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 γ-chain carboxy-terminal sequence (γ400-411) 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. The 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 μm disk-shaped patterned hydrophobic octadecyl regions on a SiO(2) 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.
Okamura
Yosuke
Y
Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, TWIns, Tokyo, Japan.
Fukui
Yoshihito
Y
Kabata
Koki
K
Suzuki
Hidenori
H
Handa
Makoto
M
Ikeda
Yasuo
Y
Takeoka
Shinji
S
D058045:Artificial Cells / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D001792:Blood Platelets / Q000378:metabolism*; D005340:Fibrinogen / Q000737:chemistry*; D006470:Hemorrhage / Q000628:therapy; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry* / Q000627:therapeutic use; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012822:Silicon Dioxide / Q000737:chemistry*; D013921:Thrombocytopenia / Q000628:therapy; D013927:Thrombosis
D009842:Oligopeptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012822:Silicon Dioxide; D005340:Fibrinogen