Cross‐Linked Zwitterionic Surface Modifications for Biocompatible Blood‐Contacting Medical Devices

ABSTRACT Blood‐contacting medical devices, such as vascular catheters, heart valves, membrane oxygenators, or dialysis membranes, enable the treatment and long‐term care of countless people suffering from cardiovascular, respiratory, and renal diseases. These devices are largely constructed from polymeric materials, and despite advancements in material biocompatibility, remain susceptible to adverse biological processes such as thrombosis, inflammation, and calcification, introducing risks to patient safety and constraining long‐term device performance. This article builds on previous research that introduced a plasma‐mediated zwitterion surface modification by chemically cross‐linking the zwitterionic graft to improve graft stability, examining biological responses to these modifications, and adapting the protocol to device geometries. By chemically cross‐linking the zwitterionic graft with a specific zwitterion:crosslinker ratio, the stability of the graft can be extended without compromising its functional efficacy. These cross‐linked zwitterion grafts drive reductions in 1) thrombus formation in static and dynamic in vitro models, 2) inflammatory responses via a mixture of in vitro inflammatory cytokine expression and in vivo M1 macrophage counts, and 3) mineral deposition via in vitro calcification assays. Finally, the grafting process can be applied to vascular and valvular geometries, highlighting its translational potential to a range of medical devices.