Microtopography-induced changes in cell nucleus morphology enhance bone regeneration by modulating the cellular secretome

Xinlong Wang, Yiming Li, Zitong Lin, Indira Pla, Raju Gajjela, Basil Baby Mattamana, Maya Joshi, Yugang Liu, Huifeng Wang, Amy B. Zun, Hao Wang, Ching-Man Wai, Vasundhara Agrawal, Cody L. Dunton, Chongwen Duan, Bin Jiang, Vadim Backman, Tong-Chuan He, Russell R. Reid, Yuan Luo and Guillermo A. Ameer ()
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Xinlong Wang: Northwestern University
Yiming Li: Northwestern University Feinberg School of Medicine
Zitong Lin: Northwestern University Feinberg School of Medicine
Indira Pla: Northwestern University
Raju Gajjela: Northwestern University
Basil Baby Mattamana: Northwestern University
Maya Joshi: Northwestern University
Yugang Liu: Northwestern University
Huifeng Wang: Northwestern University
Amy B. Zun: Northwestern University
Hao Wang: The University of Chicago Medical Center
Ching-Man Wai: Northwestern University Feinberg School of Medicine
Vasundhara Agrawal: Northwestern University
Cody L. Dunton: Northwestern University
Chongwen Duan: Northwestern University
Bin Jiang: Northwestern University
Vadim Backman: Northwestern University
Tong-Chuan He: Northwestern University
Russell R. Reid: Northwestern University
Yuan Luo: Northwestern University
Guillermo A. Ameer: Northwestern University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Nuclear morphology plays a critical role in regulating gene expression and cell functions. While most research has focused on the direct effects of nuclear morphology on cell fate, its impact on the cell secretome and surrounding cells remains largely unexplored. In this study, we fabricate implants with a micropillar topography using methacrylated poly(octamethylene citrate)/hydroxyapatite (mPOC/HA) composites to investigate how micropillar-induced nuclear deformation influences cell secretome for osteogenesis and cranial bone regeneration. In vitro, cells with deformed nuclei show enhanced secretion of proteins that support extracellular matrix (ECM) organization, which promotes osteogenic differentiation in neighboring mesenchymal stromal cells (MSCs). In a female mouse model with critical-size cranial defects, nuclear-deformed MSCs on micropillar mPOC/HA implants elevate Col1a2 expression, contributing to bone matrix formation, and drive cell differentiation toward osteogenic progenitor cells. These findings indicate that micropillars modulate the secretome of hMSCs, thereby influencing the fate of surrounding cells through matricrine effects.

Date: 2025
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DOI: 10.1038/s41467-025-60760-y

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