Multifunctional Bioactive Scaffold Facilitating BMSCs-Driven Osteogenesis and Vascularization in Critical-Sized Bone...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Critical-sized bone defects (CSDs) present significant challenges in bone regeneration due to limited mechanical support, poor osteogenic induction, and impaired angiogenesis.
• Existing treatments often fail to address these interconnected barriers, hindering effective bone repair.

Purpose of the Study:

• To develop and evaluate a dual-network bioactive scaffold (bFGF@CB-gel) for synergistic bone regeneration in critical-sized defects.
• To investigate the scaffold's ability to provide mechanical support, deliver bone marrow mesenchymal stem cells (BMSCs), and promote osteogenesis and angiogenesis.

Main Methods:

• Fabrication of a photocurable chondroitin sulfate methacryloyl/bacterial cellulose gel (CB-gel) scaffold incorporating a bio-nano carrier for sustained bFGF release.
• In vitro assessment of BMSC adhesion, proliferation, osteogenic differentiation, and endothelial cell migration/angiogenesis.
• In vivo evaluation of the bFGF@CB-gel scaffold in a rat CSD model using micro-CT and immunohistochemical staining.

Main Results:

• The bFGF@CB-gel scaffold demonstrated sustained bFGF release, enhancing BMSC adhesion, proliferation, and osteogenic differentiation via specific molecular pathways (EGFL/Itga2b, COMP/PI3K/AKT).
• Released bFGF promoted endothelial cell migration and angiogenesis by activating the FGFR/PI3K/AKT/eNOS pathway.
• In vivo studies showed a statistically significant increase in new bone volume and enhanced vascular density in the CSD rat model treated with bFGF@CB-gel.

Conclusions:

• The bFGF@CB-gel scaffold represents a synergistic design for bone regeneration, effectively addressing mechanical, osteogenic, and angiogenic challenges in critical-sized bone defects.
• This dual-network bioactive scaffold shows significant potential as an advanced local delivery system for BMSCs in reconstructive surgery.