Novel Platelet Substitutes: Disk-Shaped Biodegradable Nanosheets and their Enhanced Effects on Platelet Aggregation

We have studied biocompatible spherical carriers carrying a dodecapeptide, HHLGGAKQAGDV (H12), on their surface as platelet substitutes. This peptide is a fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411) and specifically recognizes the active form of glycoprotein IIb/IIIa on activated platelets. Our purpose is to assess the possibility of making a novel platelet substitute consisting of disk-shaped nanosheets having a large contact area for the targeting site, rather than conventional small contact area spherical carriers. ne H12 peptide was conjugated to the surface of the free-standing nanosheets made of biodegradable poly(D,L-lactide-co-glycolide) (PLGA). These H12-PLGA nanosheets were fabricated onto 3 mu m disk-shaped patterned hydrophobic octadecyl regions on a SiO2 substrate. By way of comparison, spherical H12-PLGA microparticles with the same surface area and conjugation number of H12 were also prepared. The resulting H12-PLGA nanosheets specifically interacted with the activated platelets adhered on the collagen surface at twice the rate of the H12-PLGA microparticles under flow conditions, and showed platelet thrombus formation in a two-dimensional spreading manner. Thus, H12-PLGA nanosheets might be a suitable candidate novel platelet alternative substitute for infused human platelet concentrates for the treatment of bleeding in patients with severe thrombocytopenia.