From binary bottlenecks to ternary synergy: precise ionic microenvironment regulation in PCL-based electrospun...

Polycaprolactone (PCL) electrospun scaffolds are widely investigated for bone tissue engineering because they mimic the fibrous architecture of the extracellular matrix. However, pristine PCL exhibits insufficient bioactivity and a degradation rate poorly matched to bone regeneration. Binary composites, including PCL/bioactive glass and PCL/tantalum scaffolds, have been developed to address these limitations but face two common bottlenecks. The first is a "loading paradox": excessive nanofiller incorporation causes aggregation, poor interfacial compatibility, and mechanical deterioration. The second is a "signaling gap": limited, predominantly static, or poorly coordinated cues cannot meet the changing biological demands of bone repair. This review examines the rationale and research progress behind the transition from binary modification to ternary synergistic strategies. Introducing a third functional component may improve filler dispersion, enable functional enhancement at lower individual loading levels, and integrate complementary biological signals. In particular, coordinated multi-ion delivery may reproduce aspects of the native bone "ionic cocktail," supporting osteogenesis, angiogenesis, and immune microenvironment regulation. Nevertheless, ternary systems still lack systematic criteria for selecting compatible components and face difficulties in matching ion release and scaffold degradation to the stages of bone regeneration. Future directions include AI-assisted rational design, 4D-printed responsive materials, precise spatiotemporal ion delivery, and personalized manufacturing. Together, these strategies may advance PCL-based scaffolds from broad synergistic enhancement toward precise ionic microenvironment regulation for complex bone defects.