Detection of senescent cells in the mucosal healing process on type 2 diabetic rats after tooth extraction for biomaterial development.

The delayed mucosal healing of tooth extraction sockets in diabetes has few known effective treatment strategies, and its underlying mechanism remains unknown. Senescent cells may play a pivotal role in this delay, given the well-established association between diabetes, senescent cells, and wound healing. Here, we demonstrated an increase in p21- or p16-positive senescent cells in the epithelial and connective tissues of extraction sockets in type 2 diabetic rats compared to those in control rats. Between 7 and 14 days after tooth extraction, a decrease in senescent cells and improvement in re-epithelialization failure were observed in the epithelium, while an increase in senescent cells and persistence of inflammation were observed in the connective tissue. These results suggest that cellular senescence may have been induced by diabetes and contributed to delayed mucosal healing by suppressing re-epithelization and persistent inflammation. These findings provide new targets for treatment using biomaterials, cells, and drugs.

Senolytics ameliorate the failure of bone regeneration through the cell senescence-related inflammatory signalling pathway.

Stress-induced premature senescent (SIPS) cells induced by various stresses deteriorate cell functions. Dasatinib and quercetin senolytics (DQ) can alleviate several diseases by eliminating senescent cells. α-tricalcium phosphate (α-TCP) is a widely used therapeutic approach for bone restoration but induces bone formation for a comparatively long time. Furthermore, bone infection exacerbates the detrimental prognosis of bone formation during material implant surgery due to oral cavity bacteria and unintentional contamination. It is essential to mitigate the inhibitory effects on bone formation during surgical procedures. Little is known that DQ improves bone formation in Lipopolysaccharide (LPS)-contaminated implants and its intrinsic mechanisms in the study of maxillofacial bone defects. This study aims to investigate whether the administration of DQ ameliorates the impairments on bone repair inflammation and contamination by eliminating SIPS cells. α-TCP and LPS-contaminated α-TCP were implanted into Sprague-Dawley rat calvaria bone defects. Simultaneously, bone formation in the bone defects was investigated with or without the oral administration of DQ. Micro-computed tomography and hematoxylin-eosin staining showed that senolytics significantly enhanced bone formation at the defect site. Histology and immunofluorescence staining revealed that the levels of p21- and p16-positive senescent cells, inflammation, macrophages, reactive oxygen species, and tartrate-resistant acid phosphatase-positive cells declined after administering DQ. DQ could partially alleviate the production of senescent markers and senescence-associated secretory phenotypes in vitro. This study indicates that LPS-contaminated α-TCP-based biomaterials can induce cellular senescence and hamper bone regeneration. Senolytics have significant therapeutic potential in reducing the adverse osteogenic effects of biomaterial-related infections and improving bone formation capacity.