Electrospun Tri‐Layer Core‐Sheath Nanofibrous Coating for Sequential Treatment of Postoperative Complications in Orthopedic Implants

The growing global prevalence of orthopedic conditions associated with an aging population has significantly increased the clinical demand for orthopedic implants. However, postoperative complications, including postoperative bleeding, implant associated infections (IAIs), and inadequate osteogenesis, continue to limit surgical outcomes. To simultaneously mitigate these challenges, a multifunctional electrospun fibrous coating (EFC) is developed, with an inner tri-layer core-sheath nanostructure to separately load tranexamic acid (TXA), fenoprofen (Fen), and puerarin (Pue) in the shell, middle, and core sections, respectively. Using poly(ε-caprolactone) (PCL) and polyvinylpyrrolidone (PVP) as polymeric matrices, tri-layer electrospun fibers are successfully fabricated, that spatially compartmentalize TXA, Fen, and Pue despite technical challenges. In vitro and in vivo studies demonstrated that TXA rapidly exerted hemostatic effects, effectively reducing initial postoperative bleeding. Subsequently, Fen suppressed the virulence of Staphylococcus aureus (S. aureus) by inhibiting the SaeRS two-component system, disrupting the biofilm barrier, and accelerating bacterial clearance by the host. Finally, Pue drove macrophage M2 polarization, which promoted angiogenesis and osteogenesis, ultimately supporting bone regeneration and long-term implant integration. EFC offers a promising sequential therapeutic strategy to address postoperative complications of orthopedic implant surgery. The protocol reported here exhibits a new way for developing novel medicated nanomaterials based on the distinct process-structure-performance relationship.