Abstract: BACKGROUND: Peri-implant bone defects may affect implant stability. Platelet-rich fibrin, a second-generation autologous platelet concentrate, contains abundant growth factors and fibrin scaffolds and can facilitate bone regeneration. Nevertheless, its mechanism of action in the context of peri-implant bone defects remains to be fully investigated.
OBJECTIVE: To investigate the effects of platelet-rich fibrin on osteogenic genes, bone microstructure, and IκB kinase/inhibitor of nuclear factor-κB/nuclear factor-κB signaling pathway in rats with peri-implant bone defect using a rat tibia model to simulate peri-implant bone defects, combined with ligature-induced inflammation.  
METHODS: Thirty male Sprague-Dawley rats were selected, and 20 of them were selected to establish peri-implant bone defect model. After modeling, they were randomly divided into model group and platelet-rich fibrin group, with an average of 10 rats per group, and the remaining 10 rats were assigned to the control group. The control group and the model group were not treated with any intervention, and the platelet-rich fibrin group was treated with platelet-rich fibrin implantation at the bone defect site. After 8 weeks, Image-Pro-Plus software was used to detect the bone-implant contact rate and new bone formation rate. Micro-CT was used to detect bone microstructure changes. Hematoxylin and eosin staining was used to observe histopathological changes. Nuclear transcription factor-κB, inhibitor of nuclear factor-κB, and IκB kinase were detected by western blot assay. Expression levels of osteopontin, osteocalcin, and Runt-associated transcription factor 2 were detected by RT-PCR.
RESULTS AND CONCLUSION: (1) At 4 and 8 weeks following surgery, new bone formation rate and bone-implant contact rate were increased in both model group and platelet-rich fibrin group (P < 0.05). New bone formation rate and bone-implant contact rate in platelet-rich fibrin group were significantly higher than model group (P < 0.05). (2) Compared with the control group, the model group showed decreases in trabecular number, bone volume fraction, Lane-Sandhu histological score, and mRNA expression levels of Runt-related transcription factor 2, osteocalcin, and osteopontin (P < 0.05), along with increases in trabecular separation, IκB kinase, inhibitor of nuclear factor-κB, and nuclear factor κB protein expressions (P < 0.05). Compared with the model group, the platelet-rich fibrin group showed increases in trabecular number, bone volume fraction, Lane-Sandhu histological score, and mRNA expressions of Runt-related transcription factor 2, osteocalcin, and osteopontin (P < 0.05), along with decreases in trabecular separation, IκB kinase, inhibitor of nuclear factor-κB, and nuclear factor-κB protein expressions (P < 0.05). (3) Micro-CT showed that no new bone tissue was formed in the model group, the platelet-rich fibrin group exhibited substantial new bone formation with bridging of the bone fracture ends. (4) Hematoxylin and eosin staining showed that the platelet-rich fibrin group had good bone repair status and a large number of new bone cells were generated around the defect. Results suggested that platelet-rich fibrin could accelerate the process of bone cell repair and has a significant promoting effect on bone healing in rats with peri-implant bone defects. Platelet-rich fibrin can increase the expression level of osteogenesis-related genes, improve bone microstructure, and enhance the activity of the IκB kinase/inhibitor of nuclear factor-κB/nuclear factor κB signaling pathway.

Key words: bone defect, platelet-rich fibrin, osteoblastic gene, bone microstructure,  implant, trabecular bone, bone healing, nuclear factor-κB