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Our team’s design will not be subject to the problems associated with a complete coating. It includes an omniphobic coating on only the inside of the device, while leaving the outside as raw titanium alloy. With this design, the inside of the pump will be theoretically immune to thrombus. The outside of the pump will maintain its normal sintering to promote tissue ingrowth. No further ingrowth promotors will be added, as the pump is secured to the heart with a suture ring.

The most effective superomniphobic material found so far has been fluorinated nanotubes. These carbon nanotubes are affixed to a titanium surface at a 90 degree angle. They are then treated with F2 at a high temperature to become fluorinated. Single-walled nanotubes tend to be more expensive than multi-walled nanotubes.

Figure 6: Blood, Oil, and Water on Coated Ti-6Al-4V (reference 14) Figure 7: SEM Micrograph Fluorinated Carbon Nanotubes (reference 15)

The fluorinated nanotubes will be affixed to the inner walls of the inflow cannula. They will extend until the cessation of curvature on the outer lip. The area beyond this boundary will not be coated. The inside of the pump housing will be coated along with all surfaces of the impeller. Extra coating will be added to the sharp corners of the impeller, as many blood clots form preferentially in these locations. The outflow graft will also be coated in fluorinated nanotubes. This area may require a different method of tube fixation, as it is made of GoreTex® rather than titanium. The outflow graft coating will extend to the edge of the tube. Anticoagulant releasing sutures could prevent the boundary from clotting if warfarin is not an option.

JUSTIFICATION AND RATIONALE

Superomniphobic Coatings

Use of superomniphobic material for the coating of the left ventricular assist device was favorable over other hydrophobic options. This is because repulsion of protein along with water is critical for the success of the coating. Hydrophobicity can often be less favorable than hydrophilicity due to its inherent ability to attract the inner cores of protein. Therefore, any alternative methods of coating the left ventricular device would maintain omniphobicity. Repulsion of all blood occupying the pump at a given time could do more than stop protein adsorption. It could limit shear stress and possibly decrease the incidence of gastrointestinal bleeds. While fluorinated nanotubes are an attractive selection for a coating, there are alternatives that could potentially accomplish the same task. Polydimethylsiloxane polymers also exhibit omniphobic properties and may provide a more cost-effective solution. Application of the polymers may also be much easier than fixation of nanotubes. The surface of the titanium would theoretically need only purification and plasma etching. The coating could then be applied by dipping the device. Polydimethylsiloxane can maintain its properties for up to a year and is very cheap (reference 16). Another option is X-SLIPS, a waxy porous coating inspired by plants. X-SLIPS is also applied to surfaces by dipping and can be bound to many kinds of metals, plastics, glasses, and ceramics. It also boasts the added benefit of thermal self-repair. Under high heat stimulation, damage sustained by the coating can be remedied without physical or surgical intervention (reference 17). Thermal self-repair applies to even large areas of either physical or chemical damage. This property is beneficial, as explantation to repair or replace a device can be dangerous for the patient.

Figure 8: Polydimethylsiloxane Polymer Diagram (reference 16) Figure 9: X-SLIPS Origin and Function Flowchart (reference 17)

The main danger with these alternative coatings is the possibility of leaching. The surface could become eroded over time and toxic chemicals released into the bloodstream. All coatings would require in situ testing to determine chemical stability under bodily conditions. Currently, fluorinated nanotubes are considered the most eligible for use in implants. Their structure is inert and relatively durable. They also create the largest visually perceptible contact angle, which suggests that they are the most universally repellent. While they are the most expensive option, they would be applied to only the inside of the pump. Lesser surface area may offset large costs associated with this coating.

Cost Analysis

As mentioned previously, the cost of coating a left ventricular assist device will be largely determined by whether or not single-walled nanotubes are necessary for clotting immunity. The price difference between single-walled nanotubes and multi-walled nanotubes is very significant. Multi-walled nanotubes range from 2-30 dollars per gram whereas single walled nanotubes range from 156.25 to 300 dollars per gram: about a 90 percent difference (reference 18). Price of carbon fluorinated nanotubes may also change based on tube length and purity. Most tubes available for purchase currently have a purity of 99.5 percent. This level of purity may be excessive, or it may be lacking. Our blood coagulation tests will determine this. Tube length also varies significantly in most products. Some range from 2-10 microns. Others vary more. There is possibly an ideal length for optimal hemophobicity, which may require more expensive reagents. Unavailability of uniform tubes may necessitate production of tubes in the manufacturing process rather than purchase. A standardized procedure for acquiring and coating the LVADs with tubes on an industrial scale may decrease costs significantly (such that the price difference between coated and non-coated devices is negligible).

PROPOSED VERIFICATION TESTING

Mechanical Wear Testing

One of the most critical tests to perform on the nanotubes is mechanical testing. Many patients retain their devices for 10 years or more. Reoperation for replacement of worn parts is often not possible, as most LVAD recipients are in their final years of life. The tubes must maintain their position and endure constant fluid movement across their surfaces for years at a time. To ensure that no erosion occurs, a coated left ventricular assist device will be placed in different buckets of corrosive material and allowed to run for an extended period of time. At least one of the testing buckets will contain real or synthetic blood. Examination of the surface by scanning electron microscopy will occur at the conclusion of the mechanical tests. Length, thickness and topography will be analyzed on the coated surfaces of the device. The media contained in each bucket will be analyzed for trace amounts of nanotube.

Cytotoxicity Testing

Our device will be tested for cytotoxicity. Small samples of titanium will be coated in carbon fluorinated nanotubes and placed in cell culture. Cells cultured in the presence of the titanium may include blood cells, cardiac cells, human embryonic kidney cells, fibroblasts, neurons, and E. coli. Cultures will be studied and analyzed for slowed growth, inhibited cellular processes, and apoptosis. In addition to direct contact, a MEM elution assay will be performed to exaggerate the conditions found in the body. 0% relative cytotoxicity must be achieved before implantation, as long-term cell death could be devastating.

Implantation Testing

To truly test the long-term viability of our coating, implant testing is necessary. The devices will be implanted into pigs. These implants will be left in for 1.5 years, as most thrombus events occur in the first year. Monthly blood samples will be extracted from the animals to test for trace amounts of fluorine. At the conclusion of the testing period, the implants will be extracted and analyzed in a similar fashion to our mechanical wear tests. Any clots will be recorded.

Mechanical Coagulation Testing

The final tests that must be performed on the carbon fluorinated nanotubes are coagulation tests. The most relevant clotting test for this situation is a mechanical test. Blood is poured into a cup. A second cup is nested inside of the first, effectively sandwiching the blood. A force sensing device then spins one cup while leaving the other stationary. As the blood clots over time, turning requires more force. This force is documented and used to analyze how quickly coagulation occurs. We will use a similar device, however our cups will be coated in carbon fluorinated nanotubes. No blood clotting should be visible on the sides of the cups. The force required to rotate should remain constant for an extended period of time.

Sterilization

Because left ventricular assist devices are implanted in one of the most vulnerable parts of the human body, a rigorous sterilization process is critical. We will run sterilization tests on our devices. Similarly to the mechanical wear test, we will treat the coated LVAD to standard sterile procedures and then view the surface using scanning electron microscopy. Any wear or denaturation inflicted on the tubes must be addressed. High temperatures can temporarily rearrange unbound carbon nanotubes, however the properties of bound carbon nanotubes have not been entirely determined yet. Fortunately, sterile procedures can be adapted. If high temperatures are damaging, chemical sterilization may also be feasible. Surface observation will be performed after all possible protocols.