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Jiang K, Xu Y, Wang Y, Yin N, Huang F, Chen M. Deciphering the role of IL-17D, its newly identified receptor CD93, and IL-17D-CD93 axis in health and disease. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2025:vkaf061. [PMID: 40258301 DOI: 10.1093/jimmun/vkaf061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 02/23/2025] [Indexed: 04/23/2025]
Abstract
This review explores interleukin (IL)-17D and its receptor CD93, highlighting their structural, functional, and clinical aspects. Identifying CD93 as the receptor for IL-17D has advanced understanding of the IL-17 family and its signaling pathways. IL-17D, with its unique glycoprotein structure, plays diverse roles in oxidative stress response and potential antitumor therapies. It is involved in autoimmune diseases, infections, and cancers, making it a promising therapeutic target. CD93 is crucial in various biological processes, from angiogenesis to inflammatory diseases. CD93's implications in cancers, neuroinflammation, and metabolism highlight its significance as a potential prognostic marker and therapeutic target. The review emphasizes IL-17D and CD93 as promising areas for future research, offering insights into their signaling pathways and potential applications in personalized medicine. Deciphering the relationship between IL-17D and CD93 is in its infancy and invites exploration for transformative advancements in immunology and beyond.
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Affiliation(s)
- Kexin Jiang
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
- Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Yanjiani Xu
- Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
- Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Yan Wang
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
- Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Nanhao Yin
- Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Fangyang Huang
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
- Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Mao Chen
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
- Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
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Xu Y, Jia Y, Wu N, Wang J, He L, Yang D. CD93 Ameliorates Diabetic Wounds by Promoting Angiogenesis via the p38MAPK/MK2/HSP27 Axis. Eur J Vasc Endovasc Surg 2023; 66:707-721. [PMID: 37295599 DOI: 10.1016/j.ejvs.2023.06.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 04/04/2023] [Accepted: 06/01/2023] [Indexed: 06/12/2023]
Abstract
OBJECTIVE Diabetic wounds are a complication of diabetes mellitus, which is characterised by microcirculation dysfunction caused by decreased local blood supply and insufficient metabolic exchange. Clinically, in addition to glycaemic control, the most important treatment for diabetic wounds is to promote local angiogenesis, which accelerates wound healing. The authors previous study demonstrated that CD93, which is specifically expressed on vascular endothelial cells (ECs), redundantly regulates angiogenesis in zebrafish, suggesting that CD93 is a potential angiogenic molecule. However, the role of CD93 in diabetic wounds has not yet been elucidated. METHODS The angiogenic effects of CD93 were studied from four aspects: exogenous, endogenous, in vitro, and in vivo. CD93 recombinant protein was used in microvascular ECs and in mice to observe angiogenesis in vitro and in vivo. The wound model was established in CD93-/- and wild type diabetic mice, and the degree of wound healing as well as the amount and maturity of neovascularisation were investigated. The possible mechanism of CD93 in angiogenesis was determined by CD93 overexpression in cultured ECs. RESULTS CD93 recombinant protein was found to exogenously promote tube formation and sprouting of ECs. It also recruited cells to promote the formation of vascular like structures in subcutaneous tissue and accelerated wound healing by optimising angiogenesis and re-epithelisation. Furthermore, CD93 deficiency was observed to delay wound repair, characterised by reduced neovascularisation, vascular maturity, and re-epithelisation level. Mechanically, CD93 activated the p38MAPK/MK2/HSP27 signalling pathway, positively affecting the angiogenic functions of ECs. CONCLUSION This study demonstrated that CD93 promotes angiogenesis both in vitro and in vivo and that its angiogenic role in vitro is mediated by the p38MAPK/MK2/HSP27 signalling pathway. It was also found that CD93 exerts beneficial effects on wound healing in diabetic mice by promoting angiogenesis and re-epithelisation.
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Affiliation(s)
- Yuan Xu
- College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Yuhuan Jia
- College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Na Wu
- College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Jie Wang
- College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Liwen He
- College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Deqin Yang
- College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
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Cui Z, Xu Y, Wu P, Lu Y, Tao Y, Zhou C, Cui R, Li J, Han R. NAT10 promotes osteogenic differentiation of periodontal ligament stem cells by regulating VEGFA-mediated PI3K/AKT signaling pathway through ac4C modification. Odontology 2023; 111:870-882. [PMID: 36879181 DOI: 10.1007/s10266-023-00793-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 02/08/2023] [Indexed: 03/08/2023]
Abstract
Periodontal tissue regeneration engineering based on human periodontal ligament stem cells (hPDLSCs) provides a broad prospect for the treatment of periodontal disease. N-Acetyltransferase 10 (NAT10)-catalyzed non-histone acetylation is widely involved in physiological or pathophysiological processes. However, its function in hPDLSCs is still missing. hPDLSCs were isolated, purified, and cultured from extracted teeth. Surface markers were detected by flow cytometry. Osteogenic, adipogenic, and chondrogenic differentiation potential was detected by alizarin red staining (ARS), oil red O staining, and Alcian blue staining. Alkaline phosphatase (ALP) activity was assessed by ALP assay. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the expression of key molecules, such as NAT10, Vascular endothelial growth factor A (VEGFA), PI3K/AKT pathway, as well as bone markers (RUNX2, OCN, OPN). RNA-Binding Protein Immunoprecipitation PCR (RIP-PCR) was used to detect the N4-acetylcytidine (ac4C) mRNA level. Genes related to VEGFA were identified by bioinformatics analysis. NAT10 was highly expressed in the osteogenic differentiation process with enhanced ALP activity and osteogenic capability, and elevated expression of osteogenesis-related markers. The ac4C level and expression of VEGFA were obviously regulated by NAT10 and overexpression of VEGFA also had similar effects to NAT10. The phosphorylation level of PI3K and AKT was also elevated by overexpression of VEGFA. VEGFA could reverse the effects of NAT10 in hPDLSCs. NAT10 enhances the osteogenic development of hPDLSCs via regulation of the VEGFA-mediated PI3K/AKT signaling pathway by ac4C alteration.
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Affiliation(s)
- Zhao Cui
- Pediatric Surgery, Children's Hospital of Changchun, Changchun, 130021, Jilin Province, People's Republic of China
| | - Yunhe Xu
- Department of Stomatology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, People's Republic of China
| | - Peng Wu
- Pediatric Surgery, Children's Hospital of Changchun, Changchun, 130021, Jilin Province, People's Republic of China
| | - Ying Lu
- Pediatric Surgery, Children's Hospital of Changchun, Changchun, 130021, Jilin Province, People's Republic of China
| | - Yongxin Tao
- Pediatric Surgery, Children's Hospital of Changchun, Changchun, 130021, Jilin Province, People's Republic of China
| | - Chuibing Zhou
- Pediatric Surgery, Children's Hospital of Changchun, Changchun, 130021, Jilin Province, People's Republic of China
| | - Ruting Cui
- Pediatric Surgery, Children's Hospital of Changchun, Changchun, 130021, Jilin Province, People's Republic of China
| | - Jingying Li
- Pediatric Surgery, Children's Hospital of Changchun, Changchun, 130021, Jilin Province, People's Republic of China
| | - Rongpeng Han
- Pediatric Surgery, Children's Hospital of Changchun, No. 1321, Beian Road, Chaoyang District, Changchun, 130021, Jilin Province, People's Republic of China.
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Niu H, Guan Y, Zhong T, Ma L, Zayed M, Guan J. Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFβ pathways promote diabetic wound healing. NPJ Regen Med 2023; 8:32. [PMID: 37422462 PMCID: PMC10329719 DOI: 10.1038/s41536-023-00313-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 06/27/2023] [Indexed: 07/10/2023] Open
Abstract
Various therapies have been utilized for treating diabetic wounds, yet current regiments do not simultaneously address the key intrinsic causes of slow wound healing, i.e., abnormal skin cell functions (particularly migration), delayed angiogenesis, and chronic inflammation. To address this clinical gap, we develop a wound dressing that contains a peptide-based TGFβ receptor II inhibitor (PTβR2I), and a thermosensitive and reactive oxygen species (ROS)-scavenging hydrogel. The wound dressing can quickly solidify on the diabetic wounds following administration. The released PTβR2I inhibits the TGFβ1/p38 pathway, leading to improved cell migration and angiogenesis, and decreased inflammation. Meanwhile, the PTβR2I does not interfere with the TGFβ1/Smad2/3 pathway that is required to regulate myofibroblasts, a critical cell type for wound healing. The hydrogel's ability to scavenge ROS in diabetic wounds further decreases inflammation. Single-dose application of the wound dressing significantly accelerates wound healing with complete wound closure after 14 days. Overall, using wound dressings capable of adaptively modulating TGFβ pathways provides a new strategy for diabetic wound treatment.
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Affiliation(s)
- Hong Niu
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, USA
| | - Ya Guan
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, USA
- Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO, USA
| | - Ting Zhong
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, USA
| | - Liang Ma
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Mohamed Zayed
- Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, St. Louis, MO, USA
- Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA
| | - Jianjun Guan
- Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, USA.
- Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO, USA.
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
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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: 17] [Impact Index Per Article: 8.5] [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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Zheng SY, Wan XX, Kambey PA, Luo Y, Hu XM, Liu YF, Shan JQ, Chen YW, Xiong K. Therapeutic role of growth factors in treating diabetic wound. World J Diabetes 2023; 14:364-395. [PMID: 37122434 PMCID: PMC10130901 DOI: 10.4239/wjd.v14.i4.364] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/16/2023] [Accepted: 03/21/2023] [Indexed: 04/12/2023] Open
Abstract
Wounds in diabetic patients, especially diabetic foot ulcers, are more difficult to heal compared with normal wounds and can easily deteriorate, leading to amputation. Common treatments cannot heal diabetic wounds or control their many complications. Growth factors are found to play important roles in regulating complex diabetic wound healing. Different growth factors such as transforming growth factor beta 1, insulin-like growth factor, and vascular endothelial growth factor play different roles in diabetic wound healing. This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds. Further, some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors. The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.
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Affiliation(s)
- Shen-Yuan Zheng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
| | - Xin-Xing Wan
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
| | - Piniel Alphayo Kambey
- Department of Neurobiology and Anatomy, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
| | - Yan Luo
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Xi-Min Hu
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
| | - Yi-Fan Liu
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Jia-Qi Shan
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Yu-Wei Chen
- Clinical Medicine Eight-Year Program, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Kun Xiong
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
- Key Laboratory of Emergency and Trauma, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, Hainan Province, China
- Hunan Key Laboratory of Ophthalmology, Central South University, Changsha 410013, Hunan Province, China
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An Overview on Wound Dressings and Sutures Fabricated by Electrospinning. BIOTECHNOL BIOPROC E 2023. [DOI: 10.1007/s12257-021-0364-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2023]
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Hong J, Zheng W, Wang X, Hao Y, Cheng G. Biomedical polymer scaffolds mimicking bone marrow niches to advance in vitro expansion of hematopoietic stem cells. J Mater Chem B 2022; 10:9755-9769. [PMID: 36444902 DOI: 10.1039/d2tb01211a] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Hematopoietic stem cell (HSC) transplantation provides an effective platform for the treatment of hematological disorders. However, the donor shortage of HSCs and immune responses severely restrict the clinical applications of HSCs. Compared to allogeneic transplantation, autogenous transplantation poses less risk to the immune system, but the problem associated with insufficient HSCs remains a substantial challenge. A significant strategy for obtaining sufficient HSCs is to promote the expansion of HSCs. In vivo, a bone marrow microenvironment supports the survival and hematopoiesis of HSCs. Therefore, it is crucial to establish a platform that mimics the features of a bone marrow microenvironment for the in vitro expansion of HSCs. Three-dimensional (3D) scaffolds have emerged as the most powerful tools to mimic cellular microenvironments for the growth and proliferation of stem cells. Biomedical polymers have been widely utilized as cell scaffolds due to their advantageous features including favorable biocompatibility, biodegradability, as well as adjustable physical and chemical properties. This review focuses on recent advances in the study of biomedical polymer scaffolds that mimic bone marrow microenvironments for the in vitro expansion of HSCs. Bone marrow transplantation and microenvironments are first introduced. Then, biomedical polymer scaffolds for the expansion of HSCs and future prospects are summarized and discussed.
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Affiliation(s)
- Jing Hong
- Guangdong Institute of Semiconductor Micro-Nano Manufacturing Technology, Guangdong 528200, China.,CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Jiangsu 215123, China. .,School of Nano-Tech and Nano Bionics, University of Science and Technology of China, Anhui 230026, China
| | - Wenlong Zheng
- Suzhou Kowloon Hospital Shanghai Jiao Tong University School of Medicine, Jiangsu 215021, China
| | | | - Ying Hao
- Guangdong Institute of Semiconductor Micro-Nano Manufacturing Technology, Guangdong 528200, China.,CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Jiangsu 215123, China. .,School of Nano-Tech and Nano Bionics, University of Science and Technology of China, Anhui 230026, China
| | - Guosheng Cheng
- Guangdong Institute of Semiconductor Micro-Nano Manufacturing Technology, Guangdong 528200, China.,CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Jiangsu 215123, China. .,School of Nano-Tech and Nano Bionics, University of Science and Technology of China, Anhui 230026, China
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Astragalus Polysaccharides/PVA Nanofiber Membranes Containing Astragaloside IV-Loaded Liposomes and Their Potential Use for Wound Healing. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9716271. [PMID: 35600951 PMCID: PMC9117023 DOI: 10.1155/2022/9716271] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/13/2022] [Indexed: 12/24/2022]
Abstract
Delayed wound healing is a common and serious complication in diabetic patients, especially the slow healing of foot ulcers, which seriously affects the quality of life of patients and is also the most important risk factor for lower limb amputation. The multifunctional novel dressing prepared by loading the polymer nanofibers with anti-inflammatory and prohealing plant extracts can promote the wound repair of these ulcers by electrospinning technology. Liposomes are nanoparticles prepared from phospholipids and have been widely used as drug delivery systems. Liposomes can be combined with electrospun nanofibrous webs to facilitate local and sustained delivery of loaded bioactive substances. In this study, liposomes were prepared with astragaloside IV (AS) by employing a modified ethanol injection method and conducting the physical and chemical characterization (e.g., the particle size, polydispersity index, zeta potential, and entrapment efficiency). Astragalus polysaccharides were extracted from Astragalus membranaceus. Subsequently, we prepared the electrospun polyvinyl alcohol (PVA)/astragalus polysaccharide (APS)/astragaloside IV (AS) nanofibers. The morphology of the produced ASL/APS/PVA, APS/PVA, and PVA nanofibers were analyzed by scanning electron microscopy (SEM), and it turns out that the addition of astragalus extract made the fiber diameter smaller and the fibers arranged neatly with no dripping. An induced diabetic rat model was built, and a diabetic ulcer model was built by total cortical resection to assess the prorepair ability of the prepared nanofibers. According to in vivo animal experiments, the nanofibrous membrane loaded with APS and ASL was reported to inhibit the occurrence of wound inflammation, enhance the deposition of collagen fibers (P < 0.05) and the repair of regenerated epithelium (P < 0.05), and effectively strengthen the wound healing of diabetic rats (P < 0.05). In brief, PVA-loaded APS/ASL nanofibrous membranes refer to a prominent wound healing dressing material, which can effectively facilitate the healing of diabetic wounds, and they are demonstrated to be highly promising for application in diabetic wound dressings and tissue engineering.
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Al-Otaibi AM, Al-Gebaly AS, Almeer R, Albasher G, Al-Qahtani WS, Abdel Moneim AE. Melatonin pre-treated bone marrow derived-mesenchymal stem cells prompt wound healing in rat models. Biomed Pharmacother 2022; 145:112473. [PMID: 34861635 DOI: 10.1016/j.biopha.2021.112473] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/16/2021] [Accepted: 11/23/2021] [Indexed: 01/16/2023] Open
Abstract
Bone marrow derived-mesenchymal stem cells (BMSCs)-based therapy is an outstanding candidate for cutaneous wound healing. Melatonin (MEL) has been reported for its anti-inflammatory as well as tissue regenerative properties. Existing work aimed to explore the potential healing power of BMSCs pre-treated with MEL in a skin wound model. Adult rats were allocated into control, PIO, BMSCs (1 × 105 cells), and MEL/BMSCs groups. On the 21 days post-wounding, tissues were sampled for analysis. The results demonstrated that compared to the control group, MEL/BMSCs therapy induced noticeable decline in wound area and elevated rate of wound retraction. Furthermore, marked increases in tissue hydroxyproline, as well as tissue content and gene expression level of vascular endothelial growth factor in MEL/BMSCs treated-wounded animals. Compared to the untreated control group, marked increases were found in antioxidant enzymatic activities together with elevated GSH levels in wounded tissues after MEL/BMSCs treatment. Moreover, therapeutically handled wounds with MEL/BMSCs revealed low levels of MDA, NO and protein carbonyls. Combined therapy with MEL/BMSCs relieved the inflammation witnessed by decreasing IL-1β, TNF-α and NF-κB levels in wounded tissues. Furthermore, noteworthy rises in levels of TGF-β and gene expression of α-SMA were noticed after MEL/BMSCs application that reveals their anti-scarring properties. Histologically, noticeable improvement in histopathological skin lesions in wound area and elevated the collagen synthesis and deposition. Collectively, the obtained data depict that the pre-treatment of BMSCs with MEL could potentially be a successful strategy for scaling-up the wound healing outcomes more than using BMSCs monotherapy in rat models.
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Affiliation(s)
- Aljohara M Al-Otaibi
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Asma S Al-Gebaly
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Rafa Almeer
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Gadah Albasher
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Wedad S Al-Qahtani
- Department of Forensic Sciences, College of Forensic Justice, Naif Arab University for Security Sciences, Riyadh, Saudi Arabia
| | - Ahmed E Abdel Moneim
- Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt.
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Golledge J, Thanigaimani S. Novel therapeutic targets for diabetes-related wounds or ulcers: an update on preclinical and clinical research. Expert Opin Ther Targets 2021; 25:1061-1075. [PMID: 34873970 DOI: 10.1080/14728222.2021.2014816] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Diabetes-related wounds, particularly diabetes-related foot ulcers, are mainly caused by lack of foot sensation and high plantar tissue stress secondary to peripheral neuropathy, ischemia secondary to peripheral artery disease, and dysfunctional wound healing. Current management of diabetes-related wounds involves the offloading of high foot pressures and the treatment of ischemia through revascularization. Despite these treatments, the global burden of diabetes-related wounds is growing, and thus, novel therapies are needed. The normal wound healing process is a coordinated remodeling process orchestrated by fibroblasts, endothelial cells, phagocytes, and platelets, controlled by an array of growth factors. In diabetes-related wounds, these coordinated processes are dysfunctional. The past animal model and human research suggest that prolonged wound inflammation, failure to adequately correct ischemia, and impaired wound maturation are key therapeutic targets to improve diabetes-related wound healing. AREAS COVERED This review summarizes recent preclinical and clinical research on novel diabetes-related wound treatments. Animal models of diabetes-related wounds and recent studies testing novel therapeutic agents in these models are described. Findings from clinical trials are also discussed. Finally, challenges to identifying and implementing novel therapies are described. EXPERT OPINION Given the growing volume of promising drug therapies currently under investigation, it is expected within the next decade, that diabetes-related wound treatment will be transformed.
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Affiliation(s)
- Jonathan Golledge
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.,The Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia.,The Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
| | - Shivshankar Thanigaimani
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.,The Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
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12
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Bhar B, Chouhan D, Pai N, Mandal BB. Harnessing Multifaceted Next-Generation Technologies for Improved Skin Wound Healing. ACS APPLIED BIO MATERIALS 2021; 4:7738-7763. [PMID: 35006758 DOI: 10.1021/acsabm.1c00880] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Dysregulation of sequential and synchronized events of skin regeneration often results in the impairment of chronic wounds. Conventional wound dressings fail to trigger the normal healing mechanism owing to the pathophysiological conditions. Tissue engineering approaches that deal with the fabrication of dressings using various biomaterials, growth factors, and stem cells have shown accelerated healing outcomes. However, most of these technologies are associated with difficulties in scalability and cost-effectiveness of the products. In this review, we survey the latest developments in wound healing strategies that have recently emerged through the multidisciplinary approaches of bioengineering, nanotechnology, 3D bioprinting, and similar cutting-edge technologies to overcome the limitations of conventional therapies. We also focus on the potential of wearable technology that supports complete monitoring of the changes occurring in the wound microenvironment. In addition, we review the role of advanced devices that can precisely enable the delivery of nanotherapeutics, oligonucleotides, and external stimuli in a controlled manner. These technological advancements offer the opportunity to actively influence the regeneration process to benefit the treatment regime further. Finally, the clinical relevance, trajectory, and prospects of this field have been discussed in brief that highlights their potential in providing a beneficial wound care solution at an affordable cost.
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Affiliation(s)
- Bibrita Bhar
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Dimple Chouhan
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Nakhul Pai
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Biman B Mandal
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.,Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.,School of Health Science and Technology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
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13
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Maleki H, Khoshnevisan K, Sajjadi-Jazi SM, Baharifar H, Doostan M, Khoshnevisan N, Sharifi F. Nanofiber-based systems intended for diabetes. J Nanobiotechnology 2021; 19:317. [PMID: 34641920 PMCID: PMC8513238 DOI: 10.1186/s12951-021-01065-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 09/28/2021] [Indexed: 01/01/2023] Open
Abstract
Diabetic mellitus (DM) is the most communal metabolic disease resulting from a defect in insulin secretion, causing hyperglycemia by promoting the progressive destruction of pancreatic β cells. This autoimmune disease causes many severe disorders leading to organ failure, lower extremity amputations, and ultimately death. Modern delivery systems e.g., nanofiber (NF)-based systems fabricated by natural and synthetic or both materials to deliver therapeutics agents and cells, could be the harbinger of a new era to obviate DM complications. Such delivery systems can effectively deliver macromolecules (insulin) and small molecules. Besides, NF scaffolds can provide an ideal microenvironment to cell therapy for pancreatic β cell transplantation and pancreatic tissue engineering. Numerous studies indicated the potential usage of therapeutics/cells-incorporated NF mats to proliferate/regenerate/remodeling the structural and functional properties of diabetic skin ulcers. Thus, we intended to discuss the aforementioned features of the NF system for DM complications in detail.
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Affiliation(s)
- Hassan Maleki
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Research and Development Team, Evolution Wound Dressing (EWD) Startup Co., Tehran, Iran.
| | - Kamyar Khoshnevisan
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Research and Development Team, Evolution Wound Dressing (EWD) Startup Co., Tehran, Iran.
| | - Sayed Mahmoud Sajjadi-Jazi
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, 1411713137, Tehran, Iran
- Research and Development Team, Evolution Wound Dressing (EWD) Startup Co., Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, 1411713137, Tehran, Iran
| | - Hadi Baharifar
- Department of Medical Nanotechnology, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, 1477893855, Tehran, Iran
- Research and Development Team, Evolution Wound Dressing (EWD) Startup Co., Tehran, Iran
| | - Maryam Doostan
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nazanin Khoshnevisan
- Research and Development Team, Evolution Wound Dressing (EWD) Startup Co., Tehran, Iran
| | - Farshad Sharifi
- Research and Development Team, Evolution Wound Dressing (EWD) Startup Co., Tehran, Iran
- Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, 1411713137, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, 1411713137, Tehran, Iran
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14
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Khan AUR, Morsi Y, Zhu T, Ahmad A, Xie X, Yu F, Mo X. Electrospinning: An emerging technology to construct polymer-based nanofibrous scaffolds for diabetic wound healing. FRONTIERS OF MATERIALS SCIENCE 2021; 15:10-35. [DOI: 10.1007/s11706-021-0540-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 11/23/2020] [Indexed: 01/05/2025]
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15
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Khan AUR, Huang K, Khalaji MS, Yu F, Xie X, Zhu T, Morsi Y, Jinzhong Z, Mo X. Multifunctional bioactive core-shell electrospun membrane capable to terminate inflammatory cycle and promote angiogenesis in diabetic wound. Bioact Mater 2021; 6:2783-2800. [PMID: 33665509 PMCID: PMC7900605 DOI: 10.1016/j.bioactmat.2021.01.040] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 01/25/2021] [Accepted: 01/31/2021] [Indexed: 12/21/2022] Open
Abstract
Diabetic wound (DW) healing is a major clinical challenge due to multifactorial complications leading to prolonged inflammation. Electrospun nanofibrous (NF) membranes, due to special structural features, are promising biomaterials capable to promote DW healing through the delivery of active agents in a controlled manner. Herein, we report a multifunctional composite NF membrane loaded with ZnO nanoparticles (NP) and oregano essential oil (OEO), employing a new loading strategy, capable to sustainedly co-deliver bioactive agents. Physicochemical characterization revealed the successful fabrication of loaded nanofibers with strong in vitro anti-bacterial and anti-oxidant activities. Furthermore, in vivo wound healing confirmed the potential of bioactive NF membranes in epithelialization and granulation tissue formation. The angiogenesis was greatly prompted by the bioactive NF membranes through expression of vascular endothelial growth factor (VEGF). Moreover, the proposed NF membrane successfully terminated the inflammatory cycle by downregulating the pro-inflammatory cytokines interleukin −6 (IL-6) and matrix metalloproteinases-9 (MMP-9). In vitro and in vivo studies revealed the proposed NF membrane is a promising dressing material for the healing of DW.
A modified loading strategy was employed for dual bioactive agents through electrospinning. The nanofibers sustainedly released the two bioactive agents. The fabricated bioactive membranes turned out to be biocompatible, antioxidant and antibacterial. The proposed bioactive membranes have posesses the potential of healing diabetic wounds.
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Affiliation(s)
- Atta Ur Rehman Khan
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, PR China
| | - Kai Huang
- Department of Sports Medicine, Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, PR China
| | - Mina Shahriari Khalaji
- Microbiological Engineering and Industrial Biotechnology Group, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, PR China
| | - Fan Yu
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, PR China
| | - Xianrui Xie
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, PR China
| | - Tonghe Zhu
- Multidisciplinary Centre for Advanced Materials of Shanghai University of Engineering Science, College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, No. 333 Longteng Road, Shanghai, 201620, PR China
| | - Yosry Morsi
- Faculty of Engineering and Industrial Sciences, Swinburne University of Technology, Boroondara, VIC, 3122, Australia
| | - Zhao Jinzhong
- Department of Sports Medicine, Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, PR China
| | - Xiumei Mo
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, PR China
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16
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17
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Khoobi MM, Naddaf H, Hoveizi E, Mohammadi T. Silymarin effect on experimental bone defect repair in rat following implantation of the electrospun PLA/carbon nanotubes scaffold associated with Wharton's jelly mesenchymal stem cells. J Biomed Mater Res A 2020; 108:1944-1954. [PMID: 32323447 DOI: 10.1002/jbm.a.36957] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 03/19/2020] [Accepted: 03/28/2020] [Indexed: 01/11/2023]
Abstract
In this study, the ability of silymarin to heal rat calvarial bone critical defects with mesenchymal stem cells isolated from human Wharton's jelly (HWJMSC) cultured on the electrospun scaffold of poly (lactic acid)/carbon nanotube (PLA/CNT) has been examined. In this study, 20 adult male Wistar rats were divided into four groups of five each. Under general anesthesia, 8 mm defects were created in the calvarial bone of the rats. Then, study groups were defined as no treatment group, the scaffold alone, the scaffold and HWJMSCs, and the scaffold/cells plus oral silymarin, respectively. The histomorphometric study was performed using H&E staining and Goldner's Masson trichrome as specific staining. The results of this study showed that the electrospun PLA/CNT scaffold is a biocompatible scaffold and HWJMSCs can considerably attach and proliferate on this scaffold, and the scaffold itself is also a suitable option for improving the bone repair process. The results of the histomorphometric analysis also showed a significantly higher amount of recently formed bone in the silymarin group plus scaffold/cells compared to the scaffold and cell group alone (p < .05). Utilizing silymarin plus HWJMSCs cultured on PLA/CNT scaffold can be used as a suitable method for the process of osteogenesis and bone repair.
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Affiliation(s)
- Mohammad Mohsen Khoobi
- Department of Clinical Sciences, Faculty of Veterinary, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Hadi Naddaf
- Department of Clinical Sciences, Faculty of Veterinary, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Elham Hoveizi
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Tayebeh Mohammadi
- Department of Basic Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran
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