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It has been increasingly understood that the biocompatibility of an implanted device is a more subtle and detailed question than simply identifying the raw materials from which it is made. Biocompatibility is properly understood as a property of a finished device, including the design and intended use, the raw materials, manufacturing, handling, and sterilization. Among other effects, trace materials may be inadvertently added at many steps of the manufacturing processes, and these can affect in vivo performance. Even raw material identification is subject to uncertainty and variability with respect to the supplier, to permissible ranges in specifications, and to actual content and residual materials that may be intentionally or unintentionally present. In this regard, the notion of two materials being “identical” is often a loose one. Changes in material manufacturing processes can affect biocompatibility test results. According to an anecdote told in a recent biocompatibility webinar, a supplier began requiring the use of gloves in handling the material, and then glove residue had an adverse effect on test results.
The physical form of a material also can play an important role in how the body responds to an implant. In particular, solid forms can produce different responses from porous forms or meshes even when both are made from a nominally similar material. For example, ingrowth, and the later maturation of ingrown tissue, may alter the overall geometry of a mesh but not of a solid, or it might stress a component in a way that produces a secondary adverse effect (e.g., fracture or buckling). The development of infection around an implant and the ability to treat such infections are also linked to physical structure, among other factors. Nanomaterials, or nanoized surfaces, are generally intended to expressly alter the tissue response to a material even when the material is otherwise familiar. In this case, it is the surface topography rather than the material itself that is being manipulated.
Recent concerns about breast implants illustrate the potential for physical form to play a significant role in endpoint biocompatibility. Current breast implants in the United States are available with two different surface finishes, either smooth or “textured” silicone. The objective of the textured surface is to limit movement and reduce the formation of overly tight scar tissue. It is noteworthy here that the function of the textured surface depends on its ability to alter tissue response. Yet this can lead to inconsistent thinking in which positive effects of surface changes are touted while negative effects are denied.
Unfortunately, textured surfaces on breast implants have also been linked to the development of Anaplastic Large Cell Lymphoma (ALCL), an adverse effect beyond any associated just with the long-term presence of silicone. FDA has noted that factors influencing ALCL include the methods used to create the textured surface and the role of biofilm in harboring bacteria. The latter may be influenced by interoperative interaction of the implant with the OR environment. There are two methods of texturizing identified by FDA: a stamping process and a “salt loss” process. There are currently four manufacturers of approved breast implants on the U.S. market. Three of these manufacturers have multiple products including smooth and textured and gel or saline filled. One manufacturer has only a smooth product. One textured implant has been recalled in Europe after renewal of its CE Mark was denied, and France has banned some products including ones not available in the United States. Two manufacturers in the United States have received warning letters from FDA criticizing their failure to fulfill their post-approval study requirements. More generally, adverse-event reporting such as MDR [Medical Device Reporting] is a weak process in terms of the number of cases captured and the completeness of the associated data. An effective implant registry can be somewhat better at collecting meaningful data, and there are currently two such registries in the United States that are voluntary and have different target populations. Overall the role of surface texture in ALCL remains inconclusive.
Implant biocompatibility is a complex property of a finished medical device and its interaction with the living host, including host variability. In this context, material and structural characterization of the tissue interface can play a critical role in determining biocompatibility. Oversimplifying material characterization (e.g., it’s silicone) can lead to unexpected adverse events such as ALCL in breast implants.