HUANG Yixing,ZHENG Zhenyu,XU Guochao, et al. Preparation of intelligent responsive anti-infection coating based on hyaluronidase activity[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(9): 706-713.
Abstract:Objective: To prepare an anti-infection coating on the surface of bone implants that can achieve enzyme and bacterial responsive release of antibiotics. Methods: After the (MMT/HA-VA)5 coating structure was successfully loaded on the substrate surface by layer-on-layer assembly technology, the variation in surface roughness was observed; and after contact with bacteria and enzymes, the surface morphology, the size of antibacterial ring and the thickness of coating were observed. The antibacterial effect of multilayer coatings was evaluated by detecting the bacterial contents. Its biocompatibility and antibacterial effect in vivo were tested by cell and animal experiments. Results: As the antibacterial coating was assembled, the surface roughness of (MMT/HA-VA)5 coating increased compared with that of (MMT/HA-VA)1 coating (P<0.05). The coating was disintegrated to varying degrees after contact with enzymes or bacteria, and the changes in bacteriostasis ring and coating thickness also showed a concentration dependence (P<0.05). At each time point, the content of extracellular alkaline phosphatase, potassium ion, protein and nucleic acid in (MMT/HA-VA)5 group was higher than in the blank group. Cytocompatibility test showed that the coating extract had no significant adverse effect on the actin filament and nucleus of MC3T3 cells. In the in vivo experiment, there were significant differences on TNF-α level between the infection group and (MMT/HA-VA)5 group (P<0.05). However, there was no significant difference in TNF-α level between the (MMT/HA-VA)5 group and the blank group (P>0.05). A large number of bacteria were detected on the surface of Kirschner’s needles in the infection group, but neither in the (MMT/HA-VA)5 group nor in the blank group. HE staining of bone tissue showed a large number of inflammatory cells in the infection group, while the bone structure of the (MMT/HA-VA)5 group and the blank group was normal.Conclusion: The (MMT/HA-VA)5 composite multilayer antibacterial coating can automatically adjust the dosage of antibiotic sustained release according to the severity of infection, thus achieving precise prevention and efficient sterilization of infections related to bone implants.