hMSCs for Osteocyte-like Cell Networks within Strain-Stiffening Bottlebrush Polymer Hydrogels
- 1University of Wisconsin - Madison
Abstract
Bone formation and remodeling depend on dynamic biochemical and biomechanical signaling from the collagen-rich osteoid that precedes mineralization, yet the role of osteoid nonlinear mechanics in regulating osteocyte-like network formation remains poorly understood. Here, we engineered a synthetic bottlebrush polymer hydrogel (BB) that mimics key mechanical features of osteoid and compared it to collagen type-I (Col1) matrices with matched shear modulus (~70 Pa) and strain-stiffening behavior. Human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) were cultured for 28 days in growth (GM) or osteogenic media (OM) to examine network formation, and functional connectivity using live cell fluorescence recovery after photobleaching. hMSCs cultured in BB networks and OM showed upregulation of early osteocyte markers compared to Col1. We find that strain-stiffening materials with minimal stress relaxation promote osteocyte-like cell differentiation with functional connectivity, establishing osteoid-mimetic BB hydrogels as a promising matrix to study human osteocytogenesis and osteocyte mechanotransduction in vitro.
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BibTeX
@misc{ohnsorg2026hmscs,
title = {{hMSCs for Osteocyte-like Cell Networks within Strain-Stiffening Bottlebrush Polymer Hydrogels}},
author = {M. L. Ohnsorg and N. E. Friend and S. E. Givens and D. Saeb and K. M. Mash and K. S. Anseth},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.753603},
url = {https://www.biorxiv.org/content/10.64898/2026.09.22.753603v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - hMSCs for Osteocyte-like Cell Networks within Strain-Stiffening Bottlebrush Polymer Hydrogels
AU - M. L. Ohnsorg
AU - N. E. Friend
AU - S. E. Givens
AU - D. Saeb
AU - K. M. Mash
AU - K. S. Anseth
PY - 2026
DA - 2026/09/22
PB - bioRxiv
DO - 10.64898/2026.09.22.753603
UR - https://www.biorxiv.org/content/10.64898/2026.09.22.753603v1
AB - Bone formation and remodeling depend on dynamic biochemical and biomechanical signaling from the collagen-rich osteoid that precedes mineralization, yet the role of osteoid nonlinear mechanics in regulating osteocyte-like network formation remains poorly understood. Here, we engineered a synthetic bottlebrush polymer hydrogel (BB) that mimics key mechanical features of osteoid and compared it to collagen type-I (Col1) matrices with matched shear modulus (~70 Pa) and strain-stiffening behavior. Human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) were cultured for 28 days in growth (GM) or osteogenic media (OM) to examine network formation, and functional connectivity using live cell fluorescence recovery after photobleaching. hMSCs cultured in BB networks and OM showed upregulation of early osteocyte markers compared to Col1. We find that strain-stiffening materials with minimal stress relaxation promote osteocyte-like cell differentiation with functional connectivity, establishing osteoid-mimetic BB hydrogels as a promising matrix to study human osteocytogenesis and osteocyte mechanotransduction in vitro.
ER -