Human Periodontal Ligament Cells Exosome-Loaded Biodegradable Piezoelectric Fibrous Membrane for Vascularized Periodontal Bone Regeneration

Periodontal bone destruction caused by periodontitis, surgery, or trauma results in loss of periodontal ligament attachment, which in turn leads to tooth mobility and tooth loss. Complete periodontal bone reconstruction remains challenging. Periodontal ligament mesenchymal stem cells (PDLSCs) are a crucial cellular resource for regenerating and repairing periodontal bone defects. As a cell-free therapeutic approach, exosomes (Exos) derived from PDLSCs represent a promising and effective cell-free therapeutic strategy for inducing neo-bone growth. Due to the electrophysiological features of native bone, this study proposed the use of a piezoelectric fibrous membrane as the delivery carrier for Exos in guided tissue/bone regeneration therapy, synergistically promoting periodontal bone regeneration. The membrane was composed of poly(l-lactide)/gelatin, fabricated via electrospinning, and coated with polydopamine for Exos loading and sustained release. The piezoelectricity of the membrane came from the poly(l-lactide) after polarization. The material electroactivity and the bioactive Exos combinedly created a microenvironment conducive to cell recruitment, proliferation, angiogenic and osteogenic differentiation. In rat periodontal bone defect models, piezoelectric membranes functionalized with PDLSC-Exos significantly enhanced bone regeneration compared to membranes lacking Exos or piezoelectric properties. Collectively, this study provided valuable new insights to design biomimetic membranes with enhanced angiogenesis and osteogenesis properties for vascularized periodontal bone regeneration and other applications.