Abstract

Bacterial biofilm on medical devices is difficult to eradicate. Many have capitalized the anti-infective capability of silver ions (Ag+) by incorporating nano-silver (nAg) in a biodegradable coating, which is then laid on polymeric medical devices. However, such coating can be subjected to premature dissolution, particularly in harsh diseased tissue microenvironment, leading to rapid nAg clearance. It stands to reason that impregnating nAg directly onto the device, at the surface, is a more ideal solution. We tested this concept for a corneal prosthesis by immobilizing nAg and nano-hydroxyapatite (nHAp) on poly(methyl methacrylate), and tested its biocompatibility with human stromal cells and antimicrobial performance against biofilm-forming pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Three different dual-functionalized substrates—high Ag (referred to as 75:25 HAp:Ag); intermediate Ag (95:5 HAp:Ag); and low Ag (99:1 HAp:Ag) were studied. The 75:25 HAp:Ag was effective in inhibiting biofilm formation, but was cytotoxic. The 95:5 HAp:Ag showed the best selectivity among the three substrates; it prevented biofilm formation of both pathogens and had excellent biocompatibility. The coating was also effective in eliminating non-adherent bacteria in the culture media. However, a 28-day incubation in artificial tear fluid revealed a ~40% reduction in Ag+ release, compared to freshly-coated substrates. The reduction affected the inhibition of S. aureus growth, but not the P. aeruginosa. Our findings suggest that Ag+ released from surface-immobilized nAg diminishes over time and becomes less effective in suppressing biofilm formation of Gram-positive bacteria, such as S. aureus. This advocates the coating, more as a protection against perioperative and early postoperative infections, and less as a long-term preventive solution.

Highlights

  • Biofilm formation is initiated when planktonic bacterial cells attach on, multiply, and form a community of microorganisms on living and non-living surfaces, e.g., on the surface of water pipes, Pathogens 2019, 8, 93; doi:10.3390/pathogens8030093 www.mdpi.com/journal/pathogensPathogens 2019, 8, 93 rocks, teeth, cornea, and implanted medical devices [1]

  • Medical devices have played an essential role in improving and advancing the healthcare system, including the use of KPros in providing vision to patients with severe corneal diseases and to patients that suffer from multiple donor graft rejection [25]

  • Cases of antibioticresistant bacterial infections, which are normally caused by the attachment of bacteria and subsequent formation of biofilm on the medical devices, have been a critical issue for clinicians and patients [26]

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Summary

Introduction

Biofilm formation is initiated when planktonic bacterial cells attach on, multiply, and form a community of microorganisms on living and non-living surfaces, e.g., on the surface of water pipes, Pathogens 2019, 8, 93; doi:10.3390/pathogens8030093 www.mdpi.com/journal/pathogensPathogens 2019, 8, 93 rocks, teeth, cornea, and implanted medical devices [1]. Medical devices are susceptible to bacterial adherence and biofilm formation, especially those that extend from a sterile environment (e.g., blood or anterior chamber) to the surface of the body (e.g., skin or ocular surface), such as cardiac ventricular assist devices or corneal prosthetic devices (KPros). Patients treated with this type of medical devices require life-long antibiotic treatment, subjecting them to the risk of developing antibiotic-resistant infections [2]. The infected device has a high tendency to fail and eventually requires removal and replacement in order to control and eradicate the infection

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