Effect of hydrostatic pressure on bone regeneration using human mesenchymal stem cells

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Mechanobiology

Background:

• Mechanics is a critical factor in bone tissue engineering.
• Bioprocessors can simulate in vivo mechanics for 3D bone construct generation.
• The effect of hydrostatic pressure (HP) on human mesenchymal stem cells (hMSCs) in bioprocessors is not well understood.

Purpose of the Study:

• To investigate the impact of cyclic hydrostatic pressure (HP) on hMSC behavior within hydroxyapatite scaffolds.
• To compare HP-treated scaffolds with those under atmospheric pressure (AP).

Main Methods:

• hMSCs were cultured and seeded onto hydroxyapatite scaffolds.
• Scaffolds were incubated for 3 weeks under cyclic HP or AP in osteogenic medium.
• Histological, immunohistochemical, and gene expression analyses were performed at multiple time points.

Main Results:

• HP promoted even cell distribution throughout scaffolds, unlike AP where cells remained on the surface.
• HP significantly increased the expression of osteogenic markers (osteocalcin, osteopontin, osteonectin, collagen type 1).
• HP enhanced the expression of key genes for osteogenesis (e.g., Cbfa1, alkaline phosphatase) and integrin β5, while reducing proliferating cell nuclear antigen levels.

Conclusions:

• Cyclic HP in bioprocessors enhances cellular viability and osteogenic differentiation of hMSCs in HA scaffolds.
• HP may slightly decrease MSC proliferation and self-renewal, but no negative effects on bone regeneration were observed.
• Integrin β5, upregulated by HP, may play a role in HP-driven osteogenesis by enhancing migration and differentiation.