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.

The reconstruction of craniomaxillofacial bone defects remains clinically challenging.To date,autogenous grafts are considered the gold standard but present critical drawbacks.These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques.Among the various fabrication methods,additive manufacturing(AM)has shown significant clinical potential.AM technologies build three-dimensional(3D)objects with personalized geometry customizable from a computer-aided design.These layer-by-layer 3D biomaterial structures can support bone formation by guiding cell migration/proliferation,osteogenesis,and angiogenesis.Additionally,these structures can be engineered to degrade concomitantly with the new bone tissue formation,making them ideal as synthetic grafts.This review delves into the key advances of bioceramic grafts/scaffolds obtained by 3D printing for personalized craniomaxillofacial bone reconstruction.In this regard,clinically relevant topics such as ceramic-based biomaterials,graft/scaffold characteristics(macro/micro-features),material extrusion-based 3D printing,and the step-by-step workflow to engineer personalized bioceramic grafts are discussed.Importantly,in vitro models are highlighted in conjunction with a thorough examination of the signaling pathways reported when investigating these bioceramics and their effect on cellular response/behavior.Lastly,we summarize the clinical potential and translation opportunities of personalized bioceramics for craniomaxillofacial bone regeneration.

The reconstruction of craniomaxillofacial bone defects remains clinically challenging.To date,autogenous grafts are considered the gold standard but present critical drawbacks.These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques.Among the various fabrication methods,additive manufacturing(AM)has shown significant clinical potential.AM technologies build three-dimensional(3D)objects with personalized geometry customizable from a computer-aided design.These layer-by-layer 3D biomaterial structures can support bone formation by guiding cell migration/proliferation,osteogenesis,and angiogenesis.Additionally,these structures can be engineered to degrade concomitantly with the new bone tissue formation,making them ideal as synthetic grafts.This review delves into the key advances of bioceramic grafts/scaffolds obtained by 3D printing for personalized craniomaxillofacial bone reconstruction.In this regard,clinically relevant topics such as ceramic-based biomaterials,graft/scaffold characteristics(macro/micro-features),material extrusion-based 3D printing,and the step-by-step workflow to engineer personalized bioceramic grafts are discussed.Importantly,in vitro models are highlighted in conjunction with a thorough examination of the signaling pathways reported when investigating these bioceramics and their effect on cellular response/behavior.Lastly,we summarize the clinical potential and translation opportunities of personalized bioceramics for craniomaxillofacial bone regeneration.