Clinical Features of Device-Associated Infections

The uses of implantable medical devices are safer and more common since sterilization methods and techniques were established a century ago; however, device-associated infections (DAIs) are still frequent and becoming a leading complication as the number of medical device implantations keeps increasing. This urges the world to develop instructive prevention and treatment strategies for DAIs, producing a publication boom on the design of antibacterial surfaces for implantable medical devices. To help identify the flaws of our current antibacterial designs and advance their clinical translations, the clinical features of DAIs are recently highlighted by Huiliang Cao et al [1].

Biomaterials;Antibacterial surface;Implantable medical devices;Titanium;Biocompatibility

1. Introduction

It was estimated that over 500,000 types of medical devices, such as dental implants, vascular graft/endograft, orthopedic prosthetics, catheters, etc., are currently marketing globally for medical applications [1]. Every year, there are about 10,000,000 dental implants and more than 1,000,000 cardiovascular electronic devices inserted around the world [2][3]. It has been estimated that 100 million urinary catheters are sold worldwide each year [4]. As the population of the aged increases, procedures for implantable medical devices are expected to increase rapidly in the coming years. In the United States of America (USA), the primary total knee arthroplasty (TKA) is going to grow by 85%, to 1.26 million procedures by 2030 [5]. In Germany, by 2040, the total number of TKA is expected to increase by 45% to over 244,000 procedures; and the incidence rate of total hip arthroplasty (THA) is projected to increase to 437 per 100,000 inhabitants [6]. In the United Kingdom, the volume of hip and knee joint replacement is expected to increase by almost 40% by 2060 [7]. Bacterial infections are one of the most frequent and severe complications associated with the clinical application of implantable medical devices [1]. It was reported that device-associated infections (DAIs), including ventilator-associated pneumonia, catheter-associated urinary tract infection, and central-catheter-associated bloodstream infection), accounted for approximately 26% of all healthcare-associated infections (HAIs) in the USA [8]. The annual number of HAIs in European Union countries is about 3.2 million, including 37,000 registered mortalities [9]. The financial burden for the treatment of a DAI is also extraordinarily high. For instance, the average revision costs in the USA for infected hip and knee arthroplasty were approximately USD 80 and 60 thousand, respectively [10]. Additionally, by 2030, the estimated combined annual hospital costs related to arthroplasty infection will rise to USD 1.85 billion in the USA alone [11]. This urges the world to develop instructive prevention and treatment strategies for DAIs.
Accordingly, fundamental research on the development of various antibacterial surfaces has dramatically increased in recent years. Screening for “

antibacterial surface1. Site-specific Incidence” or “antibacterial coating” in the topic of the articles included in the Web of Science (www.webofscience.com; accessed on 14 February 2022) can hit more than 50,000 records between the years 1996 and 2021. Around 80% of these records were published during the last decade (between 2012 and 2021), and over 67% of them were published during the last five years (between 2017 and 2021), identifying a boom in developing antibacterial surfaces or coatings. Developing antibacterial surfaces for implantable medical devices also is currently a hot direction among the Chinese communities focusing on biomaterials science and engineering. Typical designs published in the first half of 2022 include copper-bearing titanium [12], surface charge and wettability control in lysozyme [13], light-activatable carbon monoxide gas generation by triiron dodecacarbonyl loaded polydopamine [14], clickable peptide engineered surface [15], calcium-doped titanium targeting blood protein adsorption [16], puncture and ROS (reactive oxygen species) release by nanorod zinc oxide patterns [17], light-stimulated ROS generation by rare-earth elements-doped titanium dioxide coating [18], on-demand antibiotics release by responsive polymers [19][20], and bacteriophage-modified alginate hydrogels [21]. This trend demonstrates that the academic community has already realized the urgency of solving the DAI problem, whereas only a limited number of these innovations have entered clinical applications or clinical studies around the world. A very small number of registered records concerning antibacterial surfaces were found in ClinicalTrials.gov (accessed on 22 May 2022) by searching for “device infection” in the “Condition or disease” field. As shown in Table 1, silver in metallic or ionic forms is the most popular active ingredient in developing antibacterial medical devices. Currently, a handful of antibacterial surfaces have been branded for clinical uses, which are commonly silver-based and normally custom-made (available on request). These include Acticoat using magnetron sputtering synthesized nanosilver coatings for wound care [22], MUTARS prosthesis reducing infections by electroplating a metallic-silver surface, METS prosthesis acting against pathogenic bacteria by absorption of ionic silver to anodized titanium implants [23], PorAg prosthesis taking advantage of a controlled electrochemical reaction (do not directly release silver ions) in a titanium-silver alloy for disinfection [23], and PROtect nails administrating gentamicin for prevention of infections in complex open fractures [24]. These commercial promotions have set examples for the development of antibacterial surfaces for implantable medical devices; however, it is still a challenge to improve the quality and efficiency of translational research over those “antibacterial surface” or “antibacterial coating” reports.

Table 1. Antibacterial surface registered for clinical studies *.
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