Hydrophilic coating risks for heparin

Heparin is a sulfated glycosaminoglycan used commonly in hydrophilic coatings because it is anti-thrombogenic. This means some forms of heparin can actively interfere with thrombin’s reaction with fibrinogen, which winds up inhibiting the formation of fibrin, the main ingredient in thrombus, or blood clot. The heparin molecule also makes for a pretty slippery surface when coated onto things. For this reason, heparin has been used as a hydrophilic coating in medical devices for nearly three decades.

Recently, I was in a meeting with a client that makes heparin-coated catheters, among other things, and I suggested to him that I could whip up a surface that has a combination of heparin and hyaluronic acid (HA). I did not really have a reason for the suggestion. It was more a brainstorm, thinking out loud, and I was portraying it as something I could do with my company’s technology platform. The answer I got was surprising. He wasn’t interested, but not because of the HA. He wanted to get rid of heparin!

When I pressed him for a reason, he mentioned that heparin is recently known to be a risk factor for infections when used in conjunction with in-dwelling catheters. Apparently, it is conducive to the growth of certain types of bacteria. So, I fired up PubMed and did a 5-minute search to see what this guy was talking about, and sure enough, I found articles like this one on the risk factors of systemic heparin usage. Granted, even according to that article, heparin was only a single factor, and not a main cause of infection, but I was still surprised to find that out, not being an expert in that literature.

Just thought I would pass it on….

Some sticking points with lubricity and durability testing

Testing the lubricity and durability of the hydrophilic coating on your medical device is probably one of the most important verification actions you will perform during development. Afterall, you need to prove that something is present on the surface that lowers friction. How?

For those that are new to this field, let me explain some basic methods used to determine lubricity and durability:

1) The Pinch Test — This is the most common test used for finding friction at the surface. The only company that I know of that sells these devices is Harland Medical, but you can also make one of your own, which is what I have seen most times. In a nutshell, this is a device that pinches a catheter, wire, or surface between two plates with a known amount of force, and then tries to pull the device through the plate. A mechanical analyzer measures the force it takes to pull the device through. From this, you can calculate static friction, dynamic friction, and coefficient of friction. If you pass the device through the pinch test multiple times, eventually the coating will fail and friction will skyrocket. This is how you measure durability, i.e. number of cycles to failure. Failure can be set arbitrarily as some % increase in friction.

2) The Tortuous Path Test — An older test, the tortuous path test, works by pulling a coated wire through a permanently installed catheter apparatus. The catheter is purposely configured to have several turns and angles which the test article must be pulled through. Once again, the test article is hooked up to a mechanical analyzer which measures the amount of force it takes to pull it through. Also, once again, this measures friction for lubricity, and multiple cycles measure durability. Usually this test is only done on guidewire samples, but it can be done with catheters if they have mandrels inserted within. That is not recommended, however.

3) Dragging a Weight — Another test involves coating a surface with the hydrophilic material and then dragging a weight across it while measuring the force it takes to drag the weight. This is a crude method, but it can yield results.

4) Pulling through a Hole — This test involves boring a hole through some kind of material, i.e. a piece of plastic, or even a piece of meat, and then pulling the coated device through the hole while measuring force. Again, this method can be considered crude, but it can also be consistent if done properly.

The biggest problem experienced with all of these methods is that the results are highly variable. They can vary from day to day, and it is of course impossible to compare between the different methods. They have not been correlated, and correlation is probably not even possible. Moreover…. and here’s the kicker…. they have never been correlated to real world durability. So, in effect, we really have no idea how a device’s performance in one of these tests equates with how well the device performs in vivo.

Another interesting thing to note is that your results can conflict between the different tests. If you coat 5 different types of guidewire and do a pinch test to get a ranking of lubricities, you might get a completely different order of ranking when you go to do a tortuous path test on the same groups of wires. Why?

The only explanation I have for this is that these tests all test different things. Even within the pinch tests, for example, you can have different parameters that would greatly affect your results. Are you pinching at a point? Or are you pinching between two plates that are 3 inches long? What are the plates made out of? Silicone will give you different results than acrylic! With the tortuous path test, you have a huge contact surface area, at multiple points along the entire device, which is way different than the concept of the pinch test. Plus you can have different materials for your tortuous path too, and different turn configurations.

The same concepts also apply to the other two tests I described. Namely, you can vary materials, dimensions, and other parameters in there too.

So what do you do if you are testing a device? My advice is pick one or two of these methods and stick with them. Keep things internally consistent. Do not try to compare to other test methods or devices or even tests done at different sessions. Take everything that you want to test, and test it all head-to-head in one sitting if you can.

Hyaluronic Acid Review

Some of the hydrophilic coatings out there, including Hydak are based on the glycosaminoglycan called hyaluronic acid, or hyaluronate. An article on the Glyco Forum gives an overview of hyaluronate research, which is valuable knowledge for understanding properties of coatings made from this material.

Click here for the article.