In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment

Abstract Blood clots (BCs) play a crucial biomechanical role in promoting osteogenesis and regulating mesenchymal stem cell (MSC) function and fate. This study shows that BC formation enhances MSC osteogenesis by activating Itgb1/Fak-mediated focal adhesion and subsequent Runx2-mediated bone regener...

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Main Authors: Wangxiao He, Fan Ding, Liqiang Zhang, Wenjia Liu
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56513-6
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author Wangxiao He
Fan Ding
Liqiang Zhang
Wenjia Liu
author_facet Wangxiao He
Fan Ding
Liqiang Zhang
Wenjia Liu
author_sort Wangxiao He
collection DOAJ
description Abstract Blood clots (BCs) play a crucial biomechanical role in promoting osteogenesis and regulating mesenchymal stem cell (MSC) function and fate. This study shows that BC formation enhances MSC osteogenesis by activating Itgb1/Fak-mediated focal adhesion and subsequent Runx2-mediated bone regeneration. Notably, BC viscoelasticity regulates this effect by modulating Runx2 nuclear translocation. To mimic this property, a viscoelastic peptide bionic hydrogel named BCgel was developed, featuring a nanofiber network, Itgb1 binding affinity, BC-like viscoelasticity, and biosafety. The anticipated efficacy of BCgel is demonstrated by its ability to induce nuclear translocation of Runx2 and promote bone regeneration in both in vitro experiments and in vivo bone defect models with blood clot defect, conducted on rats as well as beagles. This study offers insights into the mechano-transduction mechanisms of MSCs during osteogenesis and presents potential guidelines for the design of viscoelastic hydrogels in bone regenerative medicine.
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institution Kabale University
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spelling doaj-art-08390d18407d43acbfce8a261ac313092025-02-02T12:32:51ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-56513-6In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironmentWangxiao He0Fan Ding1Liqiang Zhang2Wenjia Liu3Department of Stomatology, Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Stomatology, Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Stomatology, Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong UniversityInstitute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Blood clots (BCs) play a crucial biomechanical role in promoting osteogenesis and regulating mesenchymal stem cell (MSC) function and fate. This study shows that BC formation enhances MSC osteogenesis by activating Itgb1/Fak-mediated focal adhesion and subsequent Runx2-mediated bone regeneration. Notably, BC viscoelasticity regulates this effect by modulating Runx2 nuclear translocation. To mimic this property, a viscoelastic peptide bionic hydrogel named BCgel was developed, featuring a nanofiber network, Itgb1 binding affinity, BC-like viscoelasticity, and biosafety. The anticipated efficacy of BCgel is demonstrated by its ability to induce nuclear translocation of Runx2 and promote bone regeneration in both in vitro experiments and in vivo bone defect models with blood clot defect, conducted on rats as well as beagles. This study offers insights into the mechano-transduction mechanisms of MSCs during osteogenesis and presents potential guidelines for the design of viscoelastic hydrogels in bone regenerative medicine.https://doi.org/10.1038/s41467-025-56513-6
spellingShingle Wangxiao He
Fan Ding
Liqiang Zhang
Wenjia Liu
In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment
Nature Communications
title In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment
title_full In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment
title_fullStr In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment
title_full_unstemmed In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment
title_short In situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment
title_sort in situ osteogenic activation of mesenchymal stem cells by the blood clot biomimetic mechanical microenvironment
url https://doi.org/10.1038/s41467-025-56513-6
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