Biomaterial and cellular implants:foreign surfaces where immunity and coagulation meet.

Exposure of blood to a foreign surface in the form of a diagnostic or therapeutic biomaterial device or implanted cells or tissues, elicits an immediate, evolutionarily conserved thrombo-inflammatory response by the host. Primarily designed to protect against invading organisms following an injury, this innate response features instantaneous activation of several blood-borne, highly interactive and well-orchestrated cascades and cellular events that limit bleeding, destroy and eliminate the foreign substance/cells, and promote healing and a return to homeostasis via delicately balanced regenerative processes. In the setting of blood-contacting synthetic or natural biomaterials and implantation of foreign cells/tissues, innate responses are robust, albeit highly context-specific. Unfortunately, they tend to be less than adequately regulated by the host's natural anti-coagulant/anti-inflammatory pathways, thereby jeopardizing the functional integrity of the device, as well as the health of the host. Strategies to achieve biocompatibility with a sustained return to homeostasis, particularly while the device remains in situ and functional, continue to elude scientists and clinicians. In this review, some of the complex mechanisms by which biomaterials and cellular transplants provide a "hub" for activation and amplification of coagulation and immunity - thrombo-inflammation - will be discussed, with a view toward the development of innovative means of overcoming the innate challenges.