Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer

التفاصيل البيبلوغرافية
العنوان: Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer
المؤلفون: Esther B. Lim, Suzie H. Pun, Kathleen M. Weigandt, Nathan J. White, Robert J. Lamm, Lilo D. Pozzo
المصدر: Biomaterials. 132:96-104
بيانات النشر: Elsevier BV, 2017.
سنة النشر: 2017
مصطلحات موضوعية: Materials science, Kinetics, Biophysics, Hemorrhage, Bioengineering, Peptide, 02 engineering and technology, (Hydroxyethyl)methacrylate, 010402 general chemistry, 01 natural sciences, Article, Fibrin, Rats, Sprague-Dawley, Biomaterials, chemistry.chemical_compound, Animals, Humans, Blood Coagulation, chemistry.chemical_classification, Chitosan, Hemostasis, biology, Albumin, Thrombosis, Polymer, 021001 nanoscience & nanotechnology, Rats, Thrombelastography, 0104 chemical sciences, Thromboelastometry, Cross-Linking Reagents, chemistry, Biochemistry, Mechanics of Materials, Ceramics and Composites, biology.protein, Wounds and Injuries, Blood Coagulation Tests, Peptides, 0210 nano-technology, Conjugate
الوصف: Therapeutic polymers have the potential to improve the standard of care for hemorrhage, or uncontrolled bleeding, as synthetic hemostats. PolySTAT, a fibrin-crosslinking peptide-polymer conjugate, has the capacity to rescue fibrin clot formation and improve survival in a model of acute traumatic bleeding. PolySTAT consists of a synthetic polymer backbone to which targeting fibrin-binding peptides are linked. For translation of PolySTAT, the optimal valency of peptides must be determined. Grafting of fibrin-binding peptides to the poly(hydroxyethyl methacrylate)-based backbone was controlled to produce peptide valencies ranging from 0 to 10 peptides per polymer. PolySTATs with valencies of ≈4 or greater resulted in increased clot firmness, kinetics, and decreased breakdown as measured by thromboelastometry. A valency of ≈4 increased clot firmness 57% and decreased clot breakdown 69% compared to phosphate-buffered saline. This trend was characterized by neutron scattering, which probed the structure of clots formed in the presence of PolySTAT. Finally, PolySTAT with valencies of 4 (100% survival; p = 0.013) and 8 (80% survival; p = 0.063) improved survival compared to an albumin control in a femoral artery injury model (20% survival). This work demonstrates tunability of hemostatic polymers and the ability of in vitro assays to predict in vivo efficacy.
تدمد: 0142-9612
DOI: 10.1016/j.biomaterials.2017.04.002
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9d6d337a5611b08d0cbaae885bdf47dd
https://doi.org/10.1016/j.biomaterials.2017.04.002
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....9d6d337a5611b08d0cbaae885bdf47dd
قاعدة البيانات: OpenAIRE
الوصف
تدمد:01429612
DOI:10.1016/j.biomaterials.2017.04.002