Structurally optimized electrospun scaffold for biomaterial-controlled synergistic enhancement of defective bone healing

Bone repair processes are tightly affected by fiber topographies of scaffolds and can be promoted by coupling with chemotactic and/or angiogenic molecules. Here, we developed polycaprolactone (PCL) and collagen-based fibrous scaffolds expressing various architectures via a modified electrospinning set up. We conjugated the as-spun scaffolds with caffeic acid (CA) and/or a cartilage oligomeric matrix protein of angiopoietin 1 (COMP-Ang1). The CA-coupled PCL/collagen scaffold (PCL/col/CA) exhibited greater treatment efficacies for biomimetic and cellular mineralization, expression of osteogenic and chemotactic molecules, and cell migration than did the PCL/col treatment alone. Among the PCL/col/CA scaffolds, the radially symmetric grid-patterned scaffold (rG-PCL/col/CA) showed the greatest bioactivities. The linking of the rG-PCL/col/CA with COMP-Ang1 increased the expression of vascular endothelial growth factor by cells. The COMP-Ang1-linked rG-PCL/col/CA formed more new blood vessels and expressed more chemotactic molecules in a rat model of femoral defects than did the scaffold alone. Compared with PCL/col/CA scaffolds, the COMP-Ang1-coupled rG-PCL/col/CA scaffold stimulated faster and greater healing of femoral defects. Collectively, this study demonstrates that the coupling of a radially grid-patterned fibrous scaffold with CA and COMP-Ang1 greatly enhances scaffold-mediated bone healing via synergistic improvements in vascularization, cell migration, and formation and maturation of new bones in defected regions.