The effect of ventricular assist device‐associated biomaterials on human blood leukocytes

Abstract

Ventricular assist devices (VADs) are an effective bridging or destination therapy for patients with advanced stage heart failure. These devices remain susceptible to adverse events including infection, bleeding, and thrombus; events linked to the foreign body response. Therefore, the biocompatibility of all biomaterials used is crucial to the success of medical devices. Biomaterials common in VADs-DLC: diamond-like carbon coated stainless steel; Sap: single-crystal sapphire; SiN: silicon nitride; Ti: titanium alloy; and ZTA: zirconia-toughened alumina-were tested for their biocompatibility through incubation with whole human blood for 2 h with mild agitation. Blood was then removed and used for: complete cell counts; leukocyte activation and death, and the production of key inflammatory cytokines. All were compared to time 0 and an un-exposed 2 h sample. Monocyte numbers were lower after exposure to DLC, SiN, and ZTA and monocytes showed evidence of activation with DLC, Sap, and SiN. Neutrophils and lymphocytes were unaffected. This approach allows comprehensive analysis of the potential blood damaging effects of biomaterials. Monocyte activation by DLC, Sap, ZTA, and SiN warrants further investigation linking effects on this cell type to unfavorable inflammatory/thrombogenic responses to VADs and other blood handling devices. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1730-1738, 2018.

Artificial shear stress effects on leukocytes at a biomaterial interface

“… While this level of shear is neither stagnant (<50 −100 s –1 ) resulting in thrombosis, nor significantly high enough to cause cell damage (≳5000 s –1 ), it is a mid‐range level of shear that causes leukocyte activation which contributes to thrombus formation. Also, surface roughness of the discs was monitored with order of roughness from highest to lowest of DLC > Ti > Sap.…”

“…Results from neutrophils and monocytes without shear were consistent with previous results exposing these biomaterials to blood in a static environment. CD11b Bright expression on monocytes increased significantly in all samples apart from those in contact with DLC without shear (Figure E). Cell death was unchanged for both neutrophils and monocytes (Figure C and F).…”

“…Our previous work showed that Sap causes higher levels of leukocyte activation than the other biomaterials studied and the rheometer model demonstrates that these are likely exacerbated by shearing. This could pose a problem for VAD developers as single‐crystal sapphire is considered for VAD bearings, an area of very high shear and prone to thrombus generation.…”

“…Finally, cytokine response to a commonly used prototypic inflammatory stimuli—LPS—was considered. Instead of simply measuring the same cytokines as previously or used by other investigators, an array approach was used first to better identify candidates for further analysis. IL‐1α is an IL‐1 family member that interacts with the IL‐1 receptor to produce a pro‐inflammatory response.…”

“…Biomaterial discs were prepared for use and surface area and surface roughness were measured as per the previous study. The order of roughness from highest to lowest was DLC (Ra = 0.774 μm) > Ti (Ra = 0.099 μm) > Sap (Ra = 0.044 μm).…”