hMSCs form Osteocyte-like Cell Networks within Strain-Stiffening Bottlebrush Polymer Hydrogels
Year: 2026
Type: preprint
Abstract: Summary 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 .
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Awards: Laser Scanning Confocal Microscope, Clickable Microgel Scaffolds for MSC Expansion and Delivery, Granular hydrogels for the controlled delivery of immunomodulatory and angiogenic extracellular vesicles to enhance bone tissue regeneration, Interdisciplinary Training in Musculoskeletal Research
OpenAlex ID: W7214069301