IL-4-loaded nanofiber membrane promotes bone regeneration via modulating the immune microenvironment
TL;DR
It is demonstrated 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.
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.