ISO 10993-4 in vivo thrombogenicity testing is frequently performed for regulatory approval of many blood-contacting medical devices and is often a key part of submission packages. Given the current state of in vivo thrombogenicity assays, a more robust and reproducible assay design, including in vitro models, is needed. This study describes an in vitro assay that integrates freshly harvested ovine blood containing minimal heparin in a closed pumped loop. To confirm the reproducibility of this assay, control materials were identified that elicited either a positive or a negative thrombogenic response. These controls demonstrated reproducibility in the resulting thrombogenicity scores with median scores of 5 and 0 for the positive and negative controls, respectively, which also demonstrated a significant difference (p < 0.0001). For a direct comparison of the in vitro blood loop assay to the traditional in vivo nonanticoagulated venous implant (NAVI) assay, seven sheep were used as blood donors for the loop and then as subjects for an NAVI assay. In each assay—loop or NAVI—three study articles were used: the positive and negative controls and a marketed, approved catheter. The resulting thrombogenicity scores were similar when comparing the loop to the NAVI results. For each study article, the median thrombogenicity scores were the same in these two different assays, being 0, 1, and 5 for the negative control, the marketed catheter, and the positive control, respectively. These data suggest that the in vitro assay performs similarly to the in vivo NAVI assay. This in vitro blood loop method has the potential to predict a materials' in vivo thrombogenicity, can substantially de-risk the materials or coating selection process, and may eventually be able to replace the in vivo models currently in use.

Tantalum (Ta) and its alloys have been used for various cardiovascular, orthopedic, fracture fixation, dental, and spinal fusion implants. This review evaluates the biological and material properties of Ta and its alloys. Specifically, the biological properties including hemocompatibility and osseointegration, and material properties including radiopacity, MRI compatibility, corrosion resistance, surface characteristics, semiconductivity, and mechanical properties are covered. This review highlights how the material properties of Ta and its alloys contribute to its excellent biological properties for use in implants and medical devices.

Nitinol (NiTi), a nickel–titanium alloy, has been used for various cardiovascular, orthopedic, fracture fixation, and orthodontic devices. As with most other metallic biomaterials, the corrosion resistance and biocompatibility of NiTi are primarily determined by the properties of the surface oxide layer such as thickness, chemical composition, structure, uniformity, and stability. Currently, a number of finishing methods are used to improve the properties of surface oxide of NiTi with an ultimate goal to produce a defect‐free, impurity‐free, thin homogeneous oxide layer that is stable and composed of only titanium dioxide (TiO2) with negligible amount of Ni species. This review discusses the effects of various surface finishing methods such as mechanical polishing, electropolishing, magnetoelectropolishing, heat treatments at different temperatures, passivation, chemical etching, boiling in water, hydrogen peroxide treatment, and sterilization techniques (steam autoclave, ethylene oxide, dry heat, peracetic acid, and plasma‐based treatments) on the properties of a surface oxide layer and how it impacts the corrosion resistance of NiTi. Considering the findings of the literature review, a checklist has been provided to assist with choosing finishing/sterilization methods and relevant rationale and recommendations to consider when selecting a surface finishing process for NiTi used in implantable medical devices.

Most blood-contacting medical devices must be assessed for potential thrombogenicity prior to regulatory approval. A common assay for screening and qualifying devices involves monitoring the reduction of platelet and leukocyte (P&L) counts in whole blood exposed to the device. We have validated an improved method for assessing a device's effect on platelet activation and surface adhesion, offering significant improvement over the current ASTM F2888-13 method, which uses blood fully anticoagulated by acidified citrate (known to significantly inhibit platelet responsiveness). Our method uses minimal heparinization (final concentration 1 IU/mL) to optimize the response to commonly used control materials: latex, black rubber, and high-density polyethylene (HDPE). We also have shown the assay's capacity to appropriately assess a legally marketed comparator device (LMCD) with a documented clinical history. The test materials were prepared for incubation and allowed to remain in contact with the citrated or heparinized blood for ∼1 h at 37 °C. A complete blood count was performed prior to exposure, and at the end of the incubation period, reductions in P&L counts were recorded. Results from citrate-anticoagulated assay showed only a marginal response to the positive control, black rubber. Using heparinized blood, the assay generated a robust response to the positive controls, the “intermediate scoring” controls, and also assessed a legally marketed and approved device as clearly nonthrombogenic. This modification adds robustness and sensitivity to this quick and inexpensive thrombogenicity assay and should be incorporated into the next ASTM standards.