DLP 3D-printed biomimetic periodontium composite with xenogenic treated dentin matrix modulates periodontal regeneration and inflammatory response.

Xenogeneic treated dentin matrix (xTDM) roots serve as a promising donor source for tooth replantation. Nevertheless, the regeneration of the alveolar bone-periodontal ligament (PDL)-cementum complex persists as a challenging task owing to tissue heterogeneity, limited vascularization, and immune-associated complications. In this study, a biomimetic tubular periodontium was fabricated through digital light processing (DLP)-based 3D bioprinting around columnar xTDM roots. The bio-ink was composed of silk fibroin methacrylate (SilMA), dental follicle stem cells (DFCs), and transforming growth factor-β1 (TGF-β1). In a rat subcutaneous model, the DLP Bioprinting Periodontium (DLBPB) enhanced the formation of Sharpey's fiber-like bundles with aligned orientation surrounding the xTDM. To address immune rejection, local FTY720 administration down-regulated TNF-α and IL-1β expression and induced macrophage polarization from the M1 toward the M2 phenotype. Co-delivery of TGF-β1 and FTY720 exerted synergistic immunomodulatory effects. RNA sequencing revealed downregulation of Card9 and inhibition of NF-κB signaling, thereby reducing inflammatory mediator expression. This study proposes a modular strategy that integrates biomimetic scaffold design, stem-cell-based biofabrication, and localized immunomodulation to promote functional periodontal regeneration around xTDM. Therapeutic efficacy was verified in a Beagle dog orthotopic tooth replantation model, suggesting the translational potential of DLPBP for clinical functional tooth restoration.