IADR Abstract Archives
Delayed Post-Extraction Healing in Mice Lacking Initial Oral Mucosal Lymphatics
Objectives: Lymphatics are important for resolution of inflammation, but their role in the oral wound healing process is insufficiently studied. The aim of this study was to investigate mucosal and bone healing responses following extraction of maxillary second molars in a transgenic mouse model lacking initial lymphatics in oral mucosa.
Methods: Second bilateral maxillary molars were extracted in wild type (WT, C57/Bl6) and transgenic K14-VEGFR3-IgG mice. The animals were sacrificed on day 7, 14 or 21 post-extraction and jaws were removed. Mucosal wound closure was clinically assessed and measured under a photomicroscope. Bone healing was evaluated by micro-CT analysis following PFA fixation. Inflammatory infiltrates were immunohistochemically evaluated in the same jaws. Proteins were extracted from contralateral jaws and subjected to proteomic profiling and multiplex analyses for different cytokines.
Results: Wound closures occurred faster in WT than transgenic mice, with a clear difference on day 14. Trabecular bone developed in both mice strains over 21 days, it was however significantly decreased after 14 days in K14-VEGFR3 mice compared with WT controls. Bone mineral density was also significantly lower at day 14 in the transgenic group. Rich infiltrates of neutrophils were seen at day 7 in both groups, with increased infiltrates in transgenic mice up to 14 days in wounds with incomplete healing. Blood vessels were abundant at all observation times in both mice strains, while lymphatics were identified within the wounds of WT mice alone. Epithelial growth factor (EGF) expression was significantly higher in WT compared with transgenic mice at all observation times, while C-reactive protein (CRP) showed elevated values in K14-VEGFR3 compared with WT mice. Chemokine-ligand 21 (CCL21) was only expressed in WT gingiva, and significantly higher in WT bone samples compared with transgenic samples.
Conclusions: Lack of initial lymphatic vessels delayed wound healing responses in mucosa and bone after tooth extractions in mice.
Methods: Second bilateral maxillary molars were extracted in wild type (WT, C57/Bl6) and transgenic K14-VEGFR3-IgG mice. The animals were sacrificed on day 7, 14 or 21 post-extraction and jaws were removed. Mucosal wound closure was clinically assessed and measured under a photomicroscope. Bone healing was evaluated by micro-CT analysis following PFA fixation. Inflammatory infiltrates were immunohistochemically evaluated in the same jaws. Proteins were extracted from contralateral jaws and subjected to proteomic profiling and multiplex analyses for different cytokines.
Results: Wound closures occurred faster in WT than transgenic mice, with a clear difference on day 14. Trabecular bone developed in both mice strains over 21 days, it was however significantly decreased after 14 days in K14-VEGFR3 mice compared with WT controls. Bone mineral density was also significantly lower at day 14 in the transgenic group. Rich infiltrates of neutrophils were seen at day 7 in both groups, with increased infiltrates in transgenic mice up to 14 days in wounds with incomplete healing. Blood vessels were abundant at all observation times in both mice strains, while lymphatics were identified within the wounds of WT mice alone. Epithelial growth factor (EGF) expression was significantly higher in WT compared with transgenic mice at all observation times, while C-reactive protein (CRP) showed elevated values in K14-VEGFR3 compared with WT mice. Chemokine-ligand 21 (CCL21) was only expressed in WT gingiva, and significantly higher in WT bone samples compared with transgenic samples.
Conclusions: Lack of initial lymphatic vessels delayed wound healing responses in mucosa and bone after tooth extractions in mice.