ABSTRACT
Background: Wound healing is a complex biological process that can be impaired in individuals with diabetes. Diabetic wounds are a serious complication of diabetes that require promoting diagnosis and effective treatment. FGF-21, a member of the endocrine FGF factors family, has caught the spotlight in the treatment of diabetes for its beneficial effects on accelerating human glucose uptake and fat catabolism. However, the therapeutic efficacy of FGF-21 in promoting diabetic wounds remains unknown. This study aims to evaluate the therapeutic potential of FGF-21 in promoting diabetic wound healing. Methods: we investigated the effects of FGF-21 on wound healing related-cells under high-glucose conditions using various assays such as CCK8, scratch assay, flow cytometry analysis, endothelial tube-formation assay, and transmission electron microscopy. Furthermore, we used db/db mice to verify the healing-promoting therapeutic effects of FGF-21 on diabetic wounds. We also conducted qRT-PCR, Western blot, and immunofluorescence staining analyses to elucidate the underlying mechanism. Result: Our results indicate that FGF-21 treatment restored hyperglycemic damage on endothelial cell proliferation, migration, and tube-forming ability. It also reduced endothelial cell death rates under high-glucose conditions. TEM analysis showed that FGF-21 treatment effectively restored mitochondrial damage and morphological changes in endothelial cells caused by glucose. Additionally, qRT-PCR and Western blot analysis indicated that FGF-21 treatment restored inflammatory responses caused by hyperglycemic damage. Animal experiments confirmed these findings, suggesting that FGF-21 may be a promising candidate for the treatment of non-healing diabetic wounds due to its effectiveness in stimulating angiogenesis and anti-inflammatory function. Conclusion: Our study provides evidence that FGF-21 is an essential regulator of wound-related cells under high-glucose conditions and has the potential to be a novel therapeutic target for accelerating diabetic wound healing.
ABSTRACT
Osseointegration between implants and bone tissue lays the foundation for the long-term stability of implants. The incorporation of a porous structure and local slow release of siRNA to silence casein kinase-2 interacting protein-1 (CKIP-1), a downregulator of bone formation, is expected to promote osseointegration. Here, porous implants with a porous outer layer and dense inner core were prepared by metal coinjection molding (MIM). Mg-doped calcium phosphate nanoparticles (CaPNPs)-grafted arginine-glycine-aspartate cell adhesion sequence (RGD) and transcribed activator (TAT) (MCPRT)/CKIP-1 siRNA complex and polylysine (PLL) were coated onto the surface of the porous implants by layer-by-layer (LBL) self-deposition. The in vitro results showed that the MCPRT-siRNA coating promoted MG63 cell adhesion and proliferation, enhanced the protein expressions (ALP and OC) and bone formation-related gene expression (OPN, OC and COL-1α) in vitro. The in vivo results demonstrated that the porous structure enhanced bone ingrowth and that the local slow release of MCPRT-siRNA accelerated new bone formation at the early stage. The porous structure coupled with local CKIP-1 siRNA delivery constitutes a promising approach to achieve faster and stronger osseointegration for dental implants.
