Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction

Tissue engineering strategies hold promise for constructing biomimetic tracheal substitutes to repair circumferential tracheal defects. However, current strategies for constructing off-the-shelf cartilage analogs for artificial trachea grafts face challenges of chondrocyte scarcity and inadequate cu...

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Main Authors: Yaqiang Li, Xiaowei Xun, Liang Duan, Erji Gao, Jiaxin Li, Lei Lin, Xinping Li, Aijuan He, Haiyong Ao, Yong Xu, Huitang Xia
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-05-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25000076
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author Yaqiang Li
Xiaowei Xun
Liang Duan
Erji Gao
Jiaxin Li
Lei Lin
Xinping Li
Aijuan He
Haiyong Ao
Yong Xu
Huitang Xia
author_facet Yaqiang Li
Xiaowei Xun
Liang Duan
Erji Gao
Jiaxin Li
Lei Lin
Xinping Li
Aijuan He
Haiyong Ao
Yong Xu
Huitang Xia
author_sort Yaqiang Li
collection DOAJ
description Tissue engineering strategies hold promise for constructing biomimetic tracheal substitutes to repair circumferential tracheal defects. However, current strategies for constructing off-the-shelf cartilage analogs for artificial trachea grafts face challenges of chondrocyte scarcity and inadequate culture strategies, which require extensive cell expansion and prolonged in vitro culture to generate robust neo-cartilage. To address these issues, we developed a nanofiber-hydrogel composite with superior mechanical performance by incorporating fragment oxidized bacterial cellulose (BC) nanofibers into a gelatin methacryloyl (GelMA) hydrogel network. Additionally, a biomaterial system was developed based on this composite, featuring dual-release functionality of fibroblast growth factor (FGF) and transforming growth factor beta (TGF-β) to facilitate step-wise maturation of neo-cartilage tissue. This process includes early-stage proliferation followed by second-stage extracellular matrix (ECM) deposition, driving the transition from proliferation to chondrogenesis. By encapsulating chondrocytes within the biomaterial system, mature neo-cartilage tissues with typical cartilage lacunae structures and abundant homogeneous cartilage-specific ECM deposition were successfully regenerated in vitro and in vivo. Furthermore, with a tailor-made growth factor-releasing strategy, the biomaterial system with low cell seeding density achieved biochemically and biomechanically functional neo-cartilage tissue regeneration, comparable to that achieved with high cell seeding density in the nanofiber-hydrogel composite. Based on the current biomaterial system, mature and functional cartilage-ring analogs were successfully constructed and applied to repair tracheal defects. Overall, the biomaterial system developed in this study provides a promising strategy for engineering transplantable, high-quality cartilage substitutes, with translational potential for artificial trachea construction.
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spelling doaj-art-1265963ac4c541dab29cab78e41bfa1c2025-01-21T04:13:16ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-05-0147136151Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal constructionYaqiang Li0Xiaowei Xun1Liang Duan2Erji Gao3Jiaxin Li4Lei Lin5Xinping Li6Aijuan He7Haiyong Ao8Yong Xu9Huitang Xia10Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200430, ChinaSchool of Materials Science and Engineering, East China Jiaotong University, Nanchang, 330013, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200430, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200430, ChinaDepartment of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200430, ChinaDepartment of Thyroid Center, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, ChinaDepartment of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China; Corresponding author.School of Materials Science and Engineering, East China Jiaotong University, Nanchang, 330013, China; Corresponding author.Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200430, China; Department of Plastic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China; Corresponding author. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200430, China.Corresponding author. Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China.; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200430, China; School of Materials Science and Engineering, East China Jiaotong University, Nanchang, 330013, China; Department of Plastic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China; Department of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, China; Department of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China; Department of Thyroid Center, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China; Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China; Jinan Clinical Research Center for Tissue Engineering Skin Regeneration and Wound Repair, Jinan, Shandong, 250014, ChinaTissue engineering strategies hold promise for constructing biomimetic tracheal substitutes to repair circumferential tracheal defects. However, current strategies for constructing off-the-shelf cartilage analogs for artificial trachea grafts face challenges of chondrocyte scarcity and inadequate culture strategies, which require extensive cell expansion and prolonged in vitro culture to generate robust neo-cartilage. To address these issues, we developed a nanofiber-hydrogel composite with superior mechanical performance by incorporating fragment oxidized bacterial cellulose (BC) nanofibers into a gelatin methacryloyl (GelMA) hydrogel network. Additionally, a biomaterial system was developed based on this composite, featuring dual-release functionality of fibroblast growth factor (FGF) and transforming growth factor beta (TGF-β) to facilitate step-wise maturation of neo-cartilage tissue. This process includes early-stage proliferation followed by second-stage extracellular matrix (ECM) deposition, driving the transition from proliferation to chondrogenesis. By encapsulating chondrocytes within the biomaterial system, mature neo-cartilage tissues with typical cartilage lacunae structures and abundant homogeneous cartilage-specific ECM deposition were successfully regenerated in vitro and in vivo. Furthermore, with a tailor-made growth factor-releasing strategy, the biomaterial system with low cell seeding density achieved biochemically and biomechanically functional neo-cartilage tissue regeneration, comparable to that achieved with high cell seeding density in the nanofiber-hydrogel composite. Based on the current biomaterial system, mature and functional cartilage-ring analogs were successfully constructed and applied to repair tracheal defects. Overall, the biomaterial system developed in this study provides a promising strategy for engineering transplantable, high-quality cartilage substitutes, with translational potential for artificial trachea construction.http://www.sciencedirect.com/science/article/pii/S2452199X25000076Cartilage tissue engineeringHydrogelBacterial celluloseGrowth factorTissue-engineered trachea
spellingShingle Yaqiang Li
Xiaowei Xun
Liang Duan
Erji Gao
Jiaxin Li
Lei Lin
Xinping Li
Aijuan He
Haiyong Ao
Yong Xu
Huitang Xia
Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction
Bioactive Materials
Cartilage tissue engineering
Hydrogel
Bacterial cellulose
Growth factor
Tissue-engineered trachea
title Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction
title_full Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction
title_fullStr Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction
title_full_unstemmed Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction
title_short Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction
title_sort cartilage structure inspired nanofiber hydrogel composite with robust proliferation and stable chondral lineage specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction
topic Cartilage tissue engineering
Hydrogel
Bacterial cellulose
Growth factor
Tissue-engineered trachea
url http://www.sciencedirect.com/science/article/pii/S2452199X25000076
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