Zinc finger-inspired peptide-metal-phenolic nanointerface enhances bone-implant integration under bacterial infection microenvironment through immune modulation and osteogenesis promotion  

作　　者：Lin Xu Jie Fang Jiezhou Pan Hexu Qi Yun Yin Yunxiang He Xueqi Gan Yifei Li Yu Li Junling Guo 

机构地区：[1]State Key Laboratory of Oral Diseases,National Center for Stomatology,National Clinical Research Center for Oral Diseases,Department of Orthodontics,West China Hospital of Stomatology,Sichuan University,Chengdu,610041,China [2]Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE,Department of Pediatric Dentistry,West China Second University Hospital,Sichuan University,Chengdu,610041,China [3]BMI Center for Biomass Materials and Nanointerfaces,College of Biomass Science and Engineering,Sichuan University,Chengdu,610065,China [4]State Key Laboratory of Oral Diseases,National Center for Stomatology,National Clinical Research Center for Oral Diseases,Department of Prosthodontics,West China Hospital of Stomatology,Sichuan University,Chengdu,610041,China [5]Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE,Department of Pediatrics,West China Second University Hospital,Sichuan University,Chengdu,610041,China [6]National Engineering Laboratory for Clean Technology of Leather Manufacture,Sichuan University,Chengdu,610065,China [7]State Key Laboratory of Polymer Materials Engineering,Sichuan University,Chengdu,610065,China [8]Bioproducts Institute,Department of Chemical and Biological Engineering,The University of British Columbia,Vancouver,BC,V6T 1Z4,Canada

出　　处：《Bioactive Materials》2024年第11期564-576,共13页生物活性材料（英文）

基　　金：National Natural Science Foundation of China(J.F.,Grant no.32000928);Sichuan Science and Technology Program(J.F.,Grant no.2023YFS0150);National Natural Science Foundation of China(Y.L.,Grant no.82270249);National Key R&D Program of China(J.G.,Grant No.2022YFA0912800);National Natural Science Foundation of China(J.G.,Grant No.22178233);National Excellent Young Scientist Fund(J.G.,Grant No.00308054A1045);Sichuan Tianfu Emei Project(J.G.,Grant No.2022-EC02-00073-CG);Talents Program of Sichuan Province(J.G.);Double First Class University Plan of Sichuan University(J.G.);State Key Laboratory of Polymer Materials Engineering(J.G.,Grant No.sklpme 2020-03-01);National Natural Science Foundation of China(Y.L.,Grant no.31971247,82371003).

摘　　要：Orthopedic and dental implantations under bacterial infection microenvironment face significant challenges in achieving high-quality bone-implant integration. Designing implant coatings that incorporate both immune defense and anti-inflammation is difficult in conventional single-functional coatings. We introduce a multifunctional nanointerface using a zinc finger-inspired peptide-metal-phenolic nanocoating, designed to enhance implant osseointegration under such conditions. Abaloparatide (ABL), a second-generation anabolic drug for treating osteoporosis, can be integrated into the design of a zinc-phenolic network constructed on the implant surface (ABL@ZnTA). Importantly, the phenolic-coordinated Zn2+ ions in ABL@ZnTA can act as zinc finger motif to co-stabilize the configuration of ABL through multiple molecular interactions, enabling high bioactivity, high loading capacity (1.36 times), and long-term release (>7 days) of ABL. Our results showed that ABL@ZnTA can modulate macrophage polarization from the pro-inflammatory M1 towards the anti-inflammatory M2 phenotype, promoting immune osteogenesis with increased OCN, ALP, and SOD 1 expression. Furthermore, the ABL@ZnTA significantly reduces inflammatory fibrous tissue encapsulation and enhances the long-term stability of the implants, indicated by enhanced binding strength (6 times) and functional connectivity (1.5−3 times) in the rat bone defect model infected by S. aureus. Overall, our research offers a nano-enabled synergistic strategy that balances infection defense and osteogenesis promotion in orthopedic and dental implantations.

关 键 词：Metal-phenolic network IMPLANT OSSEOINTEGRATION Inflammation Abaloparatide 

分 类 号：R318[医药卫生—生物医学工程]