Anti‐Inflammatory Yerba Mate‐Loaded Electrospun Polycaprolactone/Gelatin Membranes for the Management of Endodontic‐Periodontal Lesions

Combined endodontic‐periodontal diseases require integrated endodontic and periodontal treatment. However, extensive bone loss can limit the use of conventional approaches, necessitating regenerative methods such as guided tissue regeneration to manage intrabony defects. Yerba mate (YM, Ilex paraguariensis ) exhibits antioxidant and anti‐inflammatory properties and has been shown to reduce osteoclastogenesis and inflammation‐associated bone loss, supporting its potential as a bioactive compound for incorporation into guided tissue regeneration biomaterials. This study aimed to develop and characterize polycaprolactone (PCL)/gelatin (Gel) scaffolds containing YM via electrospinning to support mineralized tissue formation and control inflammation. Electrospun PCL/Gel scaffolds, with and without YM, were obtained using optimized parameters and then chemically crosslinked. Fiber morphology and composition were assessed by scanning electron microscopy (SEM) and Fourier‐transform infrared spectroscopy (FTIR), and swelling, degradation, and mechanical properties were evaluated. Biological characterization used periodontal ligament stem cells (PDLSCs) cultured on the scaffolds to assess metabolic activity, adhesion/spreading, and mineralized matrix deposition. The immunomodulatory effect of scaffold extracts was evaluated in Escherichia coli LPS‐challenged macrophages (RAW 264.7) by measuring TNF‐α, IL‐6, and IL‐1α. Biocompatibility and collagen deposition were further assessed in vivo in the subcutaneous tissue of rats at 7 and 28 days. Data were analyzed using appropriate tests ( α = 5%). Bead‐free fibers formed regardless of YM incorporation, and YM increased fiber diameter after crosslinking ( p < 0.0001). Young's modulus and elongation at break were unchanged, although YM reduced tensile strength ( p = 0.0107). YM incorporation was non‐cytotoxic and did not impair mineralization, while reducing IL‐6 and TNF‐α without affecting IL‐1α. In vivo, YM‐loaded scaffolds significantly reduced the inflammatory infiltrate at both time points without altering collagen deposition. These findings demonstrate that YM can be electrospun with PCL/Gel to produce cytocompatible, anti‐inflammatory membranes with potential for endo‐perio lesion management.