@article{f83aa3019c6a43a7899a5974128e6f09,
title = "Anti-infective characteristics of a new Carbothane ventricular assist device driveline",
abstract = "Objectives: Driveline infections are a major complication of ventricular assist device (VAD) therapy. A newly introduced Carbothane driveline has preliminarily demonstrated anti-infective potential against driveline infections. This study aimed to comprehensively assess the anti-biofilm capability of the Carbothane driveline and explore its physicochemical characteristics. Methods: We assessed the Carbothane driveline against biofilm formation of leading microorganisms causing VAD driveline infections, including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans, using novel in vitro biofilm assays mimicking different infection micro-environments. The importance of physicochemical properties of the Carbothane driveline in microorganism-device interactions were analyzed, particularly focusing on the surface chemistry. The role of micro-gaps in driveline tunnels on biofilm migration was also examined. Results: All organisms were able to attach to the smooth and velour sections of the Carbothane driveline. Early microbial adherence, at least for S. aureus and S. epidermidis, did not proceed to the formation of mature biofilms in a drip-flow biofilm reactor mimicking the driveline exit site environment. The presence of a driveline tunnel however, promoted staphylococcal biofilm formation on the Carbothane driveline. Physicochemical analysis of the Carbothane driveline revealed surface characteristics that may have contributed to its anti-biofilm activity, such as the aliphatic nature of its surface. The presence of micro-gaps in the tunnel facilitated biofilm migration of the studied bacterial species. Conclusion: This study provides experimental evidence to support the anti-biofilm activity of the Carbothane driveline and uncovered specific physicochemical features that may explain its ability to inhibit biofilm formation.",
keywords = "Anti-infective, Biofilms, Carbothane, Surface chemistry, Ventricular assist device driveline",
author = "Yue Qu and David McGiffin and Sanchez, {Lina Duque} and Thomas Gengenbach and Chris Easton and Helmut Thissen and Peleg, {Anton Y.}",
note = "Funding Information: The application of mechanical circulatory support (MCS) such as contemporary ventricular assist devices (VADs) has been an important advance in the management of patients with end-stage heart disease [1,2]. The need for a driveline from the pump to the controller and power source confers a high risk for a VAD-associated infection [3]. There is a spectrum of VAD-associated infections ranging from VAD-specific infections such as driveline exit site infection, tunnel infection, pump pocket infection to VAD-related bloodstream infection, and it is likely that the driveline is responsible for the initiation and persistence of these infections [3]. The most common VAD-specific infections are driveline exit site and tunnel infections (Fig. S1) [3,4]. Current antimicrobial and/or surgical treatment strategies are suboptimal in curing driveline infections, highlighting the importance of infection prevention. Widely used preventative strategies include prophylactic peri-operative antimicrobials, diligent wound care and hygiene, and at the time of implantation, not allowing the velour section to project externally beyond the exit site [3]. The velour section of the driveline is designed to stabilize the driveline in the subcutaneous tissue tunnel and to promote tissue in-growth into the driveline. Despite the application of these anti-infective strategies, infections still occur at a substantial rate of 10–20% annually [5,6]. Very recently, we examined infected drivelines explanted from VAD patients undergoing heart transplant and found that biofilms had migrated long distances up the driveline, with micro-gaps within the driveline velour, implying incomplete tissue integration and a likely pathway for biofilms to spread [7].An adherence assay mimicking early-stage microorganism-driveline interactions at the driveline exit site was carried out using four microbial pathogens of VAD driveline infections. After 2-h of incubation, viable counts showed that both the smooth and velour sections of the driveline allowed adherence of all microorganisms, with P. aeruginosa attaching to both sections at a significantly greater density than the other species (Fig. 1A). Qualitative SEM supported the viable count results and showed that very few S. aureus, S. epidermidis and C. albicans cells adhered to both sections of the Carbothane driveline in the 2-h incubation period (Fig. 1B).It is a particularly interesting result that the Carbothane driveline did not support the translation of adherent staphylococcal cells to mature biofilms under a dynamic environment. Biofilm EPS is the major mediator for the formation of microcolony/macrocolony biofilms [28,29]. Our previous work using the Pellethane HVAD driveline and other biomedical materials confirmed that the staphylococcal strains selected for this study could readily produce biofilm EPS under similar environmental conditions [10]. We thus speculated that the specific surface chemistry of the Carbothane driveline, possibly the presence of aliphatic function groups or fluorine, might have allowed single staphylococcal cells to attach but prevented anchoring of the EPS and the build-up of mature biofilms. Our CLSM study provided visual evidence to support the lower capability of the new Carbothane, relative to the Pellethane material, to allow staphylococcal biofilm EPS to attach on its surface. The resistance of the Carbothane driveline to biofilm EPS deposition may result in reduced biofilm formation and less biofilm-related infections at the driveline exit site. In addition, partial bacterial killing upon contact with the surface was observed for the Carbothane driveline smooth section. This contact killing is possibly due to the presence of fluorine in the surface of the Carbothane material [30] but future work is required to systemically study the interaction between Carbothane driveline materials, staphylococci, and different biofilm EPS in a quantitative manner.Despite the anti-EPS-anchoring and antibacterial properties of the Carbothane material, the presence of a driveline tunnel was able to promote staphylococcal biofilm formation on the Carbothane driveline surface. Biofilm formation of Staphylococcus spp. within the driveline tunnel was supported by the presence of an interstitial space between the driveline and the tissue tunnel that might trap the produced EPS in a confined space, as well as micro-gaps in the velour. Beside microbial early adherence and biofilm formation, biofilm migration in the tissue tunnel is another concern as it is clinically associated with disease severity [7]. Limited biofilm migration at the driveline-tunnel interface was noticed when the tunnel was tightly sealed (this study and [10]). We have previously revealed the presence of micro-gaps at the driveline-tunnel interface in patients with a VAD and speculated that these micro-gaps facilitated biofilm migration in the driveline tunnel to deeper tissues [7]. Findings from this in vitro study validated our speculation of the role of micro-gaps in the spread of infections.This work was financially supported by a Medtronic External Research Program to YQ, DM, AP and HT.Dr. Yue Qu, Prof. David McGiffin, Dr. Helmut Thissen, and Prof. Anton Peleg received a Medtronic External Research Program that financially supported this study. Medtronic played no direct role in the design of the study, interpretation of the results, and writing-up the manuscript. Prof. David McGiffin is a proctor for Abbott-implantation of HeartMate III ventricular assist device.The authors thank Medtronic for funding support and Monash Micro Imaging and Monash Ramaciotti Cryo EM Facility for the assistance with microscopy. Funding Information: This work was financially supported by a Medtronic External Research Program to YQ, DM, AP and HT. Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = dec,
doi = "10.1016/j.bioflm.2023.100124",
language = "English",
volume = "5",
journal = "Biofilm",
issn = "2590-2075",
publisher = "Elsevier",
}