Bone infection is a catastrophe in clinical orthopedics.Despite being the standard therapy for osteomyelitis,antibiotic-loaded polymethyl methacrylate(PMMA)cement has low efficiency against bacteria in biofilms.Furthe...Bone infection is a catastrophe in clinical orthopedics.Despite being the standard therapy for osteomyelitis,antibiotic-loaded polymethyl methacrylate(PMMA)cement has low efficiency against bacteria in biofilms.Furthermore,high-dose antibiotic-loaded implants carry risks of bacterial resistance,tissue toxicity,and impairment of local tissue healing.By incorporating borosilicate bioactive glass(BSG)into low-dose gentamicin sulfate(GS)-loaded PMMA cement,an intelligent strategy that synergistically eradicates bacteria and sequen-tially promotes osseointegration,was devised.Results showed that BSG did not compromises the handling properties of the cement,but actually endowed it with an ionic and alkaline microenvironment,thereby damaging the integrity of bacterial cell walls and membranes,inhibiting ATP synthesis by disrupting the res-piratory chain in cell membranes and glycogen metabolism,and elevating reactive oxygen species(ROS)levels by weakening antioxidant components(peroxisomes and carotenoids).These antibacterial characteristics of BSG synergistically reinforced the effectiveness of GS,which was far below the actual clinical dosage,achieving efficient bacterial killing and biofilm clearance by binding to the 30S subunit of ribosomes.Furthermore,the released GS and the ionic and alkaline microenvironment from the implants fostered the osteogenic activity of hBMSCs in vitro and coordinately enhanced osseointegration in vivo.Collectively,this study underscores that BSG incorporation offers a promising strategy for reducing antibiotic dosage while simultaneously enhancing the antibacterial activity and osteogenesis of implants.This approach holds potential for resolving the conflict be-tween bacterial resistance and bone infection.展开更多
基金supported by the National Key R&D Program of China(Grant No.2023YFC2416900)the National Natural Science Foundation of China(Grant No.U22A20357,52072398,82102584 and 32161160327)+1 种基金Shenzhen Science and Technology Program(Grant No.JCYJ20230807140714030,JCYJ20220818101613028,and JSGGKQTD20210831174330015)Shenzhen Medical Research Found(B2302031).
文摘Bone infection is a catastrophe in clinical orthopedics.Despite being the standard therapy for osteomyelitis,antibiotic-loaded polymethyl methacrylate(PMMA)cement has low efficiency against bacteria in biofilms.Furthermore,high-dose antibiotic-loaded implants carry risks of bacterial resistance,tissue toxicity,and impairment of local tissue healing.By incorporating borosilicate bioactive glass(BSG)into low-dose gentamicin sulfate(GS)-loaded PMMA cement,an intelligent strategy that synergistically eradicates bacteria and sequen-tially promotes osseointegration,was devised.Results showed that BSG did not compromises the handling properties of the cement,but actually endowed it with an ionic and alkaline microenvironment,thereby damaging the integrity of bacterial cell walls and membranes,inhibiting ATP synthesis by disrupting the res-piratory chain in cell membranes and glycogen metabolism,and elevating reactive oxygen species(ROS)levels by weakening antioxidant components(peroxisomes and carotenoids).These antibacterial characteristics of BSG synergistically reinforced the effectiveness of GS,which was far below the actual clinical dosage,achieving efficient bacterial killing and biofilm clearance by binding to the 30S subunit of ribosomes.Furthermore,the released GS and the ionic and alkaline microenvironment from the implants fostered the osteogenic activity of hBMSCs in vitro and coordinately enhanced osseointegration in vivo.Collectively,this study underscores that BSG incorporation offers a promising strategy for reducing antibiotic dosage while simultaneously enhancing the antibacterial activity and osteogenesis of implants.This approach holds potential for resolving the conflict be-tween bacterial resistance and bone infection.
