Selective Immunosuppression Targeting the NLRP3 Inflammasome Mitigates the Foreign Body Response to Implanted Biomaterials While Preserving Angiogenesis

• Published in: Advanced healthcare materials 2023-12, Vol.12 (32), p.e2301571-n/a
• Main Authors: Chan, Alex H.P., Moore, Matthew J., Grant, Angus J., Lam, Yuen Ting Monica, Darnell, Matthew V., Michael, Praveesuda L., Wise, Steven G., Tan, Richard P.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Biomaterials; Biomedical materials; Dexamethasone; Electronic implants; Fibrosis; Foreign bodies; foreign body responses; Immune response; Immune system; Immunosuppression; Immunosuppressive agents; implantable devices; Inflammasomes; Inflammation; Medical devices; Medical electronics; Medical equipment; NLRP3 inflammasome; Polycaprolactone; Regeneration (physiology); Surgical implants; Tissue engineering
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202301571

Medical devices are a mainstay of the healthcare industry, providing clinicians with innovative tools to diagnose, monitor, and treat a range of medical conditions. For implantable devices, it is widely regarded that chronic inflammation during the foreign body response (FBR) is detrimental to device performance, but also required for tissue regeneration and host integration. Current strategies to mitigate the FBR rely on broad acting anti‐inflammatory drugs, most commonly, dexamethasone (DEX), which can inhibit angiogenesis and compromise long‐term device function. This study challenges prevailing assumptions by suggesting that FBR inflammation is multifaceted, and selectively targeting its individual pathways can stop implant fibrosis while preserving beneficial repair pathways linked to improved device performance. MCC950, an anti‐inflammatory drug that selectively inhibits the NLRP3 inflammasome, targets pathological inflammation without compromising global immune function. The effects of MCC950 and DEX on the FBR are compared using implanted polycaprolactone (PCL) scaffolds. The results demonstrate that both DEX and MCC950 halt immune cell recruitment and cytokine release, leading to reduced FBR. However, MCC950 achieves this while supporting capillary growth and enhancing tissue angiogenesis. These findings support selective immunosuppression approaches as a potential future direction for treating the FBR and enhancing the longevity and safety of implantable devices. Inhibition of the NLRP3 inflammasome using MCC950 results in similar reductions in fibrotic response compared to broad spectrum anti‐inflammatory agents such as dexamethasone. Selective targeting of NLRP3 preserves the critical elements of inflammation resolution and promotes angiogenesis and host tissue integration which is required for the long‐term functions of implanted medical device.