Unraveling an Innate Mechanism of Pathological Mineralization-Regulated Inflammation by a Nanobiomimetic System

Pathological mineralization (PTM) often occurs under inflammation and affects the prognosis of diseases, such as atherosclerosis and cancers. However, how the PTM impacts inflammation has not been well explored. Herein, poly lactic-co-glycolic acid (PLGA)/gelatin/hydroxyapatite (HA) electrospun nanofibers are rationally designed as an ideal PTM microenvironment biomimetic system for unraveling the role of PTM on inflammation. The results demonstrate that the inflammatory response decreases continuously during the process of mineralization. When mature macromineralization forms, the inflammation almost completely disappears. Mechanistically, the PTM formation is mediated by matrix proteins, local high calcium, and cell debris (nuclei), or actively regulated by the lysosomal/plasma membrane components secreted by macrophages. These inflammatory inducible factors (calcium, cell debris, etc.) can be "buried" through PTM process, resulting in reduced immune responses. Overall, the present study demonstrates that PTM is an innate mechanism of inflammation subsidence, providing valuable insight into understanding the action of mineralization on inflammation.