**Background:** Periodontal bone defects from periodontitis, tumor, or trauma remain a major clinical challenge. Guided tissue regeneration (GTR) and guided bone regeneration (GBR) using barrier membranes are key strategies, but traditional membranes lack bioactive capacity to actively regulate bone repair. Metal-phenolic networks (MPNs), formed by coordination of metal ions and phenolic ligands, offer bioactive nanocoatings with anti-inflammatory, angiogenic, and osteogenic potential. This study aimed to develop a Janus porous PLA membrane with a tannic acid (TA)/Cu²⁺ MPN nanointerface for biomimetic periodontal bone regeneration.
**Methods:** Janus porous PLA membranes (PLAM) were fabricated via unidirectional evaporation-induced phase separation with PEG as porogen. MPN coatings were assembled layer-by-layer using TA (0.8 mg/mL) and Cu²⁺ (0.2 mg/mL) solutions, producing PLAM-1, PLAM-5, and PLAM-10 (1, 5, or 10 MPN layers). Membranes were characterized by SEM, UV-vis, FTIR, water contact angle, and mechanical testing. In vitro, hPDLSCs were assessed for viability (Live/Dead, CCK-8), migration (transwell), and osteogenic differentiation (Alizarin Red, qRT-PCR for ALP, Runx2, OPN). BMDMs were evaluated for M1/M2 polarization (flow cytometry, qRT-PCR for iNOS, TNF-α, CD206, Arg-1). HUVECs were tested for angiogenesis (tube formation assay, qRT-PCR for HIF, SCF, VEGF). In vivo, bilateral periodontal bone defects (5×4×1 mm³) were created in Wistar rats (n=72, 24/group) and treated with no treatment (NC), PLAM, or PLAM-10. Micro-CT analysis at 1, 2, 4, and 8 weeks assessed BV/TV, BS/TV, Tb.Th, and Tb.Sp. Immunofluorescence staining at 2 weeks evaluated ALP, Runx2, iNOS, CD206, and CD31 expression.
**Key Results:** PLAM-10 showed significantly reduced water contact angle (56.4°) vs. PLAM-B (89.0°), indicating enhanced hydrophilicity. PLAM-10 significantly increased hPDLSC migration vs. NC and PLAM (p<0.001). In BMDMs, PLAM-MPN significantly reduced M1 polarization (iNOS⁺ cells) and downregulated iNOS and TNF-α mRNA vs. LPS-stimulated controls (p<0.01–0.001). PLAM-10 significantly enhanced HUVEC tube formation (higher node counts, segments, meshes, total tube length) and upregulated HIF, SCF, and VEGF mRNA (p<0.05–0.001). PLAM-10 increased mineralized nodule formation ~3-fold vs. NC and upregulated ALP >5-fold at 7 days, Runx2 at 7–21 days, and OPN at 21 days (p<0.05–0.001). In vivo, PLAM-10 showed significantly higher BV/TV and BS/TV at 1, 2, 4, and 8 weeks vs. NC and PLAM (p<0.05–0.001). Tb.Th was significantly higher at 2, 4, and 8 weeks; Tb.Sp decreased over time. Immunofluorescence showed significantly higher ALP and Runx2 expression, fewer iNOS⁺/CD68⁺ cells, more CD206⁺/CD68⁺ cells, and more CD31⁺ cells in PLAM-10 vs. other groups (p<0.05–0.001).
**Clinical Implications:** This Janus PLAM-MPN membrane offers a simple, low-cost, scalable approach combining barrier function with bioactive bone regeneration. The MPN coating provides immunomodulatory, pro-angiogenic, and osteoinductive effects without exogenous growth factors. The use of FDA-approved PLA and naturally-derived polyphenols/metal ions supports translational potential. However, PEG used in fabrication may cause immunogenicity, requiring alternative pore-forming techniques before clinical use. The MPN coating strategy is generalizable to other barrier membranes and tissue engineering scaffolds.