Platelet and leukocyte count assay for thrombogenicity screening of biomaterials and medical devices: Evaluation and improvement of <scp>ASTM F2888</scp> test standard

Lu, Qijin; Nehrer, Joshua M; Li, Jiaming; Jamiolkowski, Megan A.; Rinaldi, Jean E.; Malinauskas, Richard A.

doi:10.1002/jbm.b.34887

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…57,58 A significant decrease in the number of individual platelets suspended in PRP after exposure to a biomaterial can be indicative of significant platelet adhesion on the biomaterial surface, formation of platelet aggregates, and/or platelet entrapment in thrombi. [57][58][59] As seen in Figure 7A, PRP exposed to the positive control, Buna-N rubber, demonstrated statistically significant decrease in These results are consistent with previous studies on surface modified titanium with nanoscale topography. For example, Park et al…”

Section: In Vitro Human Platelet Responses To Nanostructured Titanium...supporting

confidence: 87%

“…Platelet count is an in vitro assessment of a biomaterial's ability to induce platelet activation and thrombus formation 57,58 . A significant decrease in the number of individual platelets suspended in PRP after exposure to a biomaterial can be indicative of significant platelet adhesion on the biomaterial surface, formation of platelet aggregates, and/or platelet entrapment in thrombi 57–59 …”

Section: Resultsmentioning

confidence: 99%

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Influence of titanium nanoscale surface roughness on fibrinogen and albumin protein adsorption kinetics and platelet responses

Boehm,

Skoog,

Diaz‐Diestra

et al. 2023

J Biomedical Materials Res

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Biomaterials with nanoscale topography have been increasingly investigated for medical device applications to improve tissue–material interactions. This study assessed the impact of nanoengineered titanium surface domain sizes on early biological responses that can significantly affect tissue interactions. Nanostructured titanium coatings with distinct nanoscale surface roughness were deposited on quartz crystal microbalance with dissipation (QCM‐D) sensors by physical vapor deposition. Physico‐chemical characterization was conducted to assess nanoscale surface roughness, nano‐topographical morphology, wettability, and atomic composition. The results demonstrated increased projected surface area and hydrophilicity with increasing nanoscale surface roughness. The adsorption properties of albumin and fibrinogen, two major plasma proteins that readily encounter implanted surfaces, on the nanostructured surfaces were measured using QCM‐D. Significant differences in the amounts and viscoelastic properties of adsorbed proteins were observed, dependent on the surface roughness, protein type, protein concentration, and protein binding affinity. The impact of protein adsorption on subsequent biological responses was also examined using qualitative and quantitative in vitro evaluation of human platelet adhesion, aggregation, and activation. Qualitative platelet morphology assessment indicated increased platelet activation/aggregation on titanium surfaces with increased roughness. These data suggest that nanoscale differences in titanium surface roughness influence biological responses that may affect implant integration.

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Section: In Vitro Human Platelet Responses To Nanostructured Titanium...supporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Influence of titanium nanoscale surface roughness on fibrinogen and albumin protein adsorption kinetics and platelet responses

Boehm,

Skoog,

Diaz‐Diestra

et al. 2023

J Biomedical Materials Res

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Molecular Biomarkers for In Vitro Thrombogenicity Assessment of Medical Device Materials

Patel,

Parrish,

Serna

et al. 2024

J Biomed Mater Res

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To develop standardized in vitro thrombogenicity test methods for evaluating medical device materials, three platelet activation biomarkers, beta‐thromboglobulin (β‐TG), platelet factor 4 (PF4), soluble p‐selectin (CD62P), and a plasma coagulation marker, thrombin–antithrombin complex (TAT), were investigated. Whole blood, drawn from six healthy human volunteers into Anticoagulant Citrate Dextrose Solution A was recalcified and heparinized over a concentration range of 0.5–1.5 U/mL. The blood was incubated with test materials with different thrombogenic potentials for 60 min at 37°C, using a 6 cm2/mL material surface area to blood volume ratio. After incubation, the blood platelet count was measured before centrifuging the blood to prepare platelet‐poor plasma (PPP) and platelet‐free plasma (PFP) for enzyme‐linked immunosorbent assay analysis of the biomarkers. The results show that all four markers effectively differentiated the materials with different thrombogenic potentials at heparin concentrations from 1.0 to 1.5 U/mL. When a donor‐specific heparin concentration (determined by activated clotting time) was used, the markers were able to differentiate materials consistently for blood from all the donors. Additionally, using PFP instead of PPP further improved the test method's ability to differentiate the thrombogenic materials from the negative control for β‐TG and TAT. Moreover, the platelet activation markers were able to detect reversible platelet activation induced by adenosine diphosphate (ADP). In summary, all three platelet activation markers (β‐TG, PF4, and CD62P) can distinguish thrombogenic potentials of different materials and detect ADP‐induced reversible platelet activation. Test consistency and sensitivity can be enhanced by using a donor‐specific heparin concentration and PFP. The same test conditions are applicable to the measurement of coagulation marker TAT.

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Alternative Anticoagulant Strategy to Improve the Test Sensitivity of ASTM F2888‐19 Standard for Platelet and Leukocyte Count Assay

Patel,

Serna,

Parrish

et al. 2024

J Biomed Mater Res

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The ASTM F2888‐19 standard for platelet and leukocyte count assay is the only standardized test method for assessing platelet and leukocyte interactions with blood‐contacting device materials. This study aimed to address two limitations of the ASTM F2888‐19 standard: low test sensitivity for leukocyte count and high test sample surface area to blood ratio (12 cm2/mL). Human blood from healthy adult donors was drawn into polypropylene tubes with either 3.2% sodium (Na) citrate or anticoagulant citrate dextrose solution A (ACDA). Immediately before starting the test, the blood was recalcified and heparinized to a concentration of 1, 1.5, or 2 U/mL and incubated with the test materials of varying thrombogenic potential at an exposure ratio of 6 or 12 cm2/mL for 1 h at 37°C ± 2°C in a shaking water bath. Complete blood count was measured using a hematology analyzer. The results show that both, Na‐citrated blood (6 or 12 cm2/mL exposure ratio) and ACDA blood (6 cm2/mL ratio), were able to differentiate thrombogenic materials from commonly used biomaterials based on platelet count changes. The magnitudes of difference between the thrombogenic materials and biomaterials depends on heparin concentration. The test sensitivity was highest when ACDA blood, heparinized to 1 U/mL heparin, was used. Moreover, the use of ACDA blood, unlike Na‐citrated blood, also allowed the assay to distinguish between the thrombogenic materials from commonly used biomaterials based on leukocyte count changes. In conclusion, the use of ACDA blood significantly increased test sensitivity of the ASTM F2888‐19 test method in differentiating materials with varying thrombogenicity based on both platelet and leukocyte counts, while reducing blood exposure ratio to 6 cm2/mL. These findings will be used to revise the ASTM F2888 standard in the future.

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Platelet and leukocyte count assay for thrombogenicity screening of biomaterials and medical devices: Evaluation and improvement of ASTM F2888 test standard

Cited by 4 publications

References 17 publications

Influence of titanium nanoscale surface roughness on fibrinogen and albumin protein adsorption kinetics and platelet responses

Influence of titanium nanoscale surface roughness on fibrinogen and albumin protein adsorption kinetics and platelet responses

Molecular Biomarkers for In Vitro Thrombogenicity Assessment of Medical Device Materials

Alternative Anticoagulant Strategy to Improve the Test Sensitivity of ASTM F2888‐19 Standard for Platelet and Leukocyte Count Assay

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