Chromatin reprogramming and bone regeneration in vitro and in vivo via the microtopography-induced constriction of cell nuclei

Xinlong Wang, Vasundhara Agrawal, Cody L. Dunton, Yugang Liu, Ranya K.A. Virk, Priyam A. Patel, Lucas Carter, Emily M. Pujadas, Yue Li, Surbhi Jain, Hao Wang, Na Ni, Hsiu Ming Tsai, Nancy Rivera-Bolanos, Jane Frederick, Eric Roth, Reiner Bleher, Chongwen Duan, Panagiotis Ntziachristos, Tong Chuan HeRussell R. Reid, Bin Jiang, Hariharan Subramanian, Vadim Backman*, Guillermo A. Ameer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Topographical cues on cells can, through contact guidance, alter cellular plasticity and accelerate the regeneration of cultured tissue. Here we show how changes in the nuclear and cellular morphologies of human mesenchymal stromal cells induced by micropillar patterns via contact guidance influence the conformation of the cells’ chromatin and their osteogenic differentiation in vitro and in vivo. The micropillars impacted nuclear architecture, lamin A/C multimerization and 3D chromatin conformation, and the ensuing transcriptional reprogramming enhanced the cells’ responsiveness to osteogenic differentiation factors and decreased their plasticity and off-target differentiation. In mice with critical-size cranial defects, implants with micropillar patterns inducing nuclear constriction altered the cells’ chromatin conformation and enhanced bone regeneration without the need for exogenous signalling molecules. Our findings suggest that medical device topographies could be designed to facilitate bone regeneration via chromatin reprogramming.

Original languageEnglish (US)
Pages (from-to)1514-1529
Number of pages16
JournalNature Biomedical Engineering
Volume7
Issue number11
DOIs
StatePublished - Nov 2023

ASJC Scopus subject areas

  • Bioengineering
  • Biotechnology
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Computer Science Applications

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