Janus-structured piezoelectric membrane couples barrier protection with pathological microenvironment-responsive bioactivity for periodontal bone regeneration

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 Zn 2+ 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.