Matrix stiffening by self-mineralizable guided bone regeneration

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Collagen membranes are used for guided bone regeneration (GBR), but often lack sufficient strength and osteoinductivity.
• Existing GBR membranes can be brittle and difficult to handle clinically.
• Intrafibrillar mineralization can improve membrane properties but poses challenges for clinical application.

Purpose of the Study:

• To develop a self-mineralizing GBR membrane with improved mechanical properties and osteoinductive potential.
• To investigate the in situ mineralization process and its effect on membrane stiffness.
• To evaluate the capacity of the modified membrane to promote bone regeneration and understand the underlying cellular mechanisms.

Main Methods:

• Covalently conjugating high-molecular weight polyacrylic acid (HPAA) onto Bio-Gide® membranes (BG) to create self-mineralizable HBG membranes.
• Assessing HBG mineralization and stiffness changes in vitro (supersaturated calcium phosphate solution, osteogenic medium) and in vivo (murine calvarial defect).
• Investigating the effect of HBG on mesenchymal stromal cell (MSC) osteogenic differentiation and the Hippo-YAP/TAZ signaling pathway.

Main Results:

• HBG membranes exhibited progressive intrafibrillar mineralization and increased stiffness in various conditions.
• Implanted HBG membranes promoted in situ bone regeneration by stimulating MSC osteogenic differentiation.
• Self-mineralization of HBG inactivated the Hippo-YAP/TAZ signaling cascade in MSCs, promoting osteogenesis.

Conclusions:

• The developed HBG membrane can self-mineralize in situ via intrafibrillar mineralization, enhancing mechanical properties.
• Increased extracellular matrix stiffness in HBG expedites in situ bone regeneration.
• Inactivation of the Hippo-YAP/TAZ signaling pathway by HBG is a key mechanism for enhanced osteogenic differentiation and bone healing.