Antibacterial and immunogenic behavior of silver coatings on additively manufactured porous titanium

Journal article (2018)

Authors

M. Croes University Medical Center Utrecht

S. Bakhshandeh University Medical Center Utrecht

C. H.E. Boel University Medical Center Utrecht

Jacqueline Alblas University Medical Center Utrecht

Amir A. Zadpoor Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

A. A. Zadpoor Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

Amir Abbas Zadpoor Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

A.A. Zadpoor Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

Harrie Weinans University Medical Center Utrecht, Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

HH Weinans University Medical Center Utrecht, Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

H. Weinans University Medical Center Utrecht, Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

S. Amin Yavari University Medical Center Utrecht

I.A.J. van Hengel Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

I. A.J. van Hengel Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

Ingmar A.J. van Hengel Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering

K. Lietaert Katholieke Universiteit Leuven, 3D Systems – LayerWise NV

Kok van Kessel University Medical Center Utrecht

B. Pouran Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering , University Medical Center Utrecht

Bart C.H. van der Wal University Medical Center Utrecht

H. C. Vogely University Medical Center Utrecht

Wouter Van Hecke University Medical Center Utrecht

A. C. Fluit University Medical Center Utrecht

Research Group

Biomaterials & Tissue Biomechanics (Mechanical, Maritime and Materials Engineering) (TU Delft)

Additive manufacturing Porous implants Hydrogels Anti-bacterial coatings Bone morphology Electrophoretic deposition Osteomyelitis Rat tibia model

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Published Date

2018

Language

English

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Faculty

Mechanical, Maritime and Materials Engineering

Department

Biomechanical Engineering

Research Group

Biomaterials & Tissue Biomechanics

Abstract

Implant-associated infections (IAI) are often recurrent, expensive to treat, and associated with high rates of morbidity, if not mortality. We biofunctionalized the surface of additively manufactured volume-porous titanium implants using electrophoretic deposition (EPD) as a way to eliminate the peri-operative bacterial load and prevent IAI. Chitosan-based (Ch) coatings were incorporated with different concentrations of silver (Ag) nanoparticles or vancomycin. A full-scale in vitro and in vivo study was then performed to evaluate the antibacterial, immunogenic, and osteogenic activity of the developed implants. In vitro, Ch + vancomycin or Ch + Ag coatings completely eliminated, or reduced the number of planktonic and adherent Staphylococcus aureus by up to 4 orders of magnitude, respectively. In an in vivo tibia intramedullary implant model, Ch + Ag coatings caused no adverse immune or bone response under aseptic conditions. Following Staphylococcus aureus inoculation, Ch + vancomycin coatings reduced the implant infection rate as compared to chitosan-only coatings. Ch + Ag implants did not demonstrate antibacterial effects in vivo and even aggravated infection-mediated bone remodeling including increased osteoclast formation and inflammation-induced new bone formation. As an explanation for the poor antibacterial activity of Ch + Ag implants, it was found that antibacterial Ag concentrations were cytotoxic for neutrophils, and that non-toxic Ag concentrations diminished their phagocytic activity. This study shows the potential of EPD coating to biofunctionalize porous titanium implants with different antibacterial agents. Using this method, Ag-based coatings seem inferior to antibiotic coatings, as their adverse effects on the normal immune response could cancel the direct antibacterial effects of Ag nanoparticles. Statement of Significance: Implant-associated infections (IAI) are a clinical, societal, and economical burden. Surface biofunctionalization approaches can render complex metal implants with strong local antibacterial action. The antibacterial effects of inorganic materials such as silver nanoparticles (Ag NPs) are often highlighted under very confined conditions in vitro. As a novelty, this study also reports the antibacterial, immunogenic, and osteogenic activity of Ag NP-coated additively-manufactured titanium in vivo. Importantly, it was found that the developed coatings could impair the normal function of neutrophils, the most important phagocytic cells protecting us from IAI. Not surprisingly, the Ag NP-based coatings were outperformed by an antibiotic-based coating. This emphasizes the importance of also targeting implant immune-modulatory functions in future coating strategies against IAI.