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J Mol Eng Mater. 2016 Mar;4(1). pii: 1640005. doi: 10.1142/S2251237316400050. Epub 2016 Aug 22.

Controlling the Biomimetic Implant Interface: Modulating Antimicrobial Activity by Spacer Design.

Author information

1
Bioengineering Program, University of Kansas, 3135A Learned Hall, 1530 W 15th Street Lawrence, Kansas 66045, USA.
2
Bioengineering Research Center (BERC), University of Kansas, 3138 Learned Hall, 1530 W 15th Street Lawrence, Kansas 66045, USA, dmytro.khvostenko@ku.edu.
3
Department of Neurosurgery, University of Kansas Medical Center, 3901 Rainbow Boulevard Kansas City, Kansas 66160, USA, parnold@kumc.edu.
4
Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry of USC, The University of Southern California CSA 142, 2250 Alcazar Street Los Angeles, CA 90033, USA, mlsnead@usc.edu.
5
Mechanical Engineering Department and BERC, University of Kansas, 3138 Learned Hall, 1530 W 15th Street Lawrence, Kansas 66045, USA.

Abstract

Surgical site infection is a common cause of post-operative morbidity, often leading to implant loosening, ultimately requiring revision surgery, increased costs and worse surgical outcomes. Since implant failure starts at the implant surface, creating and controlling the bio-material interface will play a critical role in reducing infection while improving host cell-to-implant interaction. Here, we engineered a biomimetic interface based upon a chimeric peptide that incorporates a titanium binding peptide (TiBP) with an antimicrobial peptide (AMP) into a single molecule to direct binding to the implant surface and deliver an antimicrobial activity against S. mutans and S. epidermidis, two bacteria which are linked with clinical implant infections. To optimize antimicrobial activity, we investigated the design of the spacer domain separating the two functional domains of the chimeric peptide. Lengthening and changing the amino acid composition of the spacer resulted in an improvement of minimum inhibitory concentration by a three-fold against S. mutans. Surfaces coated with the chimeric peptide reduced dramatically the number of bacteria, with up to a nine-fold reduction for S. mutans and a 48-fold reduction for S. epidermidis. Ab initio predictions of antimicrobial activity based on structural features were confirmed. Host cell attachment and viability at the biomimetic interface were also improved compared to the untreated implant surface. Biomimetic interfaces formed with this chimeric peptide offer interminable potential by coupling antimicrobial and improved host cell responses to implantable titanium materials, and this peptide based approach can be extended to various biomaterials surfaces.

KEYWORDS:

Infections; antimicrobial peptides; bio-nanomaterial; biocoating; implants; interface; peptide design; structural analysis

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