Burst Release of Antibiotics Combined with Long-Term Release of Silver Targeting Implant-Associated Infections: Design, Characterization and in vitro Evaluation of Novel Implant Hybrid Surface.

Kai Borcherding,Karsten Thiel,Nicole Bormann,Britt Wildemann,Ingo Grunwald,Dennis Marx,Linda Gätjen,Dirk Salz,Uwe Specht

doi:10.3390/ma12233838

Abstract

Implant-associated infections represent a serious risk in human medicine and can lead to complications, revisions and in worst cases, amputations. To target these risks, the objective was to design a hybrid implant surface that allows a local burst release of antibiotics combined with long-term antimicrobial activity based on silver. The efficacy should be generated with simultaneous in vitro cytocompatibility. The investigations were performed on titanium K-wires and plates and gentamicin was selected as an illustrative antibiotic. A gentamicin depot (max 553 µg/cm2) was created on the surface using laser structuring. The antibiotic was released within 15 min in phosphate buffered saline (PBS) or agar medium. Metallic silver particles (4 µg/cm2) in a titanium dioxide layer were deposited using plasma vapor deposition (PVD). About 16% of the silver was released within 28 days in the agar medium. The local efficacy of the incorporated silver was demonstrated in a direct contact assay with a reduction of more than 99.99% (Escherichia coli). The local efficacy of the hybrid surface was confirmed in a zone of inhibition (ZOI) assay using Staphylococcus cohnii. The biocompatibility of the hybrid surface was proven using fibroblasts and osteoblasts as cell systems. The hybrid surface design seems to be promising as treatment of implant-associated infections, considering the achieved amount and release behavior of the active ingredients (gentamicin, silver). The generated in vitro results (efficacy, biocompatibility) proofed the concept. Further in vivo studies will be necessary translate the hybrid surface towards clinical applied research.

Highlights

Implant-associated infections [1] are still an unsolved problem in orthopedics, even when advanced materials and implants with local antibiotics are available [2]
It was possible to develop a laser structuring process that allows a reproducible loading of antibiotics in an implant surface, which creates a reservoir for an initial local antibiotic burst release after implantation
The prolonged lag phase for the PS K-wire could be due to differences in the surface topography that trigger bacterial adhesion and proliferation [36]. These results demonstrate the potential of the silver/titanium dioxide coating for the long-term prevention of bacterial colonization of the surface

Summary

Introduction

Implant-associated infections [1] are still an unsolved problem in orthopedics, even when advanced materials and implants with local antibiotics are available [2]. Materials 2019, 12, 3838 in the 1990s, the cost of the treatment for an implant-associated infection was five to seven and a half times higher than that of treatment without complications. The pathogens are Staphylococci [7], especially Staphylococcus aureus [8], which cause orthopedic bone implant infections. Local antibiotics have significantly more potential to prevent infections than systemically applied antibiotics, as shown in animals [9] and humans [2]. Local antibiotics enable high concentrations at the infection site that are not possible with systemic antibiotics and play a significant role against implant-associated infections [10]

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