Autocrine TGF‐β1 in Periodontal Ligament‐Derived Stem Cell Pellets Enhances Periodontal Regeneration in Class II Furcation Defects of Canine Models

The Class II furcation defects present a significant challenge in periodontal treatment and pose a considerable risk to tooth survival. While scaffold-free Periodontal ligament stem cells (PDLSCs)-derived cell pellets (CP) and sheets (CS) aid regeneration, the molecular mechanisms and efficacy of PDLSC-CP remain unclear, especially in large animals. This study investigates PDLSC-CP's regenerative potential for Class II defects through in vitro and in vivo analyses. PDLSC-CP demonstrated superior cell viability, improved the extracellular matrix (ECM) quality, enhanced biomechanical properties, and a greater potential for periodontal tissue regeneration compared to PDLSC-CS in both in vitro and in vivo scenarios. Importantly, autocrine transforming growth factor-β1 (TGF-β1) in PDLSC-CP upregulated odonto/osteogenesis-related factors by activating the TGF-β1/Smad pathway. However, LY2109761, an inhibitor of TGF-β receptor I and II, suppressed periodontal tissue regeneration in immunodeficient mice. In the beagle dog with Class II furcation defects, PDLSC-CP regenerated and repaired periodontal bone defects, which is more effective than the control group, the bone substitutes group, and the mixed group (PDLSC-CP and bone substitutes). These findings highlight PDLSC-CP as a promising strategy for periodontal bone defect treatment, where autocrine TGF-β1 stimulates the TGF-β1/Smad pathway to drive periodontal tissue regeneration.