personalized medicine, manufacturing innovation, rigorous evaluation through clinical trials, and interdisciplinary collaboration. This manuscript features the ongoing pursuit of effective, adaptable, and comprehensive wound care solutions to transform medical treatments and improve patient outcomes.
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Affiliation(s)
- Hossein Omidian
- Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; (R.L.W.); (E.J.G.)
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19
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Zheng Y, Pan C, Xu P, Liu K. Hydrogel-mediated extracellular vesicles for enhanced wound healing: the latest progress, and their prospects for 3D bioprinting. J Nanobiotechnology 2024; 22:57. [PMID: 38341585 PMCID: PMC10858484 DOI: 10.1186/s12951-024-02315-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 01/26/2024] [Indexed: 02/12/2024] Open
Abstract
Extracellular vesicles have shown promising tissue recovery-promoting effects, making them increasingly sought-after for their therapeutic potential in wound treatment. However, traditional extracellular vesicle applications suffer from limitations such as rapid degradation and short maintenance during wound administration. To address these challenges, a growing body of research highlights the role of hydrogels as effective carriers for sustained extracellular vesicle release, thereby facilitating wound healing. The combination of extracellular vesicles with hydrogels and the development of 3D bioprinting create composite hydrogel systems boasting excellent mechanical properties and biological activity, presenting a novel approach to wound healing and skin dressing. This comprehensive review explores the remarkable mechanical properties of hydrogels, specifically suited for loading extracellular vesicles. We delve into the diverse sources of extracellular vesicles and hydrogels, analyzing their integration within composite hydrogel formulations for wound treatment. Different composite methods as well as 3D bioprinting, adapted to varying conditions and construction strategies, are examined for their roles in promoting wound healing. The results highlight the potential of extracellular vesicle-laden hydrogels as advanced therapeutic tools in the field of wound treatment, offering both mechanical support and bioactive functions. By providing an in-depth examination of the various roles that these composite hydrogels can play in wound healing, this review sheds light on the promising directions for further research and development. Finally, we address the challenges associated with the application of composite hydrogels, along with emerging trends of 3D bioprinting in this domain. The discussion covers issues such as scalability, regulatory considerations, and the translation of this technology into practical clinical settings. In conclusion, this review underlines the significant contributions of hydrogel-mediated extracellular vesicle therapy to the field of 3D bioprinting and wound healing and tissue regeneration. It serves as a valuable resource for researchers and practitioners alike, fostering a deeper understanding of the potential benefits, applications, and challenges involved in utilizing composite hydrogels for wound treatment.
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Affiliation(s)
- Yi Zheng
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, China
| | - Chuqiao Pan
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, China
| | - Peng Xu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, China.
| | - Kai Liu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, China.
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20
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Verling SD, Mashoudy K, Gompels M, Goldenberg G. Regenerative Medicine in Clinical and Aesthetic Dermatology. A COMPREHENSIVE GUIDE TO MALE AESTHETIC AND RECONSTRUCTIVE PLASTIC SURGERY 2024:65-79. [DOI: 10.1007/978-3-031-48503-9_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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21
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Yang P, Li Z, Fang B, Liu L. Self-healing hydrogels based on biological macromolecules in wound healing: A review. Int J Biol Macromol 2023; 253:127612. [PMID: 37871725 DOI: 10.1016/j.ijbiomac.2023.127612] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 10/02/2023] [Accepted: 10/20/2023] [Indexed: 10/25/2023]
Abstract
The complete healing of skin wounds has been a challenge in clinical treatment. Self-healing hydrogels are special hydrogels formed by distinctive physicochemically reversible bonds, and they are considered promising biomaterials in the biomedical field owing to their inherently good drug-carrying capacity as well as self-healing and repair abilities. Moreover, natural polymeric materials have received considerable attention in skin tissue engineering owing to their low cytotoxicity, low immunogenicity, and excellent biodegradation rates. In this paper, we review recent advances in the design of self-healing hydrogels based on natural polymers for skin-wound healing applications. First, we outline a variety of natural polymers that can be used to construct self-healing hydrogel systems and highlight the advantages and disadvantages of different natural polymers. We then describe the principle of self-healing hydrogels in terms of two different crosslinking mechanisms-physical and chemical-and dissect their performance characteristics based on the practical needs of skin-trauma applications. Next, we outline the biological mechanisms involved in the healing of skin wounds and describe the current application strategies for self-healing hydrogels based on these mechanisms. Finally, we analyze and summarize the challenges and prospects of natural-material-based self-healing hydrogels for skin applications.
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Affiliation(s)
- Pu Yang
- Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Zhen Li
- Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Bairong Fang
- Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
| | - Liangle Liu
- The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China.
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22
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Guo P, Wang Q, Chen L, Dingya K, Wang B. Ultrasound-Responsive Micelle-Encapsulated Mesenchymal Stem Cell-Derived EVs for the Treatment of Lower Limb Microcirculation Disease. ACS OMEGA 2023; 8:49406-49419. [PMID: 38162755 PMCID: PMC10753545 DOI: 10.1021/acsomega.3c08133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/25/2023] [Accepted: 11/27/2023] [Indexed: 01/03/2024]
Abstract
Lower limb microcirculatory ischemic disease is a vascular disorder primarily characterized by limb pain, gangrene, and potential amputation. It can be caused by various factors, such as hyperglycemia, atherosclerosis, and infection. Due to the extremely narrow luminal diameter in lower limb microcirculatory ischemic lesions, both surgical and medical interventions face challenges in achieving satisfactory therapeutic outcomes within the microvessels. Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) exhibit promising potential in the treatment of microcirculation ischemic lesions due to their small size and ability to promote angiogenesis. After undergoing substantial losses during the process of EVs transportation, only a minimal fraction of EVs can effectively reach the site of microcirculatory lesions, thereby compromising the therapeutic efficacy for microcirculatory disorders. Herein, an ultrasound-responsive system utilizing 2-(dimethylamino)ethyl methacrylate-b-2-tetrahydropyranyl methacrylate (DMAEMA-b-THPMA) micelles to encapsulate MSCs-EVs has been successfully constructed, with the aim of achieving localized and targeted release of EVs at the site of microcirculatory lesions. The reversible addition-fragmentation chain transfer (RAFT) polymerization method facilitates the successful synthesis of diblock copolymers comprising monomer 2-(dimethylamino)ethyl methacrylate (DMAEMA) and monomer 2-tetrahydropyranyl methacrylate (THPMA). The DMAEMA-b-THPMA micelles exhibit a nanoscale structure, reliable biocompatibility, ultrasound responsiveness, and conspicuous protection of EVs. Furthermore, the implementation of low-energy-density ultrasound can enhance angiogenesis by upregulating the levels of the vascular endothelial growth factor (VEGF). In in vivo experiments, the ultrasound-responsive system of the DMAEMA-b-THPMA micelles and MSCs-EVs synergistically enhances therapeutic efficacy by promoting angiogenesis, improving vascular permeability, and optimizing vascular. In conclusion, this work demonstrates bioapplication of an ultrasound-responsive micellar nanosystem loaded with EVs for the treatment of lower limb microcirculatory ischemic disorders.
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Affiliation(s)
- Peng Guo
- The
Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Qian Wang
- College
of Materials and Chemical Engineering, West
Anhui University, Luan 237012, Anhui, China
| | - Ling Chen
- The
First Affiliated Hospital of Lanzhou University, Lanzhou 730000, Gansu, China
| | - Kun Dingya
- The
Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, Henan, China
| | - Bing Wang
- The
Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, Henan, China
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23
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Simon L, Lapinte V, Morille M. Exploring the role of polymers to overcome ongoing challenges in the field of extracellular vesicles. J Extracell Vesicles 2023; 12:e12386. [PMID: 38050832 PMCID: PMC10696644 DOI: 10.1002/jev2.12386] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 11/03/2023] [Accepted: 11/09/2023] [Indexed: 12/07/2023] Open
Abstract
Extracellular vesicles (EVs) are naturally occurring nanoparticles released from all eucaryotic and procaryotic cells. While their role was formerly largely underestimated, EVs are now clearly established as key mediators of intercellular communication. Therefore, these vesicles constitute an attractive topic of study for both basic and applied research with great potential, for example, as a new class of biomarkers, as cell-free therapeutics or as drug delivery systems. However, the complexity and biological origin of EVs sometimes complicate their identification and therapeutic use. Thus, this rapidly expanding research field requires new methods and tools for the production, enrichment, detection, and therapeutic application of EVs. In this review, we have sought to explain how polymer materials actively contributed to overcome some of the limitations associated to EVs. Indeed, thanks to their infinite diversity of composition and properties, polymers can act through a variety of strategies and at different stages of EVs development. Overall, we would like to emphasize the importance of multidisciplinary research involving polymers to address persistent limitations in the field of EVs.
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Affiliation(s)
| | | | - Marie Morille
- ICGM, Univ Montpellier, CNRS, ENSCMMontpellierFrance
- Institut universitaire de France (IUF)ParisFrance
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24
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Zhang X, Ding P, Chen Y, Lin Z, Zhao X, Xie H. Human umbilical cord mesenchymal stem cell-derived exosomes combined with gelatin methacryloyl hydrogel to promote fractional laser injury wound healing. Int Wound J 2023; 20:4040-4049. [PMID: 37429607 PMCID: PMC10681517 DOI: 10.1111/iwj.14295] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/08/2023] [Accepted: 06/16/2023] [Indexed: 07/12/2023] Open
Abstract
To investigate whether human umbilical cord mesenchymal stem cell-derived exosomes combined with gelatin methacryloyl (GelMA) hydrogel are beneficial in promoting healing of laser-injured skin wounds in mice. Supernatants of cultured human umbilical cord mesenchymal stem cells (HUC-MSCs) were collected to obtain human umbilical cord MSC-derived exosomes (HUC-MSCs-Exos), which were combined with GelMA hydrogel complex to treat a mouse fractional laser injury model. The study was divided into PBS group, EX (HUC-MSCs-Exos) group, GEL (GelMA hydrogel) group and EX+GEL (HUC-MSCs-Exos combined with GelMA hydrogel) group. The healing of laser-injured skin in each group was observed by gross view and dermatoscopy, and changes in skin structure, angiogenesis and proliferation-related indexes were observed during the healing process of laser-injured skin in each group. The results of the animal experiments showed that the EX and GEL groups alone and the EL+EX group exhibited less inflammatory response compared to the PBS group. The EX and GEL groups showed marked tissue proliferation and favourable angiogenesis, which promoted the wound healing well. The GEL+EX group had the most significant promotion of wound healing compared to the PBS group. qPCR results showed that the expression levels of proliferation-related factors, including KI67 and VEGF and angiogenesis-related factor CD31, were significantly higher in the GEL+EX group than in the other groups, with a time-dependent effect. The combination of HUC-MSCs-Exos and GelMA hydrogel is beneficial in reducing the early inflammatory response of laser-injured skin in mice and promoting its proliferation and angiogenesis, which in turn promotes wound healing.
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Affiliation(s)
- Xinling Zhang
- Department of Plastic SurgeryPeking University Third HospitalBeijingChina
| | - Pengbing Ding
- Department of Plastic SurgeryPeking University Third HospitalBeijingChina
| | - Yujie Chen
- Department of Plastic SurgeryPeking University Third HospitalBeijingChina
| | - Zhiyu Lin
- Department of Plastic SurgeryPeking University Third HospitalBeijingChina
| | - Xun Zhao
- Department of Plastic SurgeryPeking University Third HospitalBeijingChina
| | - Hongbin Xie
- Department of Plastic SurgeryPeking University Third HospitalBeijingChina
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25
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Deng S, Cao H, Cui X, Fan Y, Wang Q, Zhang X. Optimization of exosome-based cell-free strategies to enhance endogenous cell functions in tissue regeneration. Acta Biomater 2023; 171:68-84. [PMID: 37730080 DOI: 10.1016/j.actbio.2023.09.023] [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: 06/27/2023] [Revised: 09/13/2023] [Accepted: 09/14/2023] [Indexed: 09/22/2023]
Abstract
Exosomes, nanoscale extracellular vesicles, play a crucial role in intercellular communication, owing to their biologically active cargoes such as RNAs and proteins. In recent years, they have emerged as a promising tool in the field of tissue regeneration, with the potential to initiate a new trend in cell-free therapy. However, it's worth noting that not all types of exosomes derived from cells are appropriate for tissue repair. Thus, selecting suitable cell sources is critical to ensure their efficacy in specific tissue regeneration processes. Current therapeutic applications of exosomes also encounter several limitations, including low-specific content for targeted diseases, non-tissue-specific targeting, and short retention time due to rapid clearance in vivo. Consequently, this review paper focuses on exosomes from diverse cell sources with functions specific to tissue regeneration. It also highlights the latest engineering strategies developed to overcome the functional limitations of natural exosomes. These strategies encompass the loading of specific therapeutic contents into exosomes, the endowment of tissue-specific targeting capability on the exosome surface, and the incorporation of biomaterials to extend the in vivo retention time of exosomes in a controlled-release manner. Collectively, these innovative approaches aim to synergistically enhance the therapeutic effects of natural exosomes, optimizing exosome-based cell-free strategies to boost endogenous cell functions in tissue regeneration. STATEMENT OF SIGNIFICANCE: Exosome-based cell-free therapy has recently emerged as a promising tool for tissue regeneration. This review highlights the characteristics and functions of exosomes from different sources that can facilitate tissue repair and their contributions to the regeneration process. To address the functional limitations of natural exosomes in therapeutic applications, this review provides an in-depth understanding of the latest engineering strategies. These strategies include optimizing exosomal contents, endowing tissue-specific targeting capability on the exosome surface, and incorporating biomaterials to extend the in vivo retention time of exosomes in a controlled-release manner. This review aims to explore and discuss innovative approaches that can synergistically improve endogenous cell functions in advanced exosome-based cell-free therapies for a broad range of tissue regeneration.
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Affiliation(s)
- Siyan Deng
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China; College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China
| | - Hongfu Cao
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China; College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China
| | - Xiaolin Cui
- School of medicine, the Chinese University of Hong Kong, Shenzhen, China; Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopedic Surgery & Musculoskeletal Medicine, Centre for Bioengineering & Nanomedicine, University of Otago, Christchurch, New Zealand
| | - Yujiang Fan
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China; College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
| | - Qiguang Wang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China; College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
| | - Xingdong Zhang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China; College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China
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26
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Tashak Golroudbari H, Banikarimi SP, Ayati A, Hadizadeh A, Khorasani Zavareh Z, Hajikhani K, Heirani-Tabasi A, Ahmadi Tafti M, Davoodi S, Ahmadi Tafti H. Advanced micro-/nanotechnologies for exosome encapsulation and targeting in regenerative medicine. Clin Exp Med 2023; 23:1845-1866. [PMID: 36705868 DOI: 10.1007/s10238-023-00993-7] [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: 11/26/2022] [Accepted: 01/05/2023] [Indexed: 01/28/2023]
Abstract
Exosomes, a subset of vesicles generated from cell membranes, are crucial for cellular communication. Exosomes' innate qualities have been used in recent studies to create nanocarriers for various purposes, including medication delivery and immunotherapy. As a result, a wide range of approaches has been designed to utilize their non-immunogenic nature, drug-loading capacity, or targeting ability. In this study, we aimed to review the novel methods and approaches in exosome engineering for encapsulation and targeting in regenerative medicine. We have assessed and evaluated each method's efficacy, advantages, and disadvantages and discussed the results of related studies. Even though the therapeutic role of non-allogenic exosomes has been demonstrated in several studies, their application has certain limitations as these particles are neither fully specific to target tissue nor tissue retainable. Hence, there is a strong demand for developing more efficient encapsulation methods along with more accurate and precise targeting methods, such as 3D printing and magnetic nanoparticle loading in exosomes, respectively.
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Affiliation(s)
- Hasti Tashak Golroudbari
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedeh Parnian Banikarimi
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Aryan Ayati
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Hadizadeh
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Khorasani Zavareh
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Kiana Hajikhani
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Asieh Heirani-Tabasi
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Ahmadi Tafti
- Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Davoodi
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Ahmadi Tafti
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
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27
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Cai F, Chen W, Zhao R, Liu Y. The capacity of exosomes derived from adipose-derived stem cells to enhance wound healing in diabetes. Front Pharmacol 2023; 14:1063458. [PMID: 37808198 PMCID: PMC10551633 DOI: 10.3389/fphar.2023.1063458] [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: 10/07/2022] [Accepted: 09/05/2023] [Indexed: 10/10/2023] Open
Abstract
The slow healing and nonhealing of diabetic wounds have long posed challenges for clinical practitioners. In the presence of elevated glucose levels, the body's regulatory mechanisms undergo alterations that impede normal wound healing processes, including cell proliferation, cytokine release, and growth factor activity. Consequently, the advancement of stem cell technology has sparked growing interest in utilizing stem cells and their derivatives as potential therapeutic agents to enhance diabetic wound healing. This paper aims to provide an academic review of the therapeutic effects of adipose-derived stem cell-EXOs (ADSC-EXOs) in diabetic wound healing. As a cell-free therapy, exosomes (EXOs) possess a multitude of proteins and growth factors that have been shown to be advantageous in promoting wound healing and mitigating the potential risks associated with stem cell therapy. By examining the current knowledge on ADSC-EXOs, this review seeks to offer insights and guidance for the potential application of EXOs in the treatment of diabetic wounds.
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Affiliation(s)
| | | | | | - Yi Liu
- Department of Burns and Plastic Surgery, and Wound Repair Surgery, The Lanzhou University Second Hospital, Lanzhou, Gansu, China
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28
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Pourtalebi Jahromi L, Rothammer M, Fuhrmann G. Polysaccharide hydrogel platforms as suitable carriers of liposomes and extracellular vesicles for dermal applications. Adv Drug Deliv Rev 2023; 200:115028. [PMID: 37517778 DOI: 10.1016/j.addr.2023.115028] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 06/26/2023] [Accepted: 07/27/2023] [Indexed: 08/01/2023]
Abstract
Lipid-based nanocarriers have been extensively investigated for their application in drug delivery. Particularly, liposomes are now clinically established for treating various diseases such as fungal infections. In contrast, extracellular vesicles (EVs) - small cell-derived nanoparticles involved in cellular communication - have just recently sparked interest as drug carriers but their development is still at the preclinical level. To drive this development further, the methods and technologies exploited in the context of liposome research should be applied in the domain of EVs to facilitate and accelerate their clinical translation. One of the crucial steps for EV-based therapeutics is designing them as proper dosage forms for specific applications. This review offers a comprehensive overview of state-of-the-art polysaccharide-based hydrogel platforms designed for artificial and natural vesicles with application in drug delivery to the skin. We discuss their various physicochemical and biological properties and try to create a sound basis for the optimization of EV-embedded hydrogels as versatile therapeutic avenues.
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Affiliation(s)
- Leila Pourtalebi Jahromi
- Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Biology, Pharmaceutical Biology, Staudtstr. 5, 91058 Erlangen, Germany
| | - Markus Rothammer
- Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Biology, Pharmaceutical Biology, Staudtstr. 5, 91058 Erlangen, Germany
| | - Gregor Fuhrmann
- Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Biology, Pharmaceutical Biology, Staudtstr. 5, 91058 Erlangen, Germany; FAU NeW, Nikolaus-Fiebiger-Str. 10, 91058 Erlangen, Germany.
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29
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Yang S, Chen S, Zhang C, Han J, Lin C, Zhao X, Guo H, Tan Y. Enhanced therapeutic effects of mesenchymal stem cell-derived extracellular vesicles within chitosan hydrogel in the treatment of diabetic foot ulcers. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2023; 34:43. [PMID: 37639051 PMCID: PMC10462522 DOI: 10.1007/s10856-023-06746-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 08/09/2023] [Indexed: 08/29/2023]
Abstract
Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising candidates for cell-free therapy in various diseases, including chronic cutaneous wounds. However, the lack of standardized protocols for EVs' preparation and identification poses a significant challenge to their clinical application. Thus, the objective was to develop a safe and efficient method for the large-scale production of hUCMSC-derived EVs while establishing a comprehensive identification protocol encompassing morphology, particle size distribution, protein expression, and purity. This study observed that most of the EVs acquired through the protocol exhibited either a cup-shaped or round-shaped structure, with a median diameter of ~73.25 nm. The proportions of EVs positive for CD9, CD63, and CD81 were 37.5%, 38.6%, and 19.8%, respectively. To enhance their therapeutic potential in wound treatment, EVs were incorporated into chitosan hydrogel, forming chitosan hydrogel-EVs (CS-EVs). Furthermore, it was demonstrated that CS-EVs exhibited continuous release of EVs into the surrounding environment and, importantly, that the released EVs were internalized by human umbilical vein endothelial cells (HUVECs), resulting in significant enhancement of cell migration and angiogenesis. Additionally, in a rat model of diabetic foot ulcers, CS-EVs demonstrated a robust therapeutic effect in promoting wound healing. Following a 15-day treatment period, the group treated with CS-EVs demonstrated an impressive 93.3% wound closure ability, accompanied by a high degree of re-epithelialization. In contrast, the control group exhibited only a 71.5% reduction in wound size. In summary, this study offers solutions for the purification, characterization, and application of EVs in clinical wound treatment. These results not only offer fresh perspectives on the involvement of hUCMSC-derived EVs in wound healing but also introduce a non-invasive approach for applying EVs that holds practical significance in skin repair.
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Affiliation(s)
- Shuangshuang Yang
- Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, Shandong, China
| | - Siyu Chen
- Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, Shandong, China
| | - Chengpeng Zhang
- Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, Shandong, China
| | - Jing Han
- Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, Shandong, China
| | - Chunyuan Lin
- Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, Shandong, China
| | - Xiaohui Zhao
- Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, Shandong, China
| | - Huizhen Guo
- Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, Shandong, China
| | - Yi Tan
- Qilu Cell Therapy Technology Co., Ltd, No.1758 Gangyuan Six Road, Ji'nan, Shandong, China.
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30
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Qin X, He J, Wang X, Wang J, Yang R, Chen X. The functions and clinical application potential of exosomes derived from mesenchymal stem cells on wound repair: a review of recent research advances. Front Immunol 2023; 14:1256687. [PMID: 37691943 PMCID: PMC10486026 DOI: 10.3389/fimmu.2023.1256687] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 08/07/2023] [Indexed: 09/12/2023] Open
Abstract
Wound repair is a complex problem for both clinical practitioners and scientific investigators. Conventional approaches to wound repair have been associated with several limitations, including prolonged treatment duration, high treatment expenses, and significant economic and psychological strain on patients. Consequently, there is a pressing demand for more efficacious and secure treatment modalities to enhance the existing treatment landscapes. In the field of wound repair, cell-free therapy, particularly the use of mesenchymal stem cell-derived exosomes (MSC-Exos), has made notable advancements in recent years. Exosomes, which are small lipid bilayer vesicles discharged by MSCs, harbor bioactive constituents such as proteins, lipids, microRNA (miRNA), and messenger RNA (mRNA). These constituents facilitate material transfer and information exchange between the cells, thereby regulating their biological functions. This article presents a comprehensive survey of the function and mechanisms of MSC-Exos in the context of wound healing, emphasizing their beneficial impact on each phase of the process, including the regulation of the immune response, inhibition of inflammation, promotion of angiogenesis, advancement of cell proliferation and migration, and reduction of scar formation.
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Affiliation(s)
- Xinchi Qin
- Zunyi Medical University, Zunyi, China
- Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan, China
| | - Jia He
- Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan, China
| | - Xiaoxiang Wang
- Department of Burn Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jingru Wang
- Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan, China
| | - Ronghua Yang
- Department of Burn and Plastic Surgery, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, China
| | - Xiaodong Chen
- Zunyi Medical University, Zunyi, China
- Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan, China
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31
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Alinezhad V, Esmaeilzadeh K, Bagheri H, Zeighami H, Kalantari-Hesari A, Jafari R, Makvandi P, Xu Y, Mohammadi H, Shahbazi MA, Maleki A. Engineering a platelet-rich plasma-based multifunctional injectable hydrogel with photothermal, antibacterial, and antioxidant properties for skin regeneration. Biomater Sci 2023; 11:5872-5892. [PMID: 37482933 DOI: 10.1039/d3bm00881a] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2023]
Abstract
Wound healing remains a significant challenge worldwide, necessitating the development of new wound dressings to aid in the healing process. This study presents a novel photothermally active hydrogel that contains platelet-rich plasma (PRP) for infected wound healing. The hydrogel was formed in a one pot synthesis approach by mixing alginate (Alg), gelatin (GT), polydopamine (PDA), and PRP, followed by the addition of CaCl2 as a cross-linker to prepare a multifunctional hydrogel (AGC-PRP-PDA). The hydrogel exhibited improved strength and good swelling properties. PDA nanoparticles (NPs) within the hydrogel endowed them with high photothermal properties and excellent antibacterial and antioxidant activities. Moreover, the hydrogels sustained the release of growth factors due to their ability to protect PRP. The hydrogels also exhibited good hemocompatibility and cytocompatibility, as well as high hemostatic properties. In animal experiments, the injectable hydrogels effectively filled irregular wounds and promoted infected wound healing by accelerating re-epithelialization, facilitating collagen deposition, and enhancing angiogenesis. The study also indicated that near-infrared light improved the healing process. Overall, these hydrogels with antibacterial, antioxidant, and hemostatic properties, as well as sustained growth factor release, show significant potential for skin regeneration in full-thickness, bacteria-infected wounds.
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Affiliation(s)
- Vajihe Alinezhad
- Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, 45139-56184 Zanjan, Iran.
| | - Kimia Esmaeilzadeh
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hadi Bagheri
- Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan 45139-56184, Iran
| | - Habib Zeighami
- Department of Microbiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan 45139-56184, Iran
| | - Ali Kalantari-Hesari
- Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamadan 6516738695, Iran
| | - Rahim Jafari
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Pooyan Makvandi
- School of Engineering, Institute for Bioengineering, The University of Edinburgh, Edinburgh, EH9 3JL, UK
| | - Yi Xu
- Department of Science & Technology, Department of Urology, Nano Medical Innovation & Collaboration Group (NMICG), The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
| | - Hamidreza Mohammadi
- Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran
- Department of Toxicology/Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohammad-Ali Shahbazi
- Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
- W.J. Kolff Institute for Biomedical Engineering and Materials Science, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
| | - Aziz Maleki
- Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, 45139-56184 Zanjan, Iran.
- Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan 45139-56184, Iran
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32
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Sousa P, Lopes B, Sousa AC, Moreira A, Coelho A, Alvites R, Alves N, Geuna S, Maurício AC. Advancements and Insights in Exosome-Based Therapies for Wound Healing: A Comprehensive Systematic Review (2018-June 2023). Biomedicines 2023; 11:2099. [PMID: 37626596 PMCID: PMC10452374 DOI: 10.3390/biomedicines11082099] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/14/2023] [Accepted: 07/22/2023] [Indexed: 08/27/2023] Open
Abstract
Exosomes have shown promising potential as a therapeutic approach for wound healing. Nevertheless, the translation from experimental studies to commercially available treatments is still lacking. To assess the current state of research in this field, a systematic review was performed involving studies conducted and published over the past five years. A PubMed search was performed for English-language, full-text available papers published from 2018 to June 2023, focusing on exosomes derived from mammalian sources and their application in wound healing, particularly those involving in vivo assays. Out of 531 results, 148 papers were selected for analysis. The findings revealed that exosome-based treatments improve wound healing by increasing angiogenesis, reepithelization, collagen deposition, and decreasing scar formation. Furthermore, there was significant variability in terms of cell sources and types, biomaterials, and administration routes under investigation, indicating the need for further research in this field. Additionally, a comparative examination encompassing diverse cellular origins, types, administration pathways, or biomaterials is imperative. Furthermore, the predominance of rodent-based animal models raises concerns, as there have been limited advancements towards more complex in vivo models and scale-up assays. These constraints underscore the substantial efforts that remain necessary before attaining commercially viable and extensively applicable therapeutic approaches using exosomes.
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Affiliation(s)
- Patrícia Sousa
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - Bruna Lopes
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - Ana Catarina Sousa
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - Alícia Moreira
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - André Coelho
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - Rui Alvites
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
- Instituto Universitário de Ciências da Saúde (CESPU), Avenida Central de Gandra 1317, 4585-116 Paredes, Portugal
| | - Nuno Alves
- Centre for Rapid and Sustainable Product Development, Polytechnic of Leiria, 2430-028 Marinha Grande, Portugal;
| | - Stefano Geuna
- Department of Clinical and Biological Sciences, Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Ospedale San Luigi, 10043 Turin, Italy;
| | - Ana Colette Maurício
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal; (P.S.); (B.L.); (A.C.S.); (A.M.); (A.C.); (R.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
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Tran HQ, Shahriar SS, Yan Z, Xie J. Recent Advances in Functional Wound Dressings. Adv Wound Care (New Rochelle) 2023; 12:399-427. [PMID: 36301918 PMCID: PMC10125407 DOI: 10.1089/wound.2022.0059] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 09/24/2022] [Indexed: 12/15/2022] Open
Abstract
Significance: Nowadays, the wound dressing is no longer limited to its primary wound protection ability. Hydrogel, sponge-like material, three dimensional-printed mesh, and nanofiber-based dressings with incorporation of functional components, such as nanomaterials, growth factors, enzymes, antimicrobial agents, and electronics, are able to not only prevent/treat infection but also accelerate the wound healing and monitor the wound-healing status. Recent Advances: The advances in nanotechnologies and materials science have paved the way to incorporate various functional components into the dressings, which can facilitate wound healing and monitor different biological parameters in the wound area. In this review, we mainly focus on the discussion of recently developed functional wound dressings. Critical Issues: Understanding the structure and composition of wound dressings is important to correlate their functions with the outcome of wound management. Future Directions: "All-in-one" dressings that integrate multiple functions (e.g., monitoring, antimicrobial, pain relief, immune modulation, and regeneration) could be effective for wound repair and regeneration.
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Affiliation(s)
- Huy Quang Tran
- Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - S.M. Shatil Shahriar
- Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Eppley Institute for Research in Cancer and Allied Diseases, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Zheng Yan
- Department of Mechanical & Aerospace Engineering, Biological & Chemical Engineering, University of Missouri, Columbia, Missouri, USA
- Department of Biomedical, Biological & Chemical Engineering, University of Missouri, Columbia, Missouri, USA
| | - Jingwei Xie
- Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Department of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
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34
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Garima, Sharma D, Kumar A, Mostafavi E. Extracellular vesicle-based biovectors in chronic wound healing: Biogenesis and delivery approaches. MOLECULAR THERAPY. NUCLEIC ACIDS 2023; 32:822-840. [PMID: 37273778 PMCID: PMC10238601 DOI: 10.1016/j.omtn.2023.05.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/29/2023]
Abstract
Chronic wounds remain an unresolved medical issue because of major social and therapeutic repercussions that require extensive focus. Recent related theragnostic focuses only on wound management and is not effectively promoting chronic wound healing. The rising number of patients with either under-healing or over-healing wounds highlights the ineffectiveness of current wound-healing treatments, and thus, there is an unmet need to focus on alternative treatments. To cover this gap, extracellular vesicles (EVs), for targeted delivery of therapeutics, are emerging as a potential therapy to treat both acute and persistent wounds. To address these issues, we explore the core biology of EVs, associated pharmacology, comprehension of immunogenic outcomes, and potential for long-term wound treatment with improved effectiveness and their nonacceptable side effects. Additionally, the therapeutic role of EVs in severe wound infections through biogenetic moderation, in combination with biomaterials (functional in nature), as well as drug carriers that can offer opportunities for the development of new treatments for this long-term condition, are also carefully elaborated, with an emphasis on biomaterial-based drug delivery systems. It is observed that exploring difficulties and potential outcomes of clinical translation of EV-based therapeutics for wound management has the potential to be adopted as a future therapy.
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Affiliation(s)
- Garima
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana 133207, India
| | - Deepika Sharma
- Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun, India
| | - Arun Kumar
- Department of Pharmacy, School of Health Sciences, Central University of South Bihar, Gaya 824209, India
| | - Ebrahim Mostafavi
- Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
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Dong J, Wu B, Tian W. Preparation of Apoptotic Extracellular Vesicles from Adipose Tissue and Their Efficacy in Promoting High-Quality Skin Wound Healing. Int J Nanomedicine 2023; 18:2923-2938. [PMID: 37288352 PMCID: PMC10243491 DOI: 10.2147/ijn.s411819] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 05/30/2023] [Indexed: 06/09/2023] Open
Abstract
Purpose A lot of strategies have been attempted to achieve high-quality skin wound healing, among them, fat transplantation has been used for skin wound repair and scar management and has shown beneficial effects. However, the underlying mechanism is still unclear. Recently, studies found that transplanted cells underwent apoptosis within a short period and apoptotic extracellular vesicles (ApoEVs) might play the therapeutic role. Methods In this study, we directly isolated apoptotic extracellular vesicles from adipose tissue (ApoEVs-AT) and evaluated their characteristics. In vivo, we investigated the therapeutic role of ApoEVs-AT in full-thickness skin wounds. The rate of wound healing, the quality of granulation tissue, and the area of scars were evaluated here. In vitro, we investigated the cellular behaviors of fibroblasts and endothelial cells induced by ApoEVs-AT, including cellular uptake, proliferation, migration, and differentiation. Results ApoEVs-AT could be successfully isolated from adipose tissue and possessed the basic characteristics of ApoEVs. In vivo, ApoEVs-AT could accelerate skin wound healing, improve the quality of granulation tissue, and reduce the area of scars. In vitro, ApoEVs-AT could be engulfed by fibroblasts and endothelial cells, significantly enhancing their proliferation and migration. Moreover, ApoEVs-AT could promote adipogenic differentiation and inhibit the fibrogenic differentiation of fibroblasts. Conclusion These findings indicated that ApoEVs could be successfully prepared from adipose tissue and showed the ability to promote high-quality skin wound healing by modulating fibroblasts and endothelial cells.
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Affiliation(s)
- Jia Dong
- Department of Stomatology, People’s Hospital of Longhua Shenzhen, Shenzhen, Guangdong, People’s Republic of China
| | - Bin Wu
- Department of Stomatology, People’s Hospital of Longhua Shenzhen, Shenzhen, Guangdong, People’s Republic of China
| | - Weidong Tian
- State Key Laboratory of Oral Disease, Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China
- National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China
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Zhang E, Phan P, Zhao Z. Cellular nanovesicles for therapeutic immunomodulation: A perspective on engineering strategies and new advances. Acta Pharm Sin B 2023; 13:1789-1827. [PMID: 37250173 PMCID: PMC10213819 DOI: 10.1016/j.apsb.2022.08.020] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 07/11/2022] [Accepted: 07/28/2022] [Indexed: 02/08/2023] Open
Abstract
Cellular nanovesicles which are referred to as cell-derived, nanosized lipid bilayer structures, have emerged as a promising platform for regulating immune responses. Owing to their outstanding advantages such as high biocompatibility, prominent structural stability, and high loading capacity, cellular nanovesicles are suitable for delivering various immunomodulatory molecules, such as small molecules, nucleic acids, peptides, and proteins. Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors, which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases. Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses, with the aim to explicate their applications for immunomodulation. We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities. We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.
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Affiliation(s)
- Endong Zhang
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA
| | - Philana Phan
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA
| | - Zongmin Zhao
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA
- Translational Oncology Program, University of Illinois Cancer Center, Chicago, IL 60612, USA
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Xu Y, Hu Q, Wei Z, Ou Y, Cao Y, Zhou H, Wang M, Yu K, Liang B. Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications. Biomater Res 2023; 27:36. [PMID: 37101201 PMCID: PMC10134570 DOI: 10.1186/s40824-023-00379-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 04/14/2023] [Indexed: 04/28/2023] Open
Abstract
Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements. Therefore, researchers have turned their attention to advanced polymer dressings and hydrogels to solve the therapeutic bottleneck of DU treatment. Hydrogels are a class of gels with a three-dimensional network structure that have good moisturizing properties and permeability and promote autolytic debridement and material exchange. Moreover, hydrogels mimic the natural environment of the extracellular matrix, providing suitable surroundings for cell proliferation. Thus, hydrogels with different mechanical strengths and biological properties have been extensively explored as DU dressing platforms. In this review, we define different types of hydrogels and elaborate the mechanisms by which they repair DUs. Moreover, we summarize the pathological process of DUs and review various additives used for their treatment. Finally, we examine the limitations and obstacles that exist in the development of the clinically relevant applications of these appealing technologies. This review defines different types of hydrogels and carefully elaborate the mechanisms by which they repair diabetic ulcers (DUs), summarizes the pathological process of DUs, and reviews various bioactivators used for their treatment.
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Affiliation(s)
- Yamei Xu
- Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
- Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
| | - Qiyuan Hu
- Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
- Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
| | - Zongyun Wei
- Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
- Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
| | - Yi Ou
- Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
- Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
| | - Youde Cao
- Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
- Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
- Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Distinct, Chongqing, 400042, P.R. China
| | - Hang Zhou
- Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
| | - Mengna Wang
- Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
- Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China
| | - Kexiao Yu
- Department of Orthopedics, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi Seventh Branch Road, Jiangbei District, Chongqing, 400021, P.R. China.
- Institute of Ultrasound Imaging of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China.
| | - Bing Liang
- Department of Pathology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China.
- Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing, 400016, P.R. China.
- Department of Pathology, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Distinct, Chongqing, 400042, P.R. China.
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Jiang H, Xu Q, Wang X, Shi L, Yang X, Sun J, Mei X. Preparation of Antibacterial, Arginine-Modified Ag Nanoclusters in the Hydrogel Used for Promoting Diabetic, Infected Wound Healing. ACS OMEGA 2023; 8:12653-12663. [PMID: 37065086 PMCID: PMC10099449 DOI: 10.1021/acsomega.2c07266] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 03/07/2023] [Indexed: 06/19/2023]
Abstract
Diabetic foot ulcers with complex healing wounds accompanied by bacterial infection are considered a significant clinical problem which are made worse by the lack of effective treatments. Traditional antibiotics and dressings have failed to address wound infection and healing, and multifunctional combination therapies are attractive for treating chronic wounds. In this study, arginine (Arg) was loaded onto the surface of silver nanoclusters and encapsulated in a hydrogel to achieve antibacterial, anti-inflammatory, angiogenic, and collagen deposition functions through the slow release of Arg combined with silver nanoclusters. In vitro studies indicated that Arg-Ag@H composites inhibited methicillin-resistant Staphylococcus aureus and Escherichia coli by 94 and 97%, respectively. The inhibition of bacterial biofilms reached 85%, and the migration ability of human venous endothelial cells (HUVECs) increased by 50%. In vitro studies showed that Arg-Ag@H composites increased the healing area of wounds by 26% and resulted in a 98% skin wound-healing rate. Safety studies confirmed the excellent biocompatibility of Arg-Ag@H. The results suggest that Arg-Ag@H offers new possibilities for treating chronic diabetic wounds.
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Affiliation(s)
- Housen Jiang
- Dalian
Medical University, Dalian 116044, Liaoning, China
- Department
of Hand and Foot Orthopedic Surgery, Weifang
People’s Hospital, Weifang 261042, Shandong, China
| | - Qin Xu
- Department
of Hand and Foot Orthopedic Surgery, Weifang
People’s Hospital, Weifang 261042, Shandong, China
| | - Xiaolin Wang
- Department
of Pathology, Weifang Hospital of Traditional
Chinese Medicine, Weifang 261042, Shandong, China
| | - Lin Shi
- Department
of Hand and Foot Orthopedic Surgery, Weifang
People’s Hospital, Weifang 261042, Shandong, China
| | - Xuedong Yang
- Department
of Hand and Foot Orthopedic Surgery, Weifang
People’s Hospital, Weifang 261042, Shandong, China
| | - Jianmin Sun
- Department
of Hand and Foot Orthopedic Surgery, Weifang
People’s Hospital, Weifang 261042, Shandong, China
| | - Xifan Mei
- Department
of Orthopedics, Third Affiliated Hospital
of Jinzhou Medical University, Jinzhou 121000, China
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Liang Y, Qiao L, Qiao B, Guo B. Conductive hydrogels for tissue repair. Chem Sci 2023; 14:3091-3116. [PMID: 36970088 PMCID: PMC10034154 DOI: 10.1039/d3sc00145h] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 02/20/2023] [Indexed: 02/23/2023] Open
Abstract
Conductive hydrogels (CHs) combine the biomimetic properties of hydrogels with the physiological and electrochemical properties of conductive materials, and have attracted extensive attention in the past few years. In addition, CHs have high conductivity and electrochemical redox properties and can be used to detect electrical signals generated in biological systems and conduct electrical stimulation to regulate the activities and functions of cells including cell migration, cell proliferation, and cell differentiation. These properties give CHs unique advantages in tissue repair. However, the current review of CHs is mostly focused on their applications as biosensors. Therefore, this article reviewed the new progress of CHs in tissue repair including nerve tissue regeneration, muscle tissue regeneration, skin tissue regeneration and bone tissue regeneration in the past five years. We first introduced the design and synthesis of different types of CHs such as carbon-based CHs, conductive polymer-based CHs, metal-based CHs, ionic CHs, and composite CHs, and the types and mechanisms of tissue repair promoted by CHs including anti-bacterial, antioxidant and anti-inflammatory properties, stimulus response and intelligent delivery, real-time monitoring, and promoted cell proliferation and tissue repair related pathway activation, which provides a useful reference for further preparation of bio-safer and more efficient CHs used in tissue regeneration.
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Affiliation(s)
- Yongping Liang
- State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University Xi'an 710049 China +86-29-83395131 +86-29-83395340
| | - Lipeng Qiao
- State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University Xi'an 710049 China +86-29-83395131 +86-29-83395340
| | - Bowen Qiao
- State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University Xi'an 710049 China +86-29-83395131 +86-29-83395340
| | - Baolin Guo
- State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University Xi'an 710049 China +86-29-83395131 +86-29-83395340
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University Xi'an 710049 China
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Joorabloo A, Liu T. Engineering exosome-based biomimetic nanovehicles for wound healing. J Control Release 2023; 356:463-480. [PMID: 36907562 DOI: 10.1016/j.jconrel.2023.03.013] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 03/05/2023] [Accepted: 03/07/2023] [Indexed: 03/14/2023]
Abstract
Complexity and difficulties in wound management are pressing concerns that affect patients' quality of life and may result in tissue infection, necrosis, and loss of local and systemic functions. Hence, novel approaches to accelerate wound healing are being actively explored over the last decade. Exosomes as important mediators of intercellular communications are promising natural nanocarriers due to their biocompatibility, low immunogenicity, drug loading and targeting capacities, and innate stability. More importantly, exosomes are developed as a versatile pharmaceutical engineering platform for wound repair. This review provides an overview of the biological and physiological functions of exosomes derived from a variety of biological origins during wound healing phases, strategies for exosomal engineering, and therapeutic applications in skin regeneration.
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Affiliation(s)
- Alireza Joorabloo
- NICM Health Research Institute, Western Sydney University, Westmead, Australia
| | - Tianqing Liu
- NICM Health Research Institute, Western Sydney University, Westmead, Australia.
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Du P, Diao L, Lu Y, Liu C, Li J, Chen Y, Chen J, Lv G, Chen X. Heparin-based sericin hydrogel-encapsulated basic fibroblast growth factor for in vitro and in vivo skin repair. Heliyon 2023; 9:e13554. [PMID: 36851964 PMCID: PMC9958445 DOI: 10.1016/j.heliyon.2023.e13554] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 02/03/2023] [Accepted: 02/03/2023] [Indexed: 02/11/2023] Open
Abstract
The treatment of full-thickness cutaneous wounds remains a significant challenge in clinical therapeutics. Exogenous growth factor (GF) has been applied in clinics to promote wound healing. However, the retention of GF on the wound bed after its direct application to the wound surface is difficult. Moreover, growth factors (GFs) are always inactivated in the complex wound healing microenvironment due to various factors, which significantly decrease the therapeutic effect. Sericin hydrogel (S) can be used as an effective carrier for GFs owing to its low immunogenicity, good biocompatibility, and good healing-promoting ability. Here, we designed a heparin-based sericin hydrogel (HS) -encapsulated basic fibroblast growth factor (bFGF-HS) to facilitate wound healing and skin regeneration. The hydrogel exhibited a three-dimensional (3D) microporous structure, excellent biodegradability, good adhesiveness, and low cytotoxicity. In vitro release of bFGF from bFGF-HS coacervates revealed that bFGF-HS might control the release of bFGF within 25 days through heparin regulation. bFGF-HS significantly promoted vascularization and re-epithelialization and improved collagen deposition, ultimately accelerating wound healing in vivo in mice. bFGF-HS treated wounds were also found to have more hair follicles and milder inflammatory reactions. Overall, this study provides a new therapeutic approach for full-thickness skin defect wounds using bFGF-HS.
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Affiliation(s)
- Pan Du
- Wuxi Medical School, Jiangnan University, Wuxi, 214122, China
| | - Ling Diao
- The Affifiliated Hospital of Jiangnan University, Jiangsu, 214000, China
| | - Yichi Lu
- Wuxi Medical School, Jiangnan University, Wuxi, 214122, China
| | - Chenyang Liu
- The Affifiliated Hospital of Jiangnan University, Jiangsu, 214000, China
| | - Jin Li
- Wuxi Medical School, Jiangnan University, Wuxi, 214122, China
| | - Yang Chen
- Nanjing University of Chinese Medicine, Nanjing, 210000, China
| | - Junfeng Chen
- Wuxi Medical School, Jiangnan University, Wuxi, 214122, China
| | - Guozhong Lv
- Wuxi Medical School, Jiangnan University, Wuxi, 214122, China
- The Affifiliated Hospital of Jiangnan University, Jiangsu, 214000, China
| | - Xue Chen
- Wuxi Medical School, Jiangnan University, Wuxi, 214122, China
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Amengual-Tugores AM, Ráez-Meseguer C, Forteza-Genestra MA, Monjo M, Ramis JM. Extracellular Vesicle-Based Hydrogels for Wound Healing Applications. Int J Mol Sci 2023; 24:ijms24044104. [PMID: 36835516 PMCID: PMC9967521 DOI: 10.3390/ijms24044104] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
Hydrogels and extracellular vesicle-based therapies have been proposed as emerging therapeutic assets in wound closure. The combination of these elements has given good results in managing chronic and acute wounds. The intrinsic characteristics of the hydrogels in which the extracellular vesicles (EVs) are loaded allow for overcoming barriers, such as the sustained and controlled release of EVs and the maintenance of the pH for their conservation. In addition, EVs can be obtained from different sources and through several isolation methods. However, some barriers must be overcome to transfer this type of therapy to the clinic, for example, the production of hydrogels containing functional EVs and identifying long-term storage conditions for EVs. The aim of this review is to describe the reported EV-based hydrogel combinations, along with the obtained results, and analyze future perspectives.
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Affiliation(s)
- Andreu Miquel Amengual-Tugores
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Carmen Ráez-Meseguer
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Maria Antònia Forteza-Genestra
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Marta Monjo
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
- Departament de Biologia Fonamental i Ciències de la Salut, University of the Balearic Islands (UIB), 07122 Palma, Spain
- Correspondence: (M.M.); (J.M.R.); Tel.: +34-971-25-96-07 (J.M.R.)
| | - Joana M. Ramis
- Cell Therapy and Tissue Engineering Group, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands (UIB), Ctra. Valldemossa km 7.5, 07122 Palma, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain
- Departament de Biologia Fonamental i Ciències de la Salut, University of the Balearic Islands (UIB), 07122 Palma, Spain
- Correspondence: (M.M.); (J.M.R.); Tel.: +34-971-25-96-07 (J.M.R.)
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Casajuana Ester M, Day RM. Production and Utility of Extracellular Vesicles with 3D Culture Methods. Pharmaceutics 2023; 15:pharmaceutics15020663. [PMID: 36839984 PMCID: PMC9961751 DOI: 10.3390/pharmaceutics15020663] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 02/13/2023] [Accepted: 02/13/2023] [Indexed: 02/18/2023] Open
Abstract
In recent years, extracellular vesicles (EVs) have emerged as promising biomarkers, cell-free therapeutic agents, and drug delivery carriers. Despite their great clinical potential, poor yield and unscalable production of EVs remain significant challenges. When using 3D culture methods, such as scaffolds and bioreactors, large numbers of cells can be expanded and the cell environment can be manipulated to control the cell phenotype. This has been employed to successfully increase the production of EVs as well as to enhance their therapeutic effects. The physiological relevance of 3D cultures, such as spheroids, has also provided a strategy for understanding the role of EVs in the pathogenesis of several diseases and to evaluate their role as tools to deliver drugs. Additionally, 3D culture methods can encapsulate EVs to achieve more sustained therapeutic effects as well as prevent premature clearance of EVs to enable more localised delivery and concentrated exosome dosage. This review highlights the opportunities and drawbacks of different 3D culture methods and their use in EV research.
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Liu JL, Kang DL, Mi P, Xu CZ, Zhu L, Wei BM. Mesenchymal Stem Cell Derived Extracellular Vesicles: Promising Nanomedicine for Cutaneous Wound Treatment. ACS Biomater Sci Eng 2023; 9:531-541. [PMID: 36607315 DOI: 10.1021/acsbiomaterials.2c00902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
A skin wound represents a rupture caused by external damage or the existence of underlying pathological conditions. Sometimes, skin wound healing processes may place a heavy burden on patients, families, and society. Wound healing processes mainly consist of several continuous, dynamic, but overlapping stages, namely, the coagulation stage, inflammation stage, proliferation stage, and remodeling stage. Bacterial infection, excessive inflammation, impaired angiogenesis, and scar formation constitute the four significant factors impeding the recovery efficacy of skin wounds. This encourages scientists to develop multifunctional nanomedicines to meet challenging needs. As we know, mesenchymal stem cells (MSCs) have been widely explored for wound repair owing to their unique capability for self-renewal and multipotency. However, problems including immune concerns and legal restrictions should be properly resolved before MSC-based therapeutics are safely and widely used in clinics. Besides, maintaining the high viability/proliferation capability of MSCs during administration processes and therapy procedures is also one of the biggest technical bottlenecks. Extracellular vesicles (EVs) are cell-derived nanovesicles, that not only possess the basic characteristics and functions of their corresponding maternal cells but also contain several outstanding advantages including abundant sources, excellent biocompatibility, and convenient administration routes. Furthermore, the membrane surface and cavity are easy to flexibly modify to meet versatile application needs. Recently, MSC-derived EVs have emerged as promising therapeutics for skin wound repair. However, current reviews are too broad and rarely focused on the specific roles of EVs in the different stages of wound recovery. Therefore, it is quite necessary to demonstrate the significance of stem cell-derived EVs in promoting wound healing from several specific aspects. Here, this review primarily tries to provide critical comments on current advances in EVs derived from MSCs for wound repair, particularly elaborating on their impressive roles in effectively eliminating infections, inhibiting inflammation, promoting angiogenesis, and reducing scar formation. Last but not least, current limitations and future prospects of EVs derived from MSCs in the areas of wound repair are also objectively analyzed.
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Affiliation(s)
- Jia-Lin Liu
- School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Changqing Garden, Wuhan, 430023 Hubei, China
| | - De-Lai Kang
- School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Changqing Garden, Wuhan, 430023 Hubei, China
| | - Peng Mi
- School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Changqing Garden, Wuhan, 430023 Hubei, China
| | - Cheng-Zhi Xu
- School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Changqing Garden, Wuhan, 430023 Hubei, China
| | - Lian Zhu
- School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Changqing Garden, Wuhan, 430023 Hubei, China
| | - Ben-Mei Wei
- School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Changqing Garden, Wuhan, 430023 Hubei, China
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Khazaei F, Rezakhani L, Alizadeh M, Mahdavian E, Khazaei M. Exosomes and exosome-loaded scaffolds: Characterization and application in modern regenerative medicine. Tissue Cell 2023; 80:102007. [PMID: 36577349 DOI: 10.1016/j.tice.2022.102007] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 12/20/2022] [Accepted: 12/21/2022] [Indexed: 12/24/2022]
Abstract
Exosomes (EXOs) are extracellular vesicles derived from the endosome. These heterogeneous nanoparticles (30-150 nm) are secreted from various cells and play important biological roles in intercellular communication. EXOs have received much attention for application in regenerative therapies and tissue repair due to their stability, biosafety, and functional versatility. However, in their free forms, "EXOs have poor bioavailability" at the site of action and are devoid of controlled-release mechanisms. These issues have been largely remedied by scaffolding EXOs with appropriate biomaterials such as hydrogels to create EXOs -loaded scaffold (ELS). These biomaterial-based scaffolds can be rationally designed and functionalized to enhance various aspects of ELS including bioavailability, biocompatibility, and loading/release control. Additionally, the ELS are superior to free EXOs due to reduced injection-related side effects. This review article provides a comprehensive and updated account of EXOs and ELS isolation, characterization, and application in regenerative medicine with a focus on soft tissue repair. We also offer insights into the advantages of ELS therapy compared to stem cell therapy towards application in wound healing, cardiac and bone repair. ELS promotes cell migration to the scaffold and will cause better homing of exosomes. Different types of scaffolds are made and each one can be modified based on the repair in the target tissues so that the reactions between the scaffold and exosome take place properly and effective signals are created for tissue repair.
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Affiliation(s)
- Fatemeh Khazaei
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, the Islamic Republic of Iran
| | - Leila Rezakhani
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, the Islamic Republic of Iran; Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, the Islamic Republic of Iran.
| | - Morteza Alizadeh
- Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, the Islamic Republic of Iran
| | - Elahe Mahdavian
- Louisiana State University in Shreveport, One University Place, Shreveport, LA 71115, USA
| | - Mozafar Khazaei
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, the Islamic Republic of Iran; Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, the Islamic Republic of Iran.
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Ju Y, Hu Y, Yang P, Xie X, Fang B. Extracellular vesicle-loaded hydrogels for tissue repair and regeneration. Mater Today Bio 2023; 18:100522. [PMID: 36593913 PMCID: PMC9803958 DOI: 10.1016/j.mtbio.2022.100522] [Citation(s) in RCA: 169] [Impact Index Per Article: 84.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 12/04/2022] [Accepted: 12/13/2022] [Indexed: 12/24/2022] Open
Abstract
Extracellular vesicles (EVs) are a collective term for nanoscale or microscale vesicles secreted by cells that play important biological roles. Mesenchymal stem cells are a class of cells with the potential for self-healing and multidirectional differentiation. In recent years, numerous studies have shown that EVs, especially those secreted by mesenchymal stem cells, can promote the repair and regeneration of various tissues and, thus, have significant potential in regenerative medicine. However, due to the rapid clearance capacity of the circulatory system, EVs are barely able to act persistently at specific sites for repair of target tissues. Hydrogels have good biocompatibility and loose and porous structural properties that allow them to serve as EV carriers, thereby prolonging the retention in certain specific areas and slowing the release of EVs. When EVs are needed to function at specific sites, the EV-loaded hydrogels can stand as an excellent approach. In this review, we first introduce the sources, roles, and extraction and characterization methods of EVs and describe their current application status. We then review the different types of hydrogels and discuss factors influencing their abilities to carry and release EVs. We summarize several strategies for loading EVs into hydrogels and characterizing EV-loaded hydrogels. Furthermore, we discuss application strategies for EV-loaded hydrogels and review their specific applications in tissue regeneration and repair. This article concludes with a summary of the current state of research on EV-loaded hydrogels and an outlook on future research directions, which we hope will provide promising ideas for researchers.
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Key Words
- 4-arm-PEG-MAL, four-armed polyethylene glycol (PEG) functionalized with maleimide group
- AD/CS/RSF, alginate-dopamine chondroitin sulfate and regenerated silk fibroin
- ADSC, Adipose derived mesenchymal stem cells
- ADSC-EVs, adipose mesenchymal stem cells derived EVs
- ADSC-Exos, adipose mesenchymal stem cells derived exosomes
- ATRP, Atom transfer radical polymerization
- BCA, bicinchoninic acid
- BMSC, Bone marrow mesenchymal stem cells
- BMSC-EVs, bone marrow mesenchymal stem cells derived EVs
- BMSC-Exos, bone marrow mesenchymal stem cells derived exosomes
- CGC, chitosan-gelatin-chondroitin sulfate
- CL, chitosan lactate
- CNS, central nervous system
- CPCs, cardiac progenitor cells
- CS-g-PEG, chitosan-g-PEG
- DPSC-Exos, dental pulp stem cells derived exosomes
- ECM, extracellular matrix
- EGF, epidermal growth factor
- EVMs, extracellular vesicles mimetics
- EVs, Extracellular vesicles
- Exos, Exosomes
- Exosome
- Extracellular vesicle
- FEEs, functionally engineered EVs
- FGF, fibroblast growth factor
- GelMA, Gelatin methacryloyl
- HA, Hyaluronic acid
- HAMA, Hyaluronic acid methacryloyl
- HG, nano-hydroxyapatite-gelatin
- HIF-1 α, hypoxia-inducible factor-1 α
- HS-HA, hypoxia-sensitive hyaluronic acid
- HUVEC, human umbilical vein endothelial cell
- Hydrogel
- LAP, Lithium Phenyl (2,4,6-trimethylbenzoyl) phosphinate
- LSCM, laser scanning confocal microscopy
- MC-CHO, Aldehyde methylcellulose
- MMP, matrix metalloproteinase
- MNs, microneedles
- MSC-EVs, mesenchymal stem cells derived EVs
- MSC-Exos, mesenchymal stem cells derived exosomes
- MSCs, mesenchymal stem cells
- NPCs, neural progenitor cells
- NTA, nanoparticle tracking analysis
- OHA, oxidized hyaluronic acid
- OSA, oxidized sodium alginate
- PDA, Polydopamine
- PDLLA, poly(D l-lactic acid)
- PDNPs-PELA, Polydopamine nanoparticles incorporated poly (ethylene glycol)-poly(ε-cap-rolactone-co-lactide)
- PEG, Polyethylene glycol
- PF-127, Pluronic F-127
- PHEMA, phenoxyethyl methacrylate
- PIC, photo-induced imine crosslinking
- PKA, protein kinase A system
- PLA, Poly lactic acid
- PLGA, polylactic acid-hydroxy acetic acid copolymer
- PLLA, poly(l-lactic acid)
- PPy, polypyrrole
- PVA, polyvinyl alcohol
- RDRP, Reversible deactivation radical polymerization
- Regeneration
- SCI, spinal cord injury
- SEM, Scanning electron microscopy
- SF, Silk fibroin
- SPT, single-particle tracking
- TEM, transmission electron microscopy
- Tissue repair
- UMSC, umbilical cord mesenchymal stem cells
- UMSC-EVs, umbilical cord mesenchymal stem cells derived EVs
- UMSC-Exos, umbilical cord mesenchymal stem cells derived exosomes
- UV, ultraviolet
- VEGF, vascular endothelial growth factor
- VEGF-R, vascular endothelial growth factor receptor
- WB, western blotting
- dECM, decellularized ECM
- hiPS-MSC-Exos, human induced pluripotent stem cell-MSC-derived exosomes
- iPS-CPCs, pluripotent stem cell-derived cardiac progenitors
- nHP, nanohydroxyapatite/poly-ε-caprolactone
- sEVs, small extracellular vesicles
- β-TCP, β-Tricalcium Phosphate
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Affiliation(s)
- Yikun Ju
- Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China
| | - Yue Hu
- School of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, People's Republic of China
| | - Pu Yang
- Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China
| | - Xiaoyan Xie
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China
| | - Bairong Fang
- Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, People's Republic of China
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Huang C, Yuan W, Chen J, Wu LP, You T. Construction of Smart Biomaterials for Promoting Diabetic Wound Healing. Molecules 2023; 28:molecules28031110. [PMID: 36770776 PMCID: PMC9920261 DOI: 10.3390/molecules28031110] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 01/24/2023] Open
Abstract
Diabetes mellitus is a complicated metabolic disease that has become one of the fastest-growing health crises in modern society. Diabetic patients may suffer from various complications, and diabetic foot is one of them. It can lead to increased rates of lower-extremity amputation and mortality, even seriously threatening the life and health of patients. Because its healing process is affected by various factors, its management and treatment are very challenging. To address these problems, smart biomaterials have been developed to expedite diabetic wound closure and improve treatment outcomes. This review begins with a discussion of the basic mechanisms of wound recovery and the limitations of current dressings used for diabetic wound healing. Then, the categories and characteristics of the smart biomaterial scaffolds, which can be utilized as a delivery system for drugs with anti-inflammatory activity, bioactive agency, and antibacterial nanoparticles for diabetic wound treatment were described. In addition, it can act as a responsive system to the stimulus of the pH, reactive oxygen species, and glucose concentration from the wound microenvironment. These results show that smart biomaterials have an enormous perspective for the treatment of diabetic wounds in all stages of healing. Finally, the advantages of the construction of smart biomaterials are summarized, and possible new strategies for the clinical management of diabetic wounds are proposed.
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Affiliation(s)
- Chan Huang
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Weiyan Yuan
- School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Jun Chen
- Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Lin-Ping Wu
- Center for Chemical Biology and Drug Discovery, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
- Correspondence: (L.-P.W.); (T.Y.)
| | - Tianhui You
- Center for Drug Research and Development, Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Correspondence: (L.-P.W.); (T.Y.)
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Liu WS, Liu Y, Gao J, Zheng H, Lu ZM, Li M. Biomembrane-Based Nanostructure- and Microstructure-Loaded Hydrogels for Promoting Chronic Wound Healing. Int J Nanomedicine 2023; 18:385-411. [PMID: 36703725 PMCID: PMC9871051 DOI: 10.2147/ijn.s387382] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 12/20/2022] [Indexed: 01/20/2023] Open
Abstract
Wound healing is a complex and dynamic process, and metabolic disturbances in the microenvironment of chronic wounds and the severe symptoms they cause remain major challenges to be addressed. The inherent properties of hydrogels make them promising wound dressings. In addition, biomembrane-based nanostructures and microstructures (such as liposomes, exosomes, membrane-coated nanostructures, bacteria and algae) have significant advantages in the promotion of wound healing, including special biological activities, flexible drug loading and targeting. Therefore, biomembrane-based nanostructure- and microstructure-loaded hydrogels can compensate for their respective disadvantages and combine the advantages of both to significantly promote chronic wound healing. In this review, we outline the loading strategies, mechanisms of action and applications of different types of biomembrane-based nanostructure- and microstructure-loaded hydrogels in chronic wound healing.
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Affiliation(s)
- Wen-Shang Liu
- Department of Dermatology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China
| | - Yu Liu
- Department of Gastroenterology, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China
| | - Jie Gao
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China
| | - Hao Zheng
- Department of General Surgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China
| | - Zheng-Mao Lu
- Department of General Surgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China,Zheng-Mao Lu, Department of General Surgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China, Tel +086-13651688596, Fax +086-021-31161589, Email
| | - Meng Li
- Department of Dermatology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China,Correspondence: Meng Li, Department of Dermatology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China, Tel +086-15000879978, Fax +086-021-23271699, Email
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Dong J, Wu B, Tian W. How to maximize the therapeutic effect of exosomes on skin wounds in diabetes mellitus: Review and discussion. Front Endocrinol (Lausanne) 2023; 14:1146991. [PMID: 37051206 PMCID: PMC10083381 DOI: 10.3389/fendo.2023.1146991] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 03/16/2023] [Indexed: 03/29/2023] Open
Abstract
Chronic skin wound healing, especially in diabetes mellitus, is still unsolved. Although many efforts have been made to treat diabetic skin wounds, current strategies have achieved limited effectiveness. Nowadays, a great number of studies have shown that exosomes might be a promising approach for treating diabetic wounds. Many studies and reviews have focused on investigating and discussing the effectiveness and mechanism of exosomes. However, maximizing its value in treating skin wounds in diabetes mellitus requires further consideration. In this review, we reviewed and discussed the aspects that could be further improved in this process, including finding a better source of exosomes, engineering exosomes, adjusting dosage and frequency, and combining more efficient delivery methods. This review provided an overview and idea of what we can do to improve the therapeutic effect of exosomes on skin wounds in diabetes mellitus. Only by combining all the factors that affect the effectiveness of exosomes in diabetic wound healing can we further promote their clinical usefulness.
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Affiliation(s)
- Jia Dong
- Department of Stomatology, People's Hospital of Longhua Shenzhen, Shenzhen, Guangdong, China
- State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China
- *Correspondence: Jia Dong, ; Weidong Tian,
| | - Bin Wu
- Department of Stomatology, People's Hospital of Longhua Shenzhen, Shenzhen, Guangdong, China
| | - Weidong Tian
- State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China
- *Correspondence: Jia Dong, ; Weidong Tian,
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50
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Zhao H, Li Z, Wang Y, Zhou K, Li H, Bi S, Wang Y, Wu W, Huang Y, Peng B, Tang J, Pan B, Wang B, Chen Z, Zhang Z. Bioengineered MSC-derived exosomes in skin wound repair and regeneration. Front Cell Dev Biol 2023; 11:1029671. [PMID: 36923255 PMCID: PMC10009159 DOI: 10.3389/fcell.2023.1029671] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 02/16/2023] [Indexed: 03/02/2023] Open
Abstract
Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed.
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Affiliation(s)
- Hanxing Zhao
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China.,Department of Plastic Reconstructive and Aesthetic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Zhengyong Li
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China.,Department of Plastic Reconstructive and Aesthetic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Yixi Wang
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Kai Zhou
- Department of Plastic Reconstructive and Aesthetic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Hairui Li
- Department of Plastic Reconstructive and Aesthetic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Siwei Bi
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yudong Wang
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Wenqing Wu
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yeqian Huang
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Peng
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China.,Department of Plastic Reconstructive and Aesthetic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Jun Tang
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China.,Department of Plastic Reconstructive and Aesthetic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Bo Pan
- Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Baoyun Wang
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China.,Department of Plastic Reconstructive and Aesthetic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Zhixing Chen
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China.,Department of Plastic Reconstructive and Aesthetic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
| | - Zhenyu Zhang
- Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu, China.,Department of Plastic Reconstructive and Aesthetic Surgery, West China Tianfu Hospital, Sichuan University, Chengdu, China
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