Growth Factor-Free Engineered Biphasic Scaffold for Enhanced Bone Regeneration.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Surgery

Background:

• Large-area bone regeneration is challenging due to incomplete mineralization of current grafts.
• Existing bone grafts often fail to regenerate the entire defect, particularly in the core.

Purpose of the Study:

• To introduce a biphasic, biomimetic scaffold for uniform bone regeneration in large defects.
• To combine structural support with enhanced bioactivity for improved osteogenesis and mineralization.

Main Methods:

• Fabrication of a biphasic scaffold with a porous outer tube and a nanofiber core enriched with decellularized extracellular matrix (dECM).
• Screening of 25 dECMs derived from co-cultures of osteoblasts, chondrocytes, mesenchymal stromal cells, fibroblasts, and endothelial cells.
• Optimization of nanofiber core properties and evaluation of scaffold porosity and mechanical strength.
• In vivo testing in a 10 mm critical-sized femoral defect in rats, assessing bone healing via imaging and histology.

Main Results:

• Osteoblast + Mesenchymal Stromal Cell (OB+MSC)-derived dECM demonstrated the highest osteogenic potential.
• The optimized scaffold exhibited suitable porosity (89.6%) and compressive modulus (123 MPa).
• Scaffolds with CaP and OB+MSC dECM significantly enhanced bone healing, showing a twofold increase in bone volume, mineral density, and cortical bone formation.
• Regenerated bone exhibited a threefold higher compressive modulus than controls and autografts, achieving complete defect bridging by 12 weeks.

Conclusions:

• The biphasic scaffold design effectively promotes uniform bone regeneration in large defects.
• Integrating osteoinductive dECM with structural support offers a promising strategy for clinical translation in bone repair.
• This biomimetic approach overcomes limitations of current bone grafts, enabling complete structural and functional recovery.