Poster W4 - Anatomical location and alloy/surface treatment composition-specific immune responses to metallic implants

Introduction: Metals comprise a major portion of the medical implant field. Their applications range from joint replacements and structural supports to conductors and sensors. Composition of these materials varies widely with use as innovation has provided newer more versatile alloys capable of functions beyond just structural. However, it has been noted that the immune system can react in a unique manner depending on the material used and where it is implanted. While the traditional site of biocompatibility testing has been subcutaneous, it has been suggested that tissue-specific immune profiles can play a major role in how an implant is perceived by the host immune system. The material may be well-tolerated in the subcutaneous space yet initiate a different immune response in the site of therapeutic relevance. Furthermore, as the immune reaction mounts, device functionality can be compromised. Recruited immune populations may lead to foreign body response (FBR), and in the case of metallic implants, corrosion. As corrosion ensues, these implants can leach metal ions and release larger debris that may remain locally and perpetuate chronic inflammation. There is also speculation that these same degradation species can travel systemically depending on access to circulation, potentially affecting other tissues distant from the implant site. With this in mind, we are determining how anatomical implant location as well as metallic composition impacts the host immunity, both locally and systemically.

Materials and

Methods: We are studying multiple miniaturized metallic implants relevant to the clinic. With the help of veterinary staff, we have optimized surgical approaches for several surgeries to be applied in rodent animal models (mouse and rat). These surgeries span several anatomical locations covering various factors of interest: microenvironment liquid turnover, extracellular matrix architecture, and unique immune composition. At various timepoints, animals are euthanized, and tissue samples taken for gene expression (qPCR, NanoString) and cellular response (flow cytometry, IF, histology, and 3D lightsheet microscopy) analyses. In addition, material surfaces are tested for chemical modification/corrosion (SEM-EDS). Leached ion species can also be detected in situ through spatial analyses including MALDI-TOF-MS and ICP-MS.

Results, Conclusions, and Discussions: Through our analyses of various local and systemic tissues, there are observable differences in the immune response to individual material systems. This is conserved in the case of unique compositions of the bulk material used in the same application, as well as with and without an applied surface coating/treatment (e.g., passivation or oxide layer). Most significantly, the observed immune response notably changes when the materials are implanted in different anatomical locations. Further, the immune reaction returns to baseline over the course of the study in one implant location, whereas it is maintained chronically at another. We have also obtained incredible 3D spatial, single-cell resolution immune localization data around implants utilizing lightsheet microscopy, and expect such evidence will lead to improved understanding of both infiltration events as well as local immune dynamics.

Data collected imply both material choice, including bulk composition and surface treatments, as well as implant location may play pivotal roles in the success and longevity of metallic medical devices. Moving forward, it is our hope this information will help device manufacturers develop improved future technologies, inform patients and clinicians alike to make more informed choices for improved health outcomes, and lead to improved regulatory oversight for how such material device systems are tested and approved for specific use(s).

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