A VEGF/BMP-6-Functionalized PLGA Scaffold Combined with Mesenchymal Stem Cells Promotes Bone Regeneration in a Chicken Femoral Defect Model

Repair of critical-sized bone defects remains challenging because successful regeneration requires both osteogenesis and vascular support. This study investigated whether a biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffold functionalized with vascular endothelial growth factor (VEGF) and bone morphogenetic protein-6 (BMP-6), combined with chicken bone marrow-derived mesenchymal stem cells (MSCs), could enhance bone regeneration. Porous PLGA scaffolds were functionalized with VEGF and BMP-6, seeded with MSCs, and implanted into surgically created chicken femoral defects. Bone regeneration was evaluated after eight weeks by micro-computed tomography (micro-CT) and histological analysis. The effects of VEGF and BMP-6 on MSC osteogenic differentiation were further assessed by Alizarin Red S staining and quantitative real-time PCR. Among the treatment groups, VEGF/BMP-6-functionalized scaffolds combined with MSCs produced the greatest bone volume and most extensive defect bridging. In vitro, VEGF and BMP-6 modulated matrix mineralization and osteogenic marker expression. These findings demonstrate the regenerative potential of a multifunctional PLGA-based construct integrating growth-factor functionalization and MSC transplantation. Because an MSC-only scaffold group was not included, the individual contributions of MSCs and growth-factor functionalization to the enhanced in vivo response cannot be distinguished.