Janus-structured piezoelectric membrane couples barrier protection with pathological microenvironment-responsive...

Periodontal bone regeneration remains challenging due to the persistent infection-inflammation-bone resorption cycle and the rapid invasion of epithelial and gingival connective tissues into defect sites. Here, we developed a biodegradable Janus membrane (J-PLLA-ZnO) based on poly(L-lactic acid) (PLLA) that spatially integrates barrier protection and pH-responsive bioactivity within a single construct. A dense PLLA layer facing soft tissues prevents premature tissue infiltration and maintains regenerative space, while a porous defect-facing interface functionalized with ZnO nanowires provides bioactive regulation. The ZnO nanowires enhance the overall piezoelectric response of the membrane and enable pH-responsive Zn²⁺ release under the acidic periodontal microenvironment, thereby delivering antibacterial, immunomodulatory, and osteogenic cues. In a rat periodontitis model, J-PLLA-ZnO rapidly suppressed infection-associated inflammation. One week after implantation, peripheral neutrophil percentage decreased to approximately 21% of those in the J-PLLA group, accompanied by reduced tumor necrosis factor-α expression and increased cluster of differentiation 206 expression, consistent with a shift toward a reparative macrophage phenotype. At week 6, J-PLLA-ZnO increased the osteocalcin-positive bone-forming area by approximately 1.5-fold compared with non-Janus PLLA-ZnO, indicating improved periodontal bone regeneration. Moreover, the cementoenamel junction-alveolar bone crest distance was reduced by approximately 40% relative to untreated controls. Meanwhile, the membrane underwent gradual biodegradation throughout the healing process. These findings demonstrate that integrating spatial barrier function with pH-responsive bioactivity represents a promising strategy for guided tissue regeneration in inflammatory periodontal defects.