Improved Medical Implants Could Influence Immune System to Help Instead of Harming the Body

Medical implants like pacemakers, breast implants, or knee replacements can sometimes create unfavorable immune reactions that harm both the implant and the nearby tissue. The standard clinical approach to handle this has been to use immunosuppressive drugs, which don't always work effectively and carry significant risks. When these immune-related complications arise, patients often require additional surgeries to replace or remove the compromised implants. Though scientists don't yet fully understand why these immune responses occur, new research is shedding light on some crucial factors.

Natural implants, such as tissue grafts, have been found to guide the immune system in a more positive direction by encouraging healing processes. While natural materials can't be used for all medical applications, the lessons they provide can be valuable for other types of implants. Researchers at the National Institute of Biomedical Imaging and Bioengineering (NIBIB, Bethesda, MD, USA) studied how the immune system reacts differently to two materials implanted in mice. Their findings help lay the groundwork for designing medical devices that could work in harmony with the immune system, rather than against it.

To explore the differences in immune responses to various materials, scientists removed muscle from the legs of mice and filled the gaps with two different materials. One was decellularized small intestinal submucosa, which is pig tissue stripped of its cells, leaving mostly collagen. This material has been shown to encourage healing processes. The other was polyethylene, a plastic often used in orthopedic implants, known to cause long-term inflammation and scarring. A third group of mice with muscle removed was left untreated as a control group.

By employing flow cytometry, the researchers identified and counted various cell types in the tissue taken from the mice. As anticipated, samples with the submucosa showed a greater tendency towards anti-inflammatory reactions and healing compared to the polyethylene samples. Notably, one specific cell type, called cDC1s and belonging to the dendritic cell class, was much more prevalent in the submucosa samples. Dendritic cells help the immune system distinguish between harmful and harmless entities. When these dendritic cells were genetically blocked in mice, both inflammation and scarring increased, irrespective of the implanted material.

Additional experiments revealed that a type of immune cell called natural killer cells were signaling for the recruitment of this specific dendritic cell subtype, a process commonly seen in tumor-related immune responses. The researchers believe that molecular signals likely present in pig submucosa but not in polyethylene could be the reason for the different immune reactions observed. Moving forward, the research team aims to pinpoint the specific proteins and molecules that trigger these healing responses. Their goal is to incorporate these molecules into existing or new medical devices to make them more compatible with the body's immune system, thus increasing their safety and longevity.

“Implants frequently cause pain and, in many cases, need to be removed within a few years. We’re looking to eventually eliminate that grief by extending the lifespan of implanted medical devices to the lifespan of patients,” said Kaitlyn Sadtler, Ph.D., Earl Stadtman Tenure-Track Investigator and chief of the Section on Immunoengineering at NIBIB. “If we could tease out what aspect of these different materials causes certain immune responses, we would have more control in designing materials and devices that encourage the responses we want.”

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