Abstract
Percutaneous devices are a key technology in clinical practice, used to connect internal organs to external medical devices. Examples include prosthesis, catheters and electrical drivelines. Percutaneous devices breach the skin’s natural barrier and create an entry point for pathogens, making device infections a widespread problem. Modification of the percutaneous implant surface to increase skin integration with the aim to reduce subsequent infection is attracting a great deal of attention. While novel surfaces have been tested in various in vitro models used to study skin integration around percutaneous devices, no skin model has been reported, for the study of bacterial infection around percutaneous devices. Here, we report the establishment of an in vitro human skin equivalent model for driveline infections caused by Staphylococcus aureus, the most common cause of driveline-related infections. Three types of mock drivelines manufactured using melt electrowriting (smooth or porous un-seeded and porous pre-seeded with human fibroblasts) were implanted in human skin constructs and challenged with S. aureus. Our results show a high and stable load of S. aureus in association with the skin surface and no signs of S. aureus-induced tissue damage. Furthermore, our results demonstrate that bacterial migration along the driveline surface occurs in micro-gaps caused by insufficient skin integration between the driveline and the surrounding skin consistent with clinical reports from explanted patient drivelines. Thus, the human skin-driveline infection model presented here provides a clinically-relevant and versatile experimental platform for testing novel device surfaces and infection therapeutics.
Highlights
Percutaneous devices are routinely used in medicine to connect internal organs to external medical devices or their components
Staphylococcus aureus is the leading cause of driveline infections (Koval and Stosor, 2019) and has been previously shown to remain confined to the outermost layer of the epidermis in an human skin equivalent (HSE) wound infection model (Shepherd et al, 2009). This makes it an ideal organism for studying driveline-specific infections in HSEs in vitro as it does not invade into deeper tissue, unlike the Gram-negative wound pathogen Pseudomonas aeruginosa (Shepherd et al, 2009), ensuring that any bacterial penetration can only occur via the driveline opening
S. aureus was recovered at 24 h post inoculation in similar numbers from both HSE groups, with an average of 1.2 × 107 colony forming units (CFU)/mL recovered from intact HSEs and 1.3 × 107 CFU/mL from HSEs implanted with the PCL driveline (Figure 3A)
Summary
Percutaneous devices are routinely used in medicine to connect internal organs to external medical devices or their components. VADs are a type of mechanical circulatory support used in heart failure therapy They are attached to the heart and assist the heart in generating sufficient output to ensure adequate end organ perfusion (Koval and Stosor, 2019). In the United States alone, a minimum of 2,500 patients are added to the patient registry for mechanical circulatory support in any given year (Kirklin et al, 2017). Percutaneous devices, such as drivelines, cross the skin through a surgical incision and disrupt the skin’s natural barrier creating an entry point for pathogens (von Recum, 1984). Infections around percutaneous devices are highly prevalent with recent studies reporting catheter infection rates to be in the range of 2–33% over the life of the device, depending on the type of catheter (Salwiczek et al, 2014)
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