This week we learned about the importance of biocompatibility testing and how this testing assess the compatibility of medical devices with a biological system. This test must be done for a material or device before clinical studies can occur. Compare and contrast at least three different biocompatibility testing techniques between vivo or vitro experiments. What similarities does microorganisms and animals or humans both have to encounter before clinical examinations and what differences occur?
Some biocompatibility testing techniques that could occur to assess the compatibility of medical devices with a biological system include cytotoxicity, genotoxicity, and toxicokinetics. Cytotoxicity is checking to see if cell death is present when exposed to the device. Genotoxicity is checking to see if the device is adversely affecting the genetic makeup of the organism (genetic mutations rise when device is present). Toxicokinetics looks at the by-products that may be present when a materials or device degrades or is absorbed into the body and what those by-products go off and do in the body later (harmful? cause other ailments?). In the diagram from the ISO 10993-1 Test Matrix, all three of these biocompatibility testing techniques are listed. Cytotoxicity is a standard ISO evaluation test for all body contact-related surfaces, while Genotoxicity is a standard ISO evaluation test for just permanent mucosal membrane, permanent breached or compromised surfaces, permanent indirect blood paths, prolonged and permanent tissue/bone/dentin communicating, prolonged and permanent circulating blood, prolonged and permanent tissue/bone, prolonged and permanent blood contact. Toxicokinetics is not listed in the ISO 10993-1 Test Matrix.
Going off of what @Sandra-Raju said, other tests can include hemocompatibility, implantation, pharmacokinetics. Hemocompatibility looks into how blood reacts when interacting with the device. This is important to know whether blood would coagulate around the device or would blood continue flowing like normal. Implantation investigates how the body reacts when the device is implanted into the body. For example, with breast implants silicon molecules can pass through the fibrous capsule layer that forms around the implant which can lead to synovial metaplasias which are an immune response due to the implantation. There are times when we want to induce an immune response upon implantation but then there are times where it is not beneficial. Additionally, it is important to check the duration of the inflammation of whether it is short term or chronic. Lastly, pharmacokinetics is the testing that looks at the reaction of the body with certain molecules that can be in drugs or biologics. There’s a specific list of testing that fall under pharmacokinetics which include absorption (understanding how the body absorbs the molecule), distribution (how the molecule is spread throughout the body), metabolism (how the body breaks down the molecule), excretion (how the body gets rid of the molecule). This list can be condensed into ADME testing. With all these tests mentioned, it should be seen that in vitro tests will predict exactly how in vivo testing results would occur. If an in vitro test shows that blood is not coagulating around the device then you would expect the same to occur in vivo. This thought process can be applied to all the tests including the ones @Sandra-Raju mentioned as well.
The biocompatibility testing I looked at were hemocompatibility, carcinogenicity and chronic toxicity testing. Hemocompatibility includes many tests, such as hemolysis testing, complement activation testing, in vivo thrombogenicity testing. For the latter option, this test determines the thrombo-resistance of the device and whether or not it activates platelets, forms a thrombus, evokes embolism or injures the cells. Carcinogenicity testing or tumorigenicity testing determines the devices' potential to form a tumor. There is currently a transgenic mouse assay(in vivo) that is being researched as it is generally faster the the previous two mouse lifetime assay. Chronic toxicity tests are initially tests where a species is exposed to a target substance for repeated intervals throughout long periods of time to determines their toxicity over the life span of the species. Carcinogenicity testing is somewhat similar in that regard. According to the ISO 10993-1 Test matrix both the carcinogenicity and hemocompatibility tests are mostly only utilized for implant and external communicating devices. Chronic toxicity however can be applied to surface devices.
Some interesting biocompatibility tests I found are sensitization assays, irritation tests, and subchronic toxicity testing. Sensitization assays are tests done to show any adverse effects a certain material can have if exposed to a tissue for a long time. Most sensitization testing is in vivo and they mostly utilize Guinea pigs for patch testing. This is when a bare patch of skin has prolonged exposure to the material. Irritation tests evaluate the degree of local irritation when biologic tissue is exposed to a medical device. This is another test that mostly has in vivo animal studies. If a medical device will be interacting with any internal systems or fluid, an intracutaneous test is usually done which includes injecting extracts of the material through the skin. This is accurate since the test has either the same conditions as the device would be in use, or provide a worse condition. In this way, it can reliably determine whether there are any worrying elements that may cause irritation. This is different from sensitization tests in that sensitivity is caused by a body's immune response to the material while irritation consists of symptoms that are directly caused by the device itself. Subchronic toxicity tests are tests that determine harmful effects from medical devices with a long exposure time. The exposure time, unlike in sensitization assays, is specifically defined as being up to 10% of the total lifespan of the animal. Unlike sensitization tests, these tests are particularly meant to mimic the use conditions of permanent implants such as hip replacements, knee replacements, and more. Sensitization assays are meant to evaluate the body's immune response to a foreign material over a long period of time, but subchronic toxicity is meant to evaluate any toxic effects a foreign material might have over a long period of time.
Some biocompatibility testing techniques include cytotoxicity testing, hemocompatibility testing, and implantation testing. All of these testing methods can be conducted either in vitro or in vivo. Cytotoxicity testing tests the toxic effects of a material on cultured cells for in vitro methods. As for in vivo, one would test the toxic effects of a material in either animals or humans. For hemocompatibility tests, this asses how the material interacts with blood components, such as coagulation or hemolysis (destruction of red blood cells). This test can also occur in vitro (testing in cells) or in vivo (testing in animal models). Lastly, implantation testing tests how the material responds to the tissue environment either in cells (in vitro) or in animal models (in vivo). In all of these types of tests, the in vitro methods provide answers regarding a limited environment. Meaning, that in vitro methods only provide answers to how a material responds to only that particular cultured cell. On the other hand, in vivo, tests are able to provide a broader insight on how the material is responding to the entire human system rather than a concentrated environment. However, when it comes to in vivo testing, there are more rigorous ethical concerns and laws that researchers would need to navigate through, unlike in vitro testing.