Zn/Cu-loaded functional bacterial cellulose modulates macrophage reprogramming to improve osteointegration and infection treatment

Abstract

Currently, large segmental bone defects due to accidents, osteomyelitis debridement surgery, and other conditions, the treatments remain difficult. Large segmental bone defects are characterized by long treatment times, poor prognoses, and infectious complications. Although metal ions play crucial roles in directing bone tissue engineering, limited research has concentrated on ion-doped bacterial cellulose’s immunomodulatory properties. Therefore, we developed a mineralized bacterial cellulose (ZnCu-CaP-BC) biomaterial loaded with zinc and copper ions to enhance the bone immune environment and improve bone regeneration, as well as achieve anti-infection effects. The successful preparation of a mineralized bacterial cellulose biomaterial doped with Zn/Cu ions was confirmed by material characterization and biocompatibility experiments. Moreover, in vitro experiments demonstrated that the developed biomaterial has strong antimicrobial properties and can stimulate macrophages to improve the bone immune microenvironment by both reprogramming macrophages from the M1 to M2 phenotype and increasing the expression of alkaline phosphatase (ALP) and osteoclastogenic protein (OCN). The study performed in vivo experiments to further validate the bone-enhancing and antimicrobial properties of this biomaterial by using a rat femoral condylar defect and subcutaneous infection model. Overall, owing to the excellent antimicrobial, immunomodulatory, and bone-enhancing effects of ZnCu-CaP-BC, this material has great potential in the future.