Xanthohumol bulk-modified polyurethane for tracheal repair: A ′killing two birds with one stone' strategy for tailorable mechanics and durable anti-inflammatory efficacy

Restoring tracheal defects remains a significant challenge in tissue engineering and regenerative medicine. Current scaffolds fall short of achieving optimal tracheal repair due to unmatched mechanical properties and limited anti‐inflammatory properties. In this study, we incorporated the natural pl...

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Main Authors: Siqiang Zheng, Li Xu, Qitao Bo, Erji Gao, Enkuo Zheng, Lei Xie, Bin Zhao, Jiaoyu Yi, Yang Li, Yong Xu, Yao Wang, Bo Tao
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425003916
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author Siqiang Zheng
Li Xu
Qitao Bo
Erji Gao
Enkuo Zheng
Lei Xie
Bin Zhao
Jiaoyu Yi
Yang Li
Yong Xu
Yao Wang
Bo Tao
author_facet Siqiang Zheng
Li Xu
Qitao Bo
Erji Gao
Enkuo Zheng
Lei Xie
Bin Zhao
Jiaoyu Yi
Yang Li
Yong Xu
Yao Wang
Bo Tao
author_sort Siqiang Zheng
collection DOAJ
description Restoring tracheal defects remains a significant challenge in tissue engineering and regenerative medicine. Current scaffolds fall short of achieving optimal tracheal repair due to unmatched mechanical properties and limited anti‐inflammatory properties. In this study, we incorporated the natural plant‐derived anti-inflammatory molecule Xanthohumol (XN) into the backbone of a degradable polyurethane (PEUU) to create a porous PEXUU scaffold with tailorable mechanical properties and sustained anti‐inflammatory activity. Materials Studio software was initially employed to simulate the feasibility of synthesizing the PEXUU elastomer using XN as a chain extender and poly(ε‐caprolactone) as the soft segment. Mechanical tests confirmed the synthesized PEXUU elastomer exhibited excellent elasticity and fatigue resistance that closely mimic the mechanical properties of the natural trachea. The PEXUU elastomers were then processed into porous scaffolds via thermally induced phase separation, exhibited high porosity and favorable hydrophilicity while providing durable XN release kinetic in a sustained manner during degradation. In vitro co‐culture studies demonstrated that the scaffold not only exhibited favorable biocompatibility and supported cartilage regeneration but also effectively downregulated pro‐inflammatory factor expression and promoted the polarization of M1 macrophages toward the M2 phenotype. Furthermore, in vivo experiments revealed that implantation of the PEXUU scaffold significantly alleviated local inflammation and facilitated the formation of mature cartilage tissue. In a rabbit tracheal window defect model, the scaffold markedly reduced granulation tissue formation and preserved luminal patency, ultimately yielding excellent repair outcomes. In conclusion, XN bulk‐modified PEUU represents a dual‐function strategy that combines tailorable mechanical compliance with sustained anti‐inflammatory activity. This approach significantly promotes tracheal regeneration and repair, offering promising prospects for clinical application.
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spelling doaj-art-c4193c8996d24672b1dca0792de0e1d82025-08-20T03:47:41ZengElsevierMaterials Today Bio2590-00642025-06-013210183110.1016/j.mtbio.2025.101831Xanthohumol bulk-modified polyurethane for tracheal repair: A ′killing two birds with one stone' strategy for tailorable mechanics and durable anti-inflammatory efficacySiqiang Zheng0Li Xu1Qitao Bo2Erji Gao3Enkuo Zheng4Lei Xie5Bin Zhao6Jiaoyu Yi7Yang Li8Yong Xu9Yao Wang10Bo Tao11Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, ChinaThe Second Hospital of Ningbo, Ningbo, 315010, ChinaDepartment of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, ChinaDepartment of Pulmonary Nodule Center, Shandong Public Health Clinical Center, Jinan, 250100, ChinaDepartment of Plastic Surgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200127, ChinaShibei Hospital, Jing'an District, Shanghai, 201209, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, China; Corresponding author.Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, China; Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; Corresponding author. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, China.Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, China; Corresponding author.Restoring tracheal defects remains a significant challenge in tissue engineering and regenerative medicine. Current scaffolds fall short of achieving optimal tracheal repair due to unmatched mechanical properties and limited anti‐inflammatory properties. In this study, we incorporated the natural plant‐derived anti-inflammatory molecule Xanthohumol (XN) into the backbone of a degradable polyurethane (PEUU) to create a porous PEXUU scaffold with tailorable mechanical properties and sustained anti‐inflammatory activity. Materials Studio software was initially employed to simulate the feasibility of synthesizing the PEXUU elastomer using XN as a chain extender and poly(ε‐caprolactone) as the soft segment. Mechanical tests confirmed the synthesized PEXUU elastomer exhibited excellent elasticity and fatigue resistance that closely mimic the mechanical properties of the natural trachea. The PEXUU elastomers were then processed into porous scaffolds via thermally induced phase separation, exhibited high porosity and favorable hydrophilicity while providing durable XN release kinetic in a sustained manner during degradation. In vitro co‐culture studies demonstrated that the scaffold not only exhibited favorable biocompatibility and supported cartilage regeneration but also effectively downregulated pro‐inflammatory factor expression and promoted the polarization of M1 macrophages toward the M2 phenotype. Furthermore, in vivo experiments revealed that implantation of the PEXUU scaffold significantly alleviated local inflammation and facilitated the formation of mature cartilage tissue. In a rabbit tracheal window defect model, the scaffold markedly reduced granulation tissue formation and preserved luminal patency, ultimately yielding excellent repair outcomes. In conclusion, XN bulk‐modified PEUU represents a dual‐function strategy that combines tailorable mechanical compliance with sustained anti‐inflammatory activity. This approach significantly promotes tracheal regeneration and repair, offering promising prospects for clinical application.http://www.sciencedirect.com/science/article/pii/S2590006425003916Bulk modificationMechanical complianceLong-lasting effectXanthohumolTracheal repair
spellingShingle Siqiang Zheng
Li Xu
Qitao Bo
Erji Gao
Enkuo Zheng
Lei Xie
Bin Zhao
Jiaoyu Yi
Yang Li
Yong Xu
Yao Wang
Bo Tao
Xanthohumol bulk-modified polyurethane for tracheal repair: A ′killing two birds with one stone' strategy for tailorable mechanics and durable anti-inflammatory efficacy
Materials Today Bio
Bulk modification
Mechanical compliance
Long-lasting effect
Xanthohumol
Tracheal repair
title Xanthohumol bulk-modified polyurethane for tracheal repair: A ′killing two birds with one stone' strategy for tailorable mechanics and durable anti-inflammatory efficacy
title_full Xanthohumol bulk-modified polyurethane for tracheal repair: A ′killing two birds with one stone' strategy for tailorable mechanics and durable anti-inflammatory efficacy
title_fullStr Xanthohumol bulk-modified polyurethane for tracheal repair: A ′killing two birds with one stone' strategy for tailorable mechanics and durable anti-inflammatory efficacy
title_full_unstemmed Xanthohumol bulk-modified polyurethane for tracheal repair: A ′killing two birds with one stone' strategy for tailorable mechanics and durable anti-inflammatory efficacy
title_short Xanthohumol bulk-modified polyurethane for tracheal repair: A ′killing two birds with one stone' strategy for tailorable mechanics and durable anti-inflammatory efficacy
title_sort xanthohumol bulk modified polyurethane for tracheal repair a killing two birds with one stone strategy for tailorable mechanics and durable anti inflammatory efficacy
topic Bulk modification
Mechanical compliance
Long-lasting effect
Xanthohumol
Tracheal repair
url http://www.sciencedirect.com/science/article/pii/S2590006425003916
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