IL-4-loaded nanofiber membrane promotes bone regeneration via modulating the immune microenvironment

Abstract

Developing multifunctional scaffolds that combine tailored physical properties with bioactivity is essential for advanced bone tissue engineering. This study fabricated an interleukin-4 (IL-4)-loaded polycaprolactone/gelatin (PCL-Gel) nanofiber membrane via electrospinning. Incorporating Gel significantly refined fiber diameter (978 ± 324 nm, 883 ± 234 nm for PCL), increased surface roughness, and improved hydrophilicity, reducing the water contact angle from 161.3° to 43.3°. IL-4 was successfully encapsulated without altering fiber morphology. The composite membrane exhibited a sustained release profile with a low initial burst (20%–30%) and high cumulative release (>85% over 30 d). In vitro, the PCL/Gel/IL-4 scaffold markedly promoted the osteogenesis of bone marrow mesenchymal stem cells, which was demonstrated by increased alkaline phosphatase activity and enhanced deposition of mineralized nodules. Moreover, it induced a shift in macrophage polarization to the M2 phenotype, accompanied by elevated expression of the anti-inflammatory mediators Arg-1 and IL-10 and downregulating pro-inflammatory genes. These results demonstrate that the PCL/Gel/IL-4 membrane synergistically improves physical properties, release behavior, osteogenic capacity, and immunomodulation, offering a promising multi-functional platform for bone regeneration.