RESUMEN
Introduction: Hydroxylapatite (HAp) is a biodegradable bone graft material with high biocompatibility. However, the clinical application of HAp has been limited due to the poor absorption rate in vivo. Methods: In this study, carbonated hydroxylapatite (CHAp) with a chemical composition similar to natural bone was synthesized. HAp and CHAp scaffolds were fabricated by 3D printing. Each material was designed by two types of scaffold model with a maximum width of 8 mm and a thickness of 2 mm, ie, structure I (round shape) and structure II (grid shape). Then, the HAp scaffolds were loaded with lutein. These scaffolds were implanted into the 8 mm bone defect on the top of the rabbit skull within 3 hours in the morning. The curative effects of the scaffolds were assessed two months after implantation. Results: The 3D printed scaffolds did not cause severe inflammation or rejection after implantation. It showed that the porous structures allow bone cells to enter into the scaffolds. Furthermore, CHAp scaffolds were more biocompatible than HAp scaffolds, and showed a higher level of degradation and new bone formation after implantation. Structure II scaffolds with a smaller mineral content degraded faster than structure I, while structure I had better osteoconductive properties than structure II. Besides, the addition of lutein significantly enhanced the rate of new bone formation. Discussion: The uniqueness of this study lies in the synthesis of 3D printed CHAp scaffolds and the implantation of CHAp in rabbit bone defects. The incorporation of suitable carbonate and lutein into HAp can enhance the osteoinductivity of the graft, and CHAp has a faster degradation rate in vivo, all of which provide a new reference for the research and application of apatite-based composites.
Asunto(s)
Materiales Biocompatibles , Durapatita , Animales , Conejos , Durapatita/química , Materiales Biocompatibles/química , Andamios del Tejido/química , Luteína , Regeneración Ósea , Cráneo/cirugía , Impresión Tridimensional , Osteogénesis , Ingeniería de Tejidos/métodos , PorosidadRESUMEN
Cadmium (Cd) is an important environmental toxicant that could cause serious damage to various organs including severe hepatotoxicity in intoxicated animals. Selenium has been reported to possess the protective effects against Cd toxicity, but the specific mechanism is still unclear. The purpose of this study was to explore the effects and mechanism of chitosan coated selenium nanoparticles (CS-SeNPs) against Cd-induced hepatotoxicity in animal and cellular models. ICR mice and rat hepatocyte BRL-3A cells were exposed to cadmium chloride (CdCl2) to evaluate the therapeutic efficiency of CS-SeNPs. Analysis of histopathological images, mitochondrial membrane potential (MMP) and ultramicrostructure, serum liver enzyme activities, ferroptosis-related indicators contents, and further molecular biology experiments were performed to investigate the underlying mechanisms. In vivo experiment results showed that CdCl2 caused significant pathological damage involving significant increase of liver index, contents of tissue MDA and serum ALT and AST, and significant decrease of serum GSH-Px activity. Moreover, CdCl2 exposure upregulated ACSL4 and HO-1 protein levels, downregulated GPX4, TfR1, ferritin protein levels in the liver. Notably, CS-SeNPs increased the expression level of GPX4 and ameliorated CdCl2-induced changes in above-mentioned indicators. In vitro experimental results showed that treatment with CS-SeNPs significantly elevated GSH-Px activity and GPX4 protein level, reversed CdCl2-induced expression of several ferroptosis-related proteins TfR1, FTH1 and HO-1, and repressed ROS production and increased MMP of the cells exposed to CdCl2. Our research indicated that CdCl2 induced hepatocyte injury by inducing ferroptosis, while CS-SeNPs can inhibit ferroptosis and reduce the degree of hepatocyte injury. This study is of great significance for further revealing the mechanism of Cd hepatotoxicity and expanding the clinical application of SeNPs.