Synthetic high-density lipoprotein(sHDL):a bioinspired nanotherapeutics for managing periapical bone inflammation
	    		
		   		
		   			
		   		
	    	
    	 
    	10.1038/s41368-024-00316-w
   		
        
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Dal-Fabbro RENAN
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Yu MINZHI
			        		
			        		;
		        		
		        		
		        		
			        		Mei LING
			        		
			        		;
		        		
		        		
		        		
			        		Sasaki HAJIME
			        		
			        		;
		        		
		        		
		        		
			        		Schwendeman ANNA
			        		
			        		;
		        		
		        		
		        		
			        		C.Bottino MARCO
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. Department of Cariology
			        		
		        		
	        		
        		 
        	
        	
        	
        	
            
            
            	- From:
	            		
	            			International Journal of Oral Science
	            		
	            		 2024;16(3):460-470
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
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		        	Abstract:
			       	
			       		
				        
				        	Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide-eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic high-density lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm3 and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm3(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.