Biomimetic bilayer electrospun membrane simulating periodontal complex for orchestrated bone and fibrous tissue...

Guided tissue regeneration (GTR) is the core therapeutic strategy for repairing periodontal hard and soft tissue defects induced by periodontitis. Nevertheless, most current barrier membranes focus solely on alveolar bone reconstruction while ignoring the precise remodeling of the ordered periodontal ligament (PDL) microstructure, which impedes the integrated regeneration of functional periodontal tissues. To overcome these limitations, this study fabricated a novel bilayer composite GTR membrane with differentiated structural designs via sequential electrospinning for the synergistic and biomimetic regeneration of periodontal hard and soft tissues. The functionally graded membrane consisted of a dense, oriented poly-(lactic-co-glycolic acid) (PLGA) nanofiber outer layer and a porous collagen inner layer incorporated with hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) biphasic nanoparticles. The collagen matrix containing 60% HA and 40% β-TCP exhibited favorable mechanical properties that satisfy the mechanical requirements for periodontal repair. The dense PLGA layer effectively blocked the infiltration of human gingival fibroblasts (HGFs), and its physical barrier property could separate the external epithelial and connective tissues from the underlying bone tissue, offering a promising basis for the remodeling of periodontal hard and soft tissue. The inner Col/60% HA/40% β-TCP composite mimicked the natural organic-inorganic bone microenvironment and markedly promoted the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells. The distinctive fibrous topography of the electrospun bilayer membrane provides contact guidance at the defect margins, facilitating the ordered regeneration and rearrangement of the periodontal ligament. In vivo rat periodontal defect experiments demonstrated that the bilayer membrane, compared with single-component membranes and commercial Bio-Gide membranes, significantly enhanced new bone formation and promoted the regeneration of ordered PDL-like fibrous structures with an orientation angle approaching that of the native periodontal ligament, achieving synchronized biomimetic regeneration of periodontal hard and soft tissues. In conclusion, this bilayer GTR membrane addresses the limited PDL reconstruction achieved by conventional barrier materials and provides a promising strategy for the targeted repair of complex periodontal defects.