Intrapalatal Injection Erythromycin-Loaded Microparticles Enhance Bone Regeneration In Periodontitis

This study evaluates the potential of ERM-loaded poly(lactic acid) microparticles (PLA14200), administered via intra-palatal injection, to enhance alveolar bone regeneration and maintain periodontal health by targeting DEL-1-dependent mechanisms. Ligature-induced periodontitis (LIP) was induced on the second molar of 8-week-old male C57BL/6J mice receiving intra-palatal injections of ERM, blank particle or PLA14200. Alveolar bone was evaluated morphometrically and histologically using alkaline phosphatase (ALP) and tartrate-resistance acid phosphatase staining. DEL1 protein expression and localization were examined using immunofluorescence staining. RNAseq analysis was performed on gingival samples collected from mice with LIP treated with one of the above formulations to assess bone-related gene during bone regeneration. Additionally, MC3T3-E1, human periodontal ligament, and primary mouse bone marrow cells were used to investigate the effect of different concentrations of ERM, blank or PLA14200 on bone metabolism. Injection of PLA14200 upregulated del1 RNA expression in gingival tissue, preventing alveolar bone loss and enhancing bone growth by inducing high DEL1 protein expression in periodontal tissue. Additionally, mice treated with PLA14200 exhibited a higher osteoblasts/osteoclasts ratio, suggesting a pro-osteogenic environment and bone regeneration. At higher concentrations, cells treated with PLA14200 exhibited increased mineralization and ALP activity compared to the control ERM-treated cells. This study suggests that PLA14200 promotes bone regeneration and helps maintain periodontal health by simultaneously enhancing osteoblast activity, inhibiting osteoclast differentiation, and modulating the inflammatory environment in disease-affected bone tissue. These effects contribute to bone and periodontal tissue regeneration.