Bioengineered Bilayer Scaffold with Dual-Modal Delivery for Alveolar Bone Regeneration in Periodontitis Therapy

Periodontitis, a prevalent and progressive infectious inflammatory disease, is characterized by alveolar bone resorption and loss of periodontal attachment, presenting a formidable challenge for complete tissue regeneration. This study develops a biomimetic dual-layer scaffold (d-ACT@MIC/SIM) featuring synchronized minocycline (MIC) release and liposome-encapsulated simvastatin (SIM) delivery for optimal periodontal repair. The scaffold featured an asymmetric architecture, comprising a dense upper layer of chitosan (CS) and sodium alginate (AL) designed to prevent epithelial downgrowth, and a porous osteoconductive lower layer of CS, AL, and β-tricalcium phosphate (β-TCP) to support cell infiltration and bone ingrowth. Physicochemical characterization confirmed that d-ACT@MIC/SIM possessed favorable biocompatibility, robust antimicrobial efficacy against periodontal pathogens, and requisite mechanical integrity. In vivo studies, following the implantation of the biomimetic dual-layer drug-loading scaffold (d-ACT@MIC/SIM) into alveolar bone defects in a rat periodontitis model for 10 weeks, demonstrated significantly enhanced alveolar bone regeneration, with a bone volume/tissue volume (BV/TV) ratio of 80.6%. Furthermore, this multifunctional scaffold exhibited synergistic capabilities in promoting osteogenic differentiation, exerting sustained antibacterial activity, and mitigating local inflammatory responses. These findings highlight the substantial therapeutic potential of this asymmetrically structured, dual drug-loading biomimetic scaffold as a promising strategy for periodontal tissue engineering and the clinical management of periodontitis.