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In vitro methodology for medical device material thrombogenicity assessments: A use condition and bioanalytical proof-of-concept approach.

ABSTRACT: Device manufacturers and regulatory agencies currently utilize expensive and often inconclusive in vivo vascular implant models to assess implant material thrombogenicity. We report an in vitro thrombogenicity assessment methodology where test materials (polyethylene, Elasthane™ 80A polyurethane, Pebax®), alongside positive (borosilicate glass) and negative (no material) controls, were exposed to fresh human blood, with attention to common blood-contact use conditions and the variables: material (M), material surface modification (SM) with heparin, model (Mo), time (T), blood donor (D), exposure ratio (ER; cm² material/ml blood), heparin anticoagulation (H), and blood draw/fill technique (DT). Two models were used: (1) a gentle-agitation test tube model and (2) a pulsatile flow closed-loop model. Thrombogenicity measurements included thrombin generation (thrombin-antithrombin complex [TAT] and human prothrombin fragment F1.2), platelet activation (?-thromboglobulin), and platelet counts. We report that: (a) thrombogenicity was strongly dependent (p ?.05) on Mo, SM, and D (b) differences between positive control, test, and negative control materials became less pronounced as H increased from 0.6 to 2.0 U/ml, and (c) in vitro-to-in vivo case comparisons showed consistency in thrombogenicity rankings on materials classified to be of low, moderate, and high concern. In vitro methods using fresh human blood are therefore scientifically sound and cost effective compared to in vivo methods for screening intravascular materials and devices for thrombogenicity.

SUBMITTER: Wolf MF

PROVIDER: S-EPMC7821245 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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In vitro methodology for medical device material thrombogenicity assessments: A use condition and bioanalytical proof-of-concept approach.

Wolf Michael F MF Girdhar Gaurav G Anderson Arielle A AA Ubl Samantha R SR Thinamany Sinduja S Jeffers Hannah N HN DeRusha Courtney E CE Rodriguez-Fernandez Jenny J Hoffmann Sebastian S Strief Carrie A CA

Journal of biomedical materials research. Part B, Applied biomaterials 20200914 3

Device manufacturers and regulatory agencies currently utilize expensive and often inconclusive in vivo vascular implant models to assess implant material thrombogenicity. We report an in vitro thrombogenicity assessment methodology where test materials (polyethylene, Elasthane™ 80A polyurethane, Pebax®), alongside positive (borosilicate glass) and negative (no material) controls, were exposed to fresh human blood, with attention to common blood-contact use conditions and the variables: material ...[more]

PMID: 32929881

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Dataset Information

In vitro methodology for medical device material thrombogenicity assessments: A use condition and bioanalytical proof-of-concept approach.

Publications

In vitro methodology for medical device material thrombogenicity assessments: A use condition and bioanalytical proof-of-concept approach.

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