Core-Shell Electrospun Membranes Enable Antimicrobial and Immunomodulatory Local Therapy for Periodontitis.

Periodontitis is a chronic inflammatory disease that progressively destroys periodontal tissues and can lead to tooth loss, affecting more than one billion people worldwide. Here, we developed coaxial electrospun core-shell scaffolds designed for local periodontal therapy, comprising a polycaprolactone (PCL) core and a polyvinylpyrrolidone (PVP) shell. Nanohydroxyapatite and lignin-silver nanoparticles (Lig-Ag NPs) were incorporated in the core to support regenerative and antimicrobial functions, while ketoprofen was loaded in the shell for localized anti-inflammatory delivery. The coaxial architecture enabled spatial compartmentalization of bioactive components and produced membranes with ketoprofen encapsulation efficiencies of 79-89.5%. Drug release was burst-dominated and reached a plateau within 48 h, with the 0.75HADL formulation achieving 92% cumulative release within 24 h. This release behavior is attributed to the rapid dissolution of the hydrophilic PVP shell, enabling immediate drug availability at the target site. In vitro testing showed cytocompatibility toward human gingival fibroblasts and immunomodulatory activity in RAW 264.7 macrophages, including marked suppression of MCP-1 and MMP-9 expression. The Lig-Ag NP-functionalized membranes reduced Enterococcus faecalis counts by 2-3 log10 CFU/mL over 48 h and exerted a mycostatic effect against Candida albicans. Together, these results indicate a coordinated biological response, combining cytocompatibility, antimicrobial activity, and controlled immunomodulation. Overall, the 0.75HADL coaxial membrane provided the most favorable balance of physicochemical performance and biological activity, supporting its potential as a local multifunctional scaffold for periodontal applications.