Surface-targeted complement modulation at biomedical interfaces

The complement system is essential for distinguishing self-tissue from foreign threats; however, complement activation on biomedical surfaces such as implants, transplants, or drug-delivery systems may lead to severe thromboinflammatory complications. Unlike systemic complement inhibitors, surface-targeted strategies remain scarce, despite their potential advantages regarding safety and efficacy. Recent years have seen the emergence of diverse surface-targeting approaches that impair different mechanisms underlying complement-mediated complications. These strategies, ranging from surface coatings to inhibitors targeting complement-tagged surfaces, are progressing from conceptual development to clinical application. In this review, we provide a comprehensive overview of complement-activation mechanisms on biomedical surfaces, highlight ongoing clinical investigations, and discuss a broad spectrum of emerging approaches to prevent adverse complement activation on biomedical interfaces.