Flowerbed-Inspired Mg-Loaded Scaffold Accelerates Critical-Sized Bone-Defect Repair by Reprogramming the...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Engineering

Background:

• Critical-sized bone defects present significant challenges due to limited self-healing.
• Existing treatments often struggle with central defect regeneration and load-bearing capacity.

Purpose of the Study:

• To develop a biomimetic composite scaffold for repairing critical-sized bone defects.
• To create a simulated osteogenic niche that promotes bone regeneration in load-bearing areas.

Main Methods:

• Fabrication of a composite scaffold integrating a magnesium-ion-loaded alginate hydrogel (PR/AlgMA/Mg) within a triply periodic minimal surface (TPMS) porous Ti6Al4V framework.
• In vitro assessment of hydrogel properties, Mg2+ release, and osteogenic differentiation of mesenchymal stem cells (MSCs).
• In vivo evaluation in rat calvarial and beagle femoral condyle defect models, including single-cell RNA sequencing analysis.

Main Results:

• The PR/AlgMA/Mg hydrogel demonstrated controlled Mg2+ release and supported MSC osteogenic differentiation.
• The composite scaffold significantly enhanced bone bridging in critical-sized calvarial defects.
• Single-cell sequencing revealed a CCN3+ MSC subpopulation crucial for osteogenesis and immune modulation (M2 macrophage polarization) via PTN.
• The TPMS framework ensured uniform stress distribution and facilitated cell infiltration.
• In vivo, the scaffold promoted contact osteogenesis and improved biomechanical integration in femoral condyle defects.

Conclusions:

• The biomimetic scaffold effectively constructs an osteogenic niche by recruiting progenitor cells and reprogramming the immune microenvironment.
• This strategy shows significant promise for the repair of critical bone defects, particularly in load-bearing applications.
• The combination of hydrogel properties and TPMS architecture offers a synergistic approach to bone regeneration.