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Acta Biomater. 2019 Oct 18. pii: S1742-7061(19)30702-0. doi: 10.1016/j.actbio.2019.10.023. [Epub ahead of print]

Two-staged time-dependent materials for the prevention of implant-related infections.

Author information

1
State Key Laboratory of Oral Diseases, Sichuan University, 610041 Chengdu, China; Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, 610041 Chengdu, China; National Clinical Research Center for Oral Diseases, Sichuan University, 610041 Chengdu, China.
2
State Key Laboratory of Oral Diseases, Sichuan University, 610041 Chengdu, China; National Clinical Research Center for Oral Diseases, Sichuan University, 610041 Chengdu, China.
3
West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, China.
4
National Engineering Research Center for Biomaterials, Sichuan University, 610065 Chengdu, China.
5
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.
6
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: hxu@umaryland.edu.
7
State Key Laboratory of Oral Diseases, Sichuan University, 610041 Chengdu, China; Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, 610041 Chengdu, China; National Clinical Research Center for Oral Diseases, Sichuan University, 610041 Chengdu, China. Electronic address: zhouxd@scu.edu.cn.
8
State Key Laboratory of Oral Diseases, Sichuan University, 610041 Chengdu, China; Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, 610041 Chengdu, China; National Clinical Research Center for Oral Diseases, Sichuan University, 610041 Chengdu, China. Electronic address: chenglei@scu.edu.cn.

Abstract

Infection is a main cause of implant failure. Early implant-related infections often occur in the first 4 weeks post-operation. Inhibiting bacterial adhesion and biofilm formation at the early stage and promoting subsequent implant osseointegration are important for implant success. Our previous studies demonstrated that dimethylaminododecyl methacrylate (DMADDM) provided dental materials with antibacterial effects. In the present study, DMADDM and hydroxyapatite (HA) are loaded on to the titanium (Ti) surface via poly dopamine (PDA) self-polymerization. This local DMADDM-delivery Ti is referred as Ti-PHD. Here we report the two-staged capability of Ti-PHD: (1) in the first stage, releasing DMADDM during the high-infection-risk initial period post-implantation for 4 weeks; (2) then in the second stage, enhancing osteogenesis and promoting osseointegration. Ti-PHD has a porous surface with higher average roughness and greater hydrophilicity than pure Ti. Its biocompatibility is verified in vitro and in vivo. During the first 4 weeks of release, both DMADDM remaining on Ti surface and DMADDM released into the soaking medium greatly reduced the adherence and growth of pathogens. This is further confirmed by the prevention of bone destruction in a rat osteomyelitis model. After releasing DMADDM for 4 weeks, Ti-PHD promotes osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and new bone formation around the implants in vivo. This article represents the first report on the two-staged, time-dependent antibacterial and osteogenesis effects of Ti-PHD, demonstrating its potential for clinical applications to inhibit implant-associated infections. STATEMENT OF SIGNIFICANCE: The present study develops a two-staged time-dependent system for local dimethylaminododecyl methacrylate (DMADDM) delivery via Ti implant (referred to as Ti-PHD). DMADDM and hydroxyapatite (HA) are loaded on to the Ti surface with poly dopamine (PDA). Ti-PHD can release DMADDM during the high-risk period of infection in the first stage, and then promote osseointegration and new bone formation in the second stage. This bioactive and therapeutic Ti is promising to inhibit infections and enhance implant success.

KEYWORDS:

Animal model; Antibacterial; Bioactive and therapeutic; Dimethylaminododecyl methacrylate; Implant-related infections; Osseointegration

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