Sheep, pig, and human platelet-material interactions with model cardiovascular biomaterials

TLDR

Platelet-mediated thrombus formation is a key determinant of cardiovascular device hemocompatibility, yet translating animal performance to humans is not straightforward. The study compared sheep, pig, and human platelet adhesion, spreading, and thrombus-like structure formation on pyrolytic carbon, NIH polyethylene, silicone rubber, and Formvar in vitro. Porcine platelets behaved similarly to human platelets—extensive spreading on pyrolytic carbon and thrombus-like structures on Formvar—while sheep platelets were markedly less active, indicating pigs are a better predictor of human platelet‑biomaterial interactions.

Abstract

The relationship between cardiovascular device performance in animals and humans is not straightforward. As the principal formed element in a thrombus, platelets play a major role in determining the hemocompatibility of mechanical heart valves and other high-shear-rate cardiovascular devices. Since larger animals are required to test many such devices, sheep and porcine platelet responses were compared to humans. Adhesion, spreading, and the formation of thrombilike structures were examined in vitro on pyrolytic carbon mechanical heart valve leaflets, National Institutes of Health-reference polyethylene and silicone rubber, and Formvar. Principal findings were that platelet responses are strongly dependent upon the biomaterial and the species: Porcine and human platelets spread extensively on pyrolytic carbon, formed thrombuslike structures on Formvar, and were least active on silicone rubber. Human and porcine platelets responded differently to polyethylene: Human platelets spread extensively, while porcine platelets remained pseudopodial. In contrast, sheep platelets attached much less, never reached fully spread shapes, and were far less active overall. Since porcine responses were generally similar to humans, pigs may be a useful predictor of in vivo platelet-biomaterial interaction in humans. Conversely, as ovine platelets were much less active, this must be accounted for in the evaluation of cardiovascular devices tested in sheep.