An inflatable cuff may be adapted to seal a vessel of a patient, such as a trachea when associated with a medical device, such as an endotracheal tube. In one embodiment, an inflatable cuff made from multiple layers is provided where one or more layers are chosen to improve sealing of the tube in the vessel. In exemplary embodiments, the individual layers may improve sealing by swelling in the presence of moisture, being wettable by the tissues of the trachea, or both. In one implementation, the inflatable cuff may be made of any combination of layers that perform either or both of these functions.