Anisotropic structure of nanofiber hydrogel accelerates diabetic wound healing via triadic synergy of immune-angiogenic-neurogenic microenvironments

Wound healing in chronic diabetic patients remains challenging due to the multiple types of cellular dysfunction and the impairment of multidimensional microenvironments. The physical signals of structural anisotropy offer significant potential for orchestrating multicellular regulation through phys...

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Main Authors: Kunkoo Kim, Jia Yang, Chengli Li, Chun-Yi Yang, Peilun Hu, Yaosai Liu, Yin-yuan Huang, Xiaohan Sun, Ming Chi, Chenyu Huang, Xiaodan Sun, Lingyun Zhao, Xiumei Wang
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/S2452199X25000040
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author Kunkoo Kim
Jia Yang
Chengli Li
Chun-Yi Yang
Peilun Hu
Yaosai Liu
Yin-yuan Huang
Xiaohan Sun
Ming Chi
Chenyu Huang
Xiaodan Sun
Lingyun Zhao
Xiumei Wang
author_facet Kunkoo Kim
Jia Yang
Chengli Li
Chun-Yi Yang
Peilun Hu
Yaosai Liu
Yin-yuan Huang
Xiaohan Sun
Ming Chi
Chenyu Huang
Xiaodan Sun
Lingyun Zhao
Xiumei Wang
author_sort Kunkoo Kim
collection DOAJ
description Wound healing in chronic diabetic patients remains challenging due to the multiple types of cellular dysfunction and the impairment of multidimensional microenvironments. The physical signals of structural anisotropy offer significant potential for orchestrating multicellular regulation through physical contact and cellular mechanosensing pathways, irrespective of cell type. In this study, we developed a highly oriented anisotropic nanofiber hydrogel designed to provide directional guidance for cellular extension and cytoskeletal organization, thereby achieving pronounced multicellular modulation, including shape-induced polarization of macrophages, morphogenetic maturation of Schwann cells, oriented extracellular matrix (ECM) deposition by fibroblasts, and enhanced vascularization by endothelial cells. Additionally, we incorporated a VEGF-mimicking peptide to further reinforce angiogenesis, a pivotal phase that interlocks with immune regulation, neurogenesis, and tissue regeneration, ultimately contributing to optimized inter-microenvironmental crosstalk. In vivo studies validated that the anisotropic bioactive nanofiber hydrogel effectively accelerated diabetic wound healing by harnessing the triadic synergy of the immune-angiogenic-neurogenic microenvironments. Our findings highlight the promising potential of combining physical and bioactive signals for the modulation of various cell types and the refinement of the multidimensional microenvironment, offering a novel strategy for diabetic wound healing.
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institution Kabale University
issn 2452-199X
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publisher KeAi Communications Co., Ltd.
record_format Article
series Bioactive Materials
spelling doaj-art-05a79e7f05914694b7ab9eb6f7b884562025-01-12T05:25:33ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-05-01476482Anisotropic structure of nanofiber hydrogel accelerates diabetic wound healing via triadic synergy of immune-angiogenic-neurogenic microenvironmentsKunkoo Kim0Jia Yang1Chengli Li2Chun-Yi Yang3Peilun Hu4Yaosai Liu5Yin-yuan Huang6Xiaohan Sun7Ming Chi8Chenyu Huang9Xiaodan Sun10Lingyun Zhao11Xiumei Wang12State Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, ChinaState Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, ChinaBeijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, 102218, Beijing, ChinaState Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, China; Center for Biomaterials and Regenerative Medicine, Wuzhen Laboratory, 314500, Tongxiang, China; Corresponding author. State Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, China.Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, 102218, Beijing, China; Beijing Friendship Hospital, Capital Medical University, 102218, Beijing, ChinaBeijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, 102218, Beijing, ChinaState Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, China; Department of Biomedical Engineering, Washington University in St. Louis, 63130, St. Louis, Missouri, United StatesState Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, ChinaState Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, ChinaBeijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, 102218, Beijing, ChinaState Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, ChinaState Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, ChinaState Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, China; Corresponding author.Wound healing in chronic diabetic patients remains challenging due to the multiple types of cellular dysfunction and the impairment of multidimensional microenvironments. The physical signals of structural anisotropy offer significant potential for orchestrating multicellular regulation through physical contact and cellular mechanosensing pathways, irrespective of cell type. In this study, we developed a highly oriented anisotropic nanofiber hydrogel designed to provide directional guidance for cellular extension and cytoskeletal organization, thereby achieving pronounced multicellular modulation, including shape-induced polarization of macrophages, morphogenetic maturation of Schwann cells, oriented extracellular matrix (ECM) deposition by fibroblasts, and enhanced vascularization by endothelial cells. Additionally, we incorporated a VEGF-mimicking peptide to further reinforce angiogenesis, a pivotal phase that interlocks with immune regulation, neurogenesis, and tissue regeneration, ultimately contributing to optimized inter-microenvironmental crosstalk. In vivo studies validated that the anisotropic bioactive nanofiber hydrogel effectively accelerated diabetic wound healing by harnessing the triadic synergy of the immune-angiogenic-neurogenic microenvironments. Our findings highlight the promising potential of combining physical and bioactive signals for the modulation of various cell types and the refinement of the multidimensional microenvironment, offering a novel strategy for diabetic wound healing.http://www.sciencedirect.com/science/article/pii/S2452199X25000040Anisotropic nanofiber hydrogelSelf-assembling peptideMulticellular modulationMultidimensional microenvironment refinementDiabetic wound healing
spellingShingle Kunkoo Kim
Jia Yang
Chengli Li
Chun-Yi Yang
Peilun Hu
Yaosai Liu
Yin-yuan Huang
Xiaohan Sun
Ming Chi
Chenyu Huang
Xiaodan Sun
Lingyun Zhao
Xiumei Wang
Anisotropic structure of nanofiber hydrogel accelerates diabetic wound healing via triadic synergy of immune-angiogenic-neurogenic microenvironments
Bioactive Materials
Anisotropic nanofiber hydrogel
Self-assembling peptide
Multicellular modulation
Multidimensional microenvironment refinement
Diabetic wound healing
title Anisotropic structure of nanofiber hydrogel accelerates diabetic wound healing via triadic synergy of immune-angiogenic-neurogenic microenvironments
title_full Anisotropic structure of nanofiber hydrogel accelerates diabetic wound healing via triadic synergy of immune-angiogenic-neurogenic microenvironments
title_fullStr Anisotropic structure of nanofiber hydrogel accelerates diabetic wound healing via triadic synergy of immune-angiogenic-neurogenic microenvironments
title_full_unstemmed Anisotropic structure of nanofiber hydrogel accelerates diabetic wound healing via triadic synergy of immune-angiogenic-neurogenic microenvironments
title_short Anisotropic structure of nanofiber hydrogel accelerates diabetic wound healing via triadic synergy of immune-angiogenic-neurogenic microenvironments
title_sort anisotropic structure of nanofiber hydrogel accelerates diabetic wound healing via triadic synergy of immune angiogenic neurogenic microenvironments
topic Anisotropic nanofiber hydrogel
Self-assembling peptide
Multicellular modulation
Multidimensional microenvironment refinement
Diabetic wound healing
url http://www.sciencedirect.com/science/article/pii/S2452199X25000040
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