Fabrication And Biological Effect Investigation Of The Antibacterial Drug Delivery System With PEG-hydrogel And Cross-linked Starch On Titanium Surface

Objective To fabricate an antibacterial controlled drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface,and to investigate the surface characteristics,swelling behavior,drug release behavior in vitro,anti-infection performance in vivo,and tissue biocompatibility of the system.Methods Cross-linked starch(CSt)was synthesized first.Make CSt loaded with Gentamicin(GEN)as a carrier,preparating drug-loaded hydrogel by ultrasonic mixing with 4-arm-polyethylene glycol(PEG).Cover the surface of titanium(Ti)with a layer of poly dopamine(PDA)by Michael addition reaction.Fix the duag-loaded hydrogel to the titanium surface by casting or sol-gel dip coating methods,subsequently capped by poly lactic-co-glycolic acid(PLGA)membranes,to fabricate the Ti-PDA-PEG(GEN@CSt)-PLGA composite coating finally.Surface morphology of the system was observed by scanning electron microscope(SEM),while the swelling behavior was characterized by weighing method;release behavior of the composite coating was detected by high performance liquid chromatography(HPLC);the bacteriostatic experiments were carried out with Staphylococcus aureus(SAU),Staphylococcus epidermidis(SEP)and Escherichia coli(ECO)in vitro.The animal models of infected bone defect was established in 36 New Zealand white rabbits.After randomization,different materials were implanted into the animals,the infection data were collected periodically to carry out anti-infection experiments in vivo.Another 12 rabbits were divided into the experimental group and the control group randomly.Biocompatibility of the materials was observed by histopathology after implantation of the corresponding materials into the femoral condyle.Results The composite coating adhered to the titanium surface firmly,presenting a smooth and translucent shape.The ratio of CSt/PEG affects swelling behavior,the swelling decreases with the increase of CSt Ratio.In-vitro release showed that the release rate of the first 8 H was fast,and the cumulative release amount accounted for 83%of the total in the first 7 days,lasting more than 13 D.In vitro antibacterial test,the composite coating formed obvious bacteriostatic rings in three kinds of bacteria.In-vivo anti-infection experiment showed that the infection situation of the experimental group was better than the control group.The pathological results indicated that inflammatory reaction in the experimental group was basically the same as the control group.Conclusion The study successfully fabricated the antibacterial controlled drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface.The system has a reasonable drug release behavior,and effectively inhibited the growth of bacteria in vivo and in vitro.It also has good biocompatibility to stand a promising strategy to improve the orthopedics anti-infection.