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.
Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, TWIns, Tokyo, Japan.
Yosuke
Y
Okamura
Yoshihito
Y
Fukui
Koki
K
Kabata
Hidenori
H
Suzuki
Makoto
M
Handa
Yasuo
Y
Ikeda
Shinji
S
Takeoka
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