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Wang J, Liu H, Liu M, Shen T, Weng T, He F, Wang X. A dual gene-activated dermal scaffolds loaded with nanocomposite particles expressing of VEGF and aFGF: Promoting wound healing by early vascularization. Int J Biol Macromol 2025; 307:141831. [PMID: 40057066 DOI: 10.1016/j.ijbiomac.2025.141831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/23/2025] [Accepted: 03/05/2025] [Indexed: 03/16/2025]
Abstract
The urgent need to enhance the early vascularization of dermal substitutes to improve their repair efficiency in skin defect wound presents a significant challenge. This study investigated the impact of dual gene-activated scaffolds (DGAS-M), which combined nanocomposite particles (NPs) encapsulating plasmid DNA (pDNA) of VEGF and aFGF, with the aim of enhancing early vascularization and vascular maturation. In this study, we used the liposomes to encapsulate pDNA and loaded on PLGA knitted mesh-reinforced collagen/chitosan scaffolds (PLGAm/CCS) to prepare DGAS-M. DGAS-M exerted effects on the proliferation of human fibroblasts, angiogenesis, and the synthesis and secretion of growth factors in umbilical vein endothelial cells in vitro. Furthermore, in a rat full-thickness skin defect model, DGAS-M enhanced the survival rate of autologous split-thickness skin grafts during the first 14 days post-surgery. DGAS-M not only accelerated the vascularization process in the wound but also promoted collagen deposition while diminishing the release of inflammatory mediators, ultimately improving the quality of healing. This approach offers a potential solution to address the present clinical problem of skin defect recovery.
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Affiliation(s)
- Jialiang Wang
- Department of Burns & Wound Care Center, Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou 310009, China; Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue, Zhejiang university, Hangzhou 310009, China
| | - Huan Liu
- Department of Burns & Wound Care Center, Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou 310009, China; Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue, Zhejiang university, Hangzhou 310009, China
| | - Meixuan Liu
- Department of Burns & Wound Care Center, Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou 310009, China; Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue, Zhejiang university, Hangzhou 310009, China
| | - Tao Shen
- Department of Burns & Wound Care Center, Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou 310009, China; Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue, Zhejiang university, Hangzhou 310009, China
| | - Tingting Weng
- Department of Burn and Plastic Surgery, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China; National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.
| | - Fang He
- Department of Burns & Wound Care Center, Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou 310009, China; Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue, Zhejiang university, Hangzhou 310009, China.
| | - Xingang Wang
- Department of Burns & Wound Care Center, Second Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou 310009, China; Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue, Zhejiang university, Hangzhou 310009, China.
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2
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van den Bosch AS, Verwilligen RAF, Pijpe A, Jansen LB, van der Vlies CH, van Eck ME, Burchell GL, van Zuijlen PPM, Middelkoop E. Indications for the use of dermal substitutes in patients with acute burns and in reconstructive surgery after burns: A systematic review. Wound Repair Regen 2025; 33:e13248. [PMID: 39727218 PMCID: PMC11672668 DOI: 10.1111/wrr.13248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/10/2024] [Indexed: 12/28/2024]
Abstract
Deep dermal and full-thickness burns often result in scar sequelae such as contractures, hypertrophy, pain and itching following split-thickness skin grafting. Dermal substitutes are currently employed alongside split-thickness skin grafting to enhance clinical outcomes, though their indications remain a subject of ongoing debate. This systematic review aims to clarify the indications for the application of dermal substitutes in burn patients, in both acute and reconstructive settings. A comprehensive search across various databases was conducted. Studies (n = 190) assessing the indications and outcomes of dermal substitutes in acute burn patients and those requiring reconstructive surgery were included. Data extraction included the applied dermal substitute, age, total body surface area, wound depth, burn aetiology, anatomical site and exclusion criteria. The indications were derived from predetermined indications, i.e. inclusion and exclusion criteria and patient characteristics. The depth of the wound emerged as the primary indication for dermal substitute use. A one-stage approach is recommended for deep dermal to full-thickness wounds larger than 10 cm2, while a two-stage approach is advised for wounds of this depth with limited donor sites or exposed bone or tendon. No definitive age or burn/scar location thresholds were identified, and careful consideration is advised for electrical and chemical burns. Contraindications include wound infections and allergies to matrix components. Limited data exist on use in patients with diabetes mellitus, chronic vascular disease, or immunocompromised status. This is the first review to address the indications for dermal substitutes in burn patients, providing valuable insights for the development of international evidence-based treatment guidelines.
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Affiliation(s)
- Anna S. van den Bosch
- Alliance of Dutch Burn Care (ADBC), Burn CentreRed Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and RegenerationAmsterdam UMCAmsterdamThe Netherlands
| | - Robin A. F. Verwilligen
- Alliance of Dutch Burn Care (ADBC), Burn CentreRed Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and RegenerationAmsterdam UMCAmsterdamThe Netherlands
| | - Anouk Pijpe
- Alliance of Dutch Burn Care (ADBC), Burn CentreRed Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and RegenerationAmsterdam UMCAmsterdamThe Netherlands
| | - Lex B. Jansen
- Alliance of Dutch Burn Care (ADBC), Burn CentreRed Cross HospitalBeverwijkThe Netherlands
| | - Cornelis H. van der Vlies
- Alliance of Dutch Burn Care (ADBC), Burn CentreMaasstad HospitalRotterdamThe Netherlands
- Department of Trauma and Burn SurgeryMaasstad HospitalRotterdamThe Netherlands
- Trauma Research Unit, Department of Surgery, Erasmus MCUniversity Medical CentreRotterdamThe Netherlands
| | - Merit E. van Eck
- Alliance of Dutch Burn Care (ADBC), Burn CentreMartini HospitalGroningenThe Netherlands
| | | | - Paul P. M. van Zuijlen
- Alliance of Dutch Burn Care (ADBC), Burn CentreRed Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and RegenerationAmsterdam UMCAmsterdamThe Netherlands
- Pediatric Surgical Centre, Emma Children's HospitalAmsterdam UMCAmsterdamThe Netherlands
| | - Esther Middelkoop
- Alliance of Dutch Burn Care (ADBC), Burn CentreRed Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and RegenerationAmsterdam UMCAmsterdamThe Netherlands
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Dilek ÖF, Sevim KZ, Dilek ON. Acellular dermal matrices in reconstructive surgery; history, current implications and future perspectives for surgeons. World J Clin Cases 2024; 12:6791-6807. [PMID: 39687641 PMCID: PMC11525903 DOI: 10.12998/wjcc.v12.i35.6791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 10/03/2024] [Accepted: 10/15/2024] [Indexed: 10/24/2024] Open
Abstract
Large-scale defects of body in the reconstructive surgical practice, and the helplessness of their repair with autologous tissues, have been an important factor in the development of artificial biological products for the temporary, definitive, or staged repair of these defects. A major advance in the field of plastic and other reconstructive surgery in this regard has been the introduction and successful use of acellular dermal matrices (ADMs). In recent years, not only the type of tissue from which ADMs are produced, product range, diversity and areas of use have increased, but their use in reconstructive fields, especially in post oncologic breast surgery, has become highly regarded and this has favored ADMs to be a potential cornerstone in specific and well-defined surgical fields in future. It is essential that reconstructive surgeons become familiar with some of the ADM's as well as the advantages and limitations to their use. This review not only provides basic science and clinical evidence of the current use of ADMs in wide range of surgical fields but also targets to keep them as an important backdrop in the armamentarium of reconstructive surgeons. Brief considerations of possible future directions for ADMs are also conducted in the end.
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Affiliation(s)
- Ömer F Dilek
- Department of Plastic, Reconstructive and Aesthetic Surgery, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul 34396, Türkiye
| | - Kamuran Z Sevim
- Department of Plastic and Reconstructive Surgery, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul 34396, Türkiye
| | - Osman N Dilek
- Department of Surgery, İzmir Katip Celebi University, School of Medicine, İzmir 35150, Türkiye
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van den Bosch AS, Verwilligen RAF, Pijpe A, Bosma E, van der Vlies CH, Lucas Y, Burchell GL, van Zuijlen PPM, Middelkoop E. Outcomes of dermal substitutes in burns and burn scar reconstruction: A systematic review and meta-analysis. Wound Repair Regen 2024; 32:960-978. [PMID: 39435560 PMCID: PMC11584356 DOI: 10.1111/wrr.13226] [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: 06/18/2024] [Revised: 08/06/2024] [Accepted: 09/15/2024] [Indexed: 10/23/2024]
Abstract
Dermal substitutes have been introduced in burn care to improve wound healing outcomes; however, their use remains limited in standard treatments. This systematic review and meta-analysis aimed to evaluate the outcomes of dermal substitutes in patients with burns and patients requiring burn scar reconstruction and subsequently contribute to optimising the integration of dermal substitutes into clinical practice and reducing the knowledge gap. A comprehensive search across various databases included human studies from peer-reviewed journals on dermal substitutes for deep dermal and full-thickness burns, and scar reconstruction across all ages. Data from comparative trials were extracted, focusing on patient and wound characteristics, treatment specifics, and outcomes related to wound healing and scar quality. Meta-analysis was performed on trials reporting similar post-burn measures, with statistical heterogeneity assessed. Outcomes were presented using mean differences or odds ratios with 95% confidence intervals. A total of 31 comparative trials were included. The overall quality of the studies was considered moderate. The meta-analysis indicated delayed re-epithelialization 4-7 days after treatment with a collagen-elastin matrix compared to split-thickness skin graft in acute burns (-7.30%, p = 0.02). Significant improvement in subjective scar quality was observed with acellular dermal matrix compared to split-thickness skin graft in acute burn wounds 6 months post-operative (-1.95, p <0.01). While acknowledging the initially delayed wound healing, incorporating dermal substitutes into the surgical treatment of burn patients holds promise for enhancing scar quality. However, future research must prioritise outcome measure uniformity, address variations in dermal substitute application, and standardise indications for consistent and effective practices.
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Affiliation(s)
- Anna S. van den Bosch
- Alliance of Dutch Burn Care (ADBC), Burn Centre, Red Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and Regeneration, Amsterdam UMCAmsterdamThe Netherlands
| | - Robin A. F. Verwilligen
- Alliance of Dutch Burn Care (ADBC), Burn Centre, Red Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and Regeneration, Amsterdam UMCAmsterdamThe Netherlands
| | - Anouk Pijpe
- Alliance of Dutch Burn Care (ADBC), Burn Centre, Red Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and Regeneration, Amsterdam UMCAmsterdamThe Netherlands
| | - Eelke Bosma
- Alliance of Dutch Burn Care (ADBC), Burn Centre, Martini HospitalGroningenThe Netherlands
- Department of Surgery, Martini HospitalGroningenThe Netherlands
| | - Cees H. van der Vlies
- Alliance of Dutch Burn Care (ADBC), Burn Centre, Maasstad HospitalRotterdamThe Netherlands
- Departments of Trauma and Burn Surgery, Maasstad HospitalRotterdamThe Netherlands
- Trauma Research Unit, Department of Surgery, Erasmus MCUniversity Medical Centre RotterdamRotterdamThe Netherlands
| | - Ymke Lucas
- Alliance of Dutch Burn Care (ADBC), Burn Centre, Maasstad HospitalRotterdamThe Netherlands
| | - George L. Burchell
- Amsterdam UMC location Vrije Universiteit AmsterdamUniversity LibraryAmsterdamThe Netherlands
| | - Paul P. M. van Zuijlen
- Alliance of Dutch Burn Care (ADBC), Burn Centre, Red Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and Regeneration, Amsterdam UMCAmsterdamThe Netherlands
- Pediatric Surgical Centre, Emma Children's Hospital, Amsterdam UMCAmsterdamThe Netherlands
| | - Esther Middelkoop
- Alliance of Dutch Burn Care (ADBC), Burn Centre, Red Cross HospitalBeverwijkThe Netherlands
- Department of Plastic, Reconstructive & Hand SurgeryAmsterdam UMC Location Vrije Universiteit AmsterdamAmsterdamThe Netherlands
- Amsterdam Movement Sciences, Tissue Function and Regeneration, Amsterdam UMCAmsterdamThe Netherlands
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Wang X, Guo J, Yu Q, Zhao L, Gao X, Wang L, Wen M, Yan J, An M, Liu Y. Decellularized Matrices for the Treatment of Tissue Defects: from Matrix Origin to Immunological Mechanisms. Biomol Ther (Seoul) 2024; 32:509-522. [PMID: 39091238 PMCID: PMC11392660 DOI: 10.4062/biomolther.2024.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 05/07/2024] [Accepted: 05/31/2024] [Indexed: 08/04/2024] Open
Abstract
Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-β/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.
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Affiliation(s)
- Xinyue Wang
- Institute of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Shanxi 030024, China
| | - Jiqiang Guo
- Institute of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Shanxi 030024, China
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Qing Yu
- Institute of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Shanxi 030024, China
| | - Luyao Zhao
- Institute of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Shanxi 030024, China
| | - Xiang Gao
- Institute of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Shanxi 030024, China
| | - Li Wang
- Institute of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Shanxi 030024, China
| | - Meiling Wen
- Institute of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Shanxi 030024, China
| | - Junrong Yan
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China
| | - Meiwen An
- Institute of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Shanxi 030024, China
| | - Yang Liu
- Institute of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Shanxi 030024, China
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan 030001, China
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Chen L, Yang J, Wang D, Jiang J, Zhang B, Zhao Z, Chen X, Lv D. Multicenter effect analysis of one-step acellular dermis combined with autologous ultra-thin split thickness skin composite transplantation in treating burn and traumatic wounds. Int Wound J 2024; 21:e14341. [PMID: 37548136 PMCID: PMC10777748 DOI: 10.1111/iwj.14341] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/11/2023] [Accepted: 07/12/2023] [Indexed: 08/08/2023] Open
Abstract
To evaluate the efficacy of one-step acellular dermis combined with autologous split thickness skin grafting in the treatment of burn or trauma wounds by a multicenter controlled study. In patients with extensive burns, it is even difficult to repair the wounds due to the shortage of autologous skin. The traditional skin grafting method has the disadvantages of large damage to the donor site, insufficient skin source and unsatisfactory appearance, wear resistance and elasticity of the wound tissue after skin grafting. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft can achieve better healing effect in the treatment of burn and trauma wounds. A total of 1208 patients who underwent single-layer skin grafting and one-step composite skin grafting in the First Affiliated Hospital of Wannan Medical College, Wuhan Third People's Hospital and Lu 'an People's Hospital from 2019 to 2022 were retrospectively analysed. The total hospitalization cost, total operation cost, hospitalization days after surgery, wound healing rate after 1 week of skin grafting and scar follow-up at 6 months after discharge were compared and studied. The total cost of hospitalization and operation in the composite skin grafting group was significantly higher than those in the single-layer autologous skin grafting group. The wound healing rate after 1 week of skin grafting and the VSS score of scar in the follow-up of 6 months after discharge were better than those in the single-layer skin grafting group. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft has high wound healing rate, less scar, smooth appearance and good elasticity in repairing burn and trauma wounds, which can provide an ideal repair method for wounds.
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Affiliation(s)
- Lei Chen
- Department of Burn and Plastic SurgeryFirst Affiliated Hospital of Wannan Medical CollegeWuhuPR China
- Department of BurnsFirst Affiliated Hospital of Anhui Medical UniversityHefeiPR China
| | - Jing Yang
- Department of Burn and Plastic SurgeryFirst Affiliated Hospital of Wannan Medical CollegeWuhuPR China
| | - De‐yun Wang
- Department of Burn and Plastic SurgeryWuhan Third HospitalWuhanPR China
| | - Jun‐mei Jiang
- Department of Burn and Plastic SurgeryWuhan Third HospitalWuhanPR China
| | - Bao‐de Zhang
- Department of Burn and Plastic SurgeryLu'an People's HospitalLu'anPR China
| | - Zun‐jiang Zhao
- Department of Burn and Plastic SurgeryFirst Affiliated Hospital of Wannan Medical CollegeWuhuPR China
| | - Xu‐Lin Chen
- Department of BurnsFirst Affiliated Hospital of Anhui Medical UniversityHefeiPR China
| | - Da‐lun Lv
- Department of Burn and Plastic SurgeryFirst Affiliated Hospital of Wannan Medical CollegeWuhuPR China
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