Hydrogels have been widely applied to the fabrication of tissue engineering scaffolds via three-dimensional (3D) bioprinting because of their extracellular matrix-like properties, capacity for living cell encapsulation, and shapeable customization depending on the defect shape. However, the current hydrogel scaffolds show limited regeneration activity, especially in the application of periodontal tissue regeneration. In this study, we attempted to develop a novel multi-component hydrogel that possesses good biological activity, can wrap living cells for 3D bioprinting and can regenerate periodontal soft and hard tissue. The multi-component hydrogel consisted of gelatin methacryloyl (GelMA), sodium alginate (SA) and bioactive glass microsphere (BGM), which was first processed into hydrogel scaffolds by cell-free 3D printing to evaluate its printability and in vitro biological performances. The cell-free 3D-printed scaffolds showed uniform porous structures and good swelling capability. The BGM-loaded scaffold exhibited good biocompatibility, enhanced osteogenic differentiation, apatite formation abilities and desired mechanical strength. The composite hydrogel was further applied as a bio-ink to load with mouse bone marrow mesenchymal stem cells (mBMSCs) and growth factors (BMP2 and PDGF) for the fabrication of a scaffold for periodontal tissue regeneration. The cell wrapped in the hydrogel still maintained good cellular vitality after 3D bioprinting and showed enhanced osteogenic differentiation and soft tissue repair capabilities in BMP2- and PDGF-loaded scaffolds. It was noted that after transplantation of the cell- and growth factor-laden scaffolds in Beagle dog periodontal defects, significant regeneration of gingival tissue, periodontal ligament, and alveolar bone was detected. Importantly, a reconstructed periodontal structure was established in the treatment group eight weeks post-transplantation of the scaffolds containing the cell and growth factors. In conclusion, we developed a bioactive composite bio-ink for the fabrication of scaffolds applicable for the reconstruction and regeneration of periodontal tissue defects.

This study investigates the causal relationship between rheumatoid arthritis (RA) and periodontitis (PD) using Mendelian randomization (MR) analysis in an East Asian population. This study employed a 2-sample MR analysis using genome-wide association study (GWAS) data. Single nucleotide polymorphisms (SNPs) associated with RA were selected from a GWAS dataset of 22,515 East Asian individuals (4873 RA cases and 17,642 controls). The association of these SNPs with PD was examined in a separate GWAS dataset of 212,453 East Asian individuals (3219 PD cases and 209,234 controls). The study utilized inverse variance weighted (IVW) analysis, MR-Egger regression, and the weighted median method to assess the causal effect of RA on PD. The IVW analysis demonstrated a statistically significant but modest inverse association between genetically predicted RA and PD risk (odds ratio = 0.931, 95% confidence interval 0.886–0.978, P = .005). No statistical evidence of directional horizontal pleiotropy was detected in the MR-Egger regression (Egger intercept = −0.005, P = .821), and Cochran Q test did not indicate substantial heterogeneity across instruments ( P = .168). The direction and magnitude of the association were broadly consistent across the different MR methods applied. Leave-one-out sensitivity analyses did not identify any single SNP that disproportionately influenced the overall estimates. In this 2-sample Mendelian randomization study of East Asian populations, genetically predicted RA liability showed a statistically significant but modest inverse association with PD risk. The observed inverse association should be considered hypothesis-generating and does not provide definitive evidence that RA is protective against PD; further studies in other populations are needed to validate these findings and clarify the underlying mechanisms.