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

Area of Science:

• Biomaterials Science
• Cell Biology
• Regenerative Medicine

Background:

• Nuclear morphology influences gene expression and cell functions.
• The impact of nuclear morphology on cell secretome and paracrine signaling is understudied.
• Osteogenesis and cranial bone regeneration are critical clinical challenges.

Purpose of the Study:

• To investigate how micropillar-induced nuclear deformation affects cell secretome for osteogenesis.
• To evaluate the efficacy of mPOC/HA composite implants with micropillar topography for cranial bone regeneration.
• To elucidate the role of nuclear deformation in modulating mesenchymal stromal cell (MSC) secretome and paracrine signaling.

Main Methods:

• Fabrication of implants with micropillar topography using methacrylated poly(octamethylene citrate)/hydroxyapatite (mPOC/HA) composites.
• In vitro assessment of protein secretion from cells with deformed nuclei.
• In vivo study using a female mouse model with critical-size cranial defects.
• Analysis of gene expression (Col1a2) and cell differentiation markers.

Main Results:

• Micropillar-induced nuclear deformation enhanced secretion of extracellular matrix (ECM)-organizing proteins.
• Deformed nuclei promoted osteogenic differentiation in neighboring mesenchymal stromal cells (MSCs) in vitro.
• In vivo, nuclear-deformed MSCs on micropillar implants increased Col1a2 expression and bone matrix formation.
• Nuclear deformation drove MSC differentiation toward osteogenic progenitor cells in a cranial defect model.

Conclusions:

• Micropillars on mPOC/HA implants effectively induce nuclear deformation in MSCs.
• Modulated MSC secretome via nuclear deformation promotes osteogenesis and cranial bone regeneration.
• This study highlights matricrine signaling as a mechanism by which nuclear morphology influences tissue regeneration.