Chitosan-Platelet Interactions

Since chitosan was identified as a hemostatic agent in the 1980s, "chitosan and platelets" has developed into a topic of intense interest. This chapter gives an overview of platelet biogenesis, composition, activation, and mechanisms implicated in chitosan-platelet interactions. Chitosan is a unique acid-soluble cationic glucosamine polysaccharide with tunable molecular weight, glucosamine/Nacetyl glucosamine content, and acetylation pattern. Platelets are small anuclear cells with anionic surfaces that are released to the blood stream by megakaryocytes that reside in bone marrow and the lung. Platelets are stocked with granules that contain a plethora of bioactive wound-healing and procoagulant factors. Upon activation by agonists, or adhesion to von Willebrand factor "strings" under shear stress, platelets aid in fibrin clot formation to seal off a wound and initiate wound repair. Purified platelets rapidly adhere to a variety of solid chitosan and chitin substrates but show inconsistent levels of activation in the absence of calcium. Chitosans with a positive charge state bind to platelets and potentiate alpha granule release in whole blood or recalcified platelet-rich plasma (PRP). Platelet activation kinetics were accelerated by higher chitosan deacetylation levels and molecular weight (95% vs. 80% deacetylated, 177 kDa vs. 102 kDa), but mis-timed platelet degranulation prior to thrombin activation led to weaker clot tensile strength. Neutral-soluble chitosans (oligomers, 50% reacetylated chitosans) do not activate platelets and hydrophobic butyryl-chitosan coatings inhibit platelet adhesion. Collective data suggest two mechanisms underlying chitosan-platelet interactions: (1) non-specific electrostatic binding of anionic platelets to positively charged chitosan surfaces, and (2) platelet binding to blood plasma factors adsorbed on chitosan or chitin surfaces. Future directions include deepening our understanding of the molecular basis for thrombocyte-chitosan interactions, and the performance of platelet-activating chitosan formulations in clinically relevant contexts where platelet physiology is altered by medications, trauma, or disease.