Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi.

Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.

Advances in materials-based therapeutic strategies against osteoporosis.

Osteoporosis is caused by the disruption in homeostasis between bone formation and bone resorption. Conventional management of osteoporosis involves systematic drug administration and hormonal therapy. These treatment strategies have limited curative efficacy and multiple adverse effects. Biomaterials-based therapeutic strategies have recently emerged as promising alternatives for the treatment of osteoporosis. The present review summarizes the current status of biomaterials designed for managing osteoporosis. The advantages of biomaterials-based strategies over conventional systematic drug treatment are presented. Different anti-osteoporotic delivery systems are concisely addressed. These materials include injectable hydrogels and nanoparticles, as well as anti-osteoporotic bone tissue engineering materials. Fabrication techniques such as 3D printing, electrostatic spinning and artificial intelligence are appraised in the context of how the use of these adjunctive techniques may improve treatment efficacy. The limitations of existing biomaterials are critically analyzed, together with deliberation of the future directions in biomaterials-based therapies. The latter include discussion on the use of combination strategies to enhance therapeutic efficacy in the osteoporosis niche.

Inflammation-associated ectopic mineralization.

Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues. Calcific aortic valve disease, vascular calcification, gallstones, kidney stones, and abnormal mineralization in arthritis are common examples of ectopic mineralization. They are debilitating diseases and exhibit excess mortality, disability, and morbidity, which impose on patients with limited social or financial resources. Recent recognition that inflammation plays an important role in ectopic mineralization has attracted the attention of scientists from different research fields. In the present review, we summarize the origin of inflammation in ectopic mineralization and different channels whereby inflammation drives the initiation and progression of ectopic mineralization. The current knowledge of inflammatory milieu in pathological mineralization is reviewed, including how immune cells, pro-inflammatory mediators, and osteogenic signaling pathways induce the osteogenic transition of connective tissue cells, providing nucleating sites and assembly of aberrant minerals. Advances in the understanding of the underlying mechanisms involved in inflammatory-mediated ectopic mineralization enable novel strategies to be developed that may lead to the resolution of these enervating conditions.