Whitlockite-loaded silk fibroin/polyvinyl alcohol hydrogel composited with porous tantalum scaffold enhances bone regeneration and immunomodulation via the TGF-β/NRROS signaling pathway

Bone defects, caused by diseases or trauma, significantly impact patients' quality of life. While porous Tantalum (pTa) scaffolds have shown promise in bone defect repair due to their excellent properties, their bioinert nature cannot meet the bioactive stimulation required for bone regeneration. To address these challenges, this study designed a composite scaffold composed of a 3D-printed pTa scaffold and a silk fibroin-crosslinked polyvinyl alcohol (SP) hydrogel loaded with whitlockite (WH). WH, a secondary inorganic component of bone tissue, was incorporated into the hydrogel to enhance its osteogenic, angiogenic and anti-inflammatory properties. The optimal proportions of PVA and WH were determined through extensive experiments. The resulting scaffold, designated as SP-pTa@WH, demonstrated remarkable biocompatibility and effectively promoted bone tissue repair in vitro and in vivo. Mechanistic studies revealed that SP-pTa@WH significantly modulated macrophage polarization towards the M2 phenotype and upregulated the expression of key osteogenic genes. High-throughput gene sequencing analysis further identified the TGF-β signaling pathway, particularly the NRROS gene, as critical in mediating the anti-inflammatory effects of SP-pTa@WH. Overall, this study provides a novel composite scaffold with enhanced osteogenic and immunomodulatory capabilities, offering broad prospects for clinical applications in bone defect repair.