Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration

Abstract Hydrogels are extensively utilized in stem cell-based tissue regeneration, providing a supportive environment that facilitates cell survival, differentiation, and integration with surrounding tissues. However, designing hydrogels for regenerating hard tissues like bone presents significant...

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Main Authors: Bin Xue, Zhengyu Xu, Lan Li, Kaiqiang Guo, Jing Mi, Haipeng Wu, Yiran Li, Chunmei Xie, Jing Jin, Juan Xu, Chunping Jiang, Xiaosong Gu, Meng Qin, Qing Jiang, Yi Cao, Wei Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59016-6
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author Bin Xue
Zhengyu Xu
Lan Li
Kaiqiang Guo
Jing Mi
Haipeng Wu
Yiran Li
Chunmei Xie
Jing Jin
Juan Xu
Chunping Jiang
Xiaosong Gu
Meng Qin
Qing Jiang
Yi Cao
Wei Wang
author_facet Bin Xue
Zhengyu Xu
Lan Li
Kaiqiang Guo
Jing Mi
Haipeng Wu
Yiran Li
Chunmei Xie
Jing Jin
Juan Xu
Chunping Jiang
Xiaosong Gu
Meng Qin
Qing Jiang
Yi Cao
Wei Wang
author_sort Bin Xue
collection DOAJ
description Abstract Hydrogels are extensively utilized in stem cell-based tissue regeneration, providing a supportive environment that facilitates cell survival, differentiation, and integration with surrounding tissues. However, designing hydrogels for regenerating hard tissues like bone presents significant challenges. Here, we introduce macroporous hydrogels with spatiotemporally programmed mechanical properties for stem cell-driven bone regeneration. Using liquid-liquid phase separation and interfacial supramolecular self-assembly of protein fibres, the macroporous structure of hydrogels provide ample space to prevent contact inhibition during proliferation. The rigid protein fibre-coated pore shell provides sustained mechanical cues for guiding osteodifferentiation and protecting against mechanical loads. Temporally, the hydrogel exhibits tunable degradation rates that can synchronize with new tissue deposition to some extent. By integrating localized mechanical heterogeneity, macroporous structures, surface chemistry, and regenerative degradability, we demonstrate the efficacy of these stem cell-encapsulated hydrogels in rabbit and porcine models. This marks a substantial advancement in tailoring the mechanical properties of hydrogels for stem cell-assisted tissue regeneration.
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issn 2041-1723
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publisher Nature Portfolio
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series Nature Communications
spelling doaj-art-1d4e056005874c82933dd3fd813ed0e82025-08-20T02:17:56ZengNature PortfolioNature Communications2041-17232025-04-0116111810.1038/s41467-025-59016-6Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regenerationBin Xue0Zhengyu Xu1Lan Li2Kaiqiang Guo3Jing Mi4Haipeng Wu5Yiran Li6Chunmei Xie7Jing Jin8Juan Xu9Chunping Jiang10Xiaosong Gu11Meng Qin12Qing Jiang13Yi Cao14Wei Wang15Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing UniversityCollaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolCollaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolCollaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing UniversityCollaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolJinan Microecological Biomedicine Shandong LaboratoryJinan Microecological Biomedicine Shandong LaboratoryCollaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolCollaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing UniversityCollaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing UniversityAbstract Hydrogels are extensively utilized in stem cell-based tissue regeneration, providing a supportive environment that facilitates cell survival, differentiation, and integration with surrounding tissues. However, designing hydrogels for regenerating hard tissues like bone presents significant challenges. Here, we introduce macroporous hydrogels with spatiotemporally programmed mechanical properties for stem cell-driven bone regeneration. Using liquid-liquid phase separation and interfacial supramolecular self-assembly of protein fibres, the macroporous structure of hydrogels provide ample space to prevent contact inhibition during proliferation. The rigid protein fibre-coated pore shell provides sustained mechanical cues for guiding osteodifferentiation and protecting against mechanical loads. Temporally, the hydrogel exhibits tunable degradation rates that can synchronize with new tissue deposition to some extent. By integrating localized mechanical heterogeneity, macroporous structures, surface chemistry, and regenerative degradability, we demonstrate the efficacy of these stem cell-encapsulated hydrogels in rabbit and porcine models. This marks a substantial advancement in tailoring the mechanical properties of hydrogels for stem cell-assisted tissue regeneration.https://doi.org/10.1038/s41467-025-59016-6
spellingShingle Bin Xue
Zhengyu Xu
Lan Li
Kaiqiang Guo
Jing Mi
Haipeng Wu
Yiran Li
Chunmei Xie
Jing Jin
Juan Xu
Chunping Jiang
Xiaosong Gu
Meng Qin
Qing Jiang
Yi Cao
Wei Wang
Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration
Nature Communications
title Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration
title_full Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration
title_fullStr Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration
title_full_unstemmed Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration
title_short Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration
title_sort hydrogels with programmed spatiotemporal mechanical cues for stem cell assisted bone regeneration
url https://doi.org/10.1038/s41467-025-59016-6
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