Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer
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 ble...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Lamm, Robert J. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2017transfer abstract |
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| Schlagwörter: |
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| Umfang: |
9 |
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| Übergeordnetes Werk: |
Enthalten in: Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field - 2012, biomaterials reviews online, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:132 ; year:2017 ; pages:96-104 ; extent:9 |
| Links: |
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| DOI / URN: |
10.1016/j.biomaterials.2017.04.002 |
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| 520 | |a 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. | ||
| 520 | |a 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. | ||
| 650 | 7 | |a Synthetic injectable hemostat |2 Elsevier | |
| 650 | 7 | |a Fibrin-binding polymer |2 Elsevier | |
| 650 | 7 | |a Ligand density |2 Elsevier | |
| 650 | 7 | |a Peptide-polymer conjugate |2 Elsevier | |
| 700 | 1 | |a Lim, Esther B. |4 oth | |
| 700 | 1 | |a Weigandt, Katie M. |4 oth | |
| 700 | 1 | |a Pozzo, Lilo D. |4 oth | |
| 700 | 1 | |a White, Nathan J. |4 oth | |
| 700 | 1 | |a Pun, Suzie H. |4 oth | |
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10.1016/j.biomaterials.2017.04.002 doi GBVA2017003000015.pica (DE-627)ELV030264308 (ELSEVIER)S0142-9612(17)30210-7 DE-627 ger DE-627 rakwb eng 570 570 DNB 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Lamm, Robert J. verfasserin aut Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer 2017transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. Synthetic injectable hemostat Elsevier Fibrin-binding polymer Elsevier Ligand density Elsevier Peptide-polymer conjugate Elsevier Lim, Esther B. oth Weigandt, Katie M. oth Pozzo, Lilo D. oth White, Nathan J. oth Pun, Suzie H. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:132 year:2017 pages:96-104 extent:9 https://doi.org/10.1016/j.biomaterials.2017.04.002 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 132 2017 96-104 9 045F 570 |
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10.1016/j.biomaterials.2017.04.002 doi GBVA2017003000015.pica (DE-627)ELV030264308 (ELSEVIER)S0142-9612(17)30210-7 DE-627 ger DE-627 rakwb eng 570 570 DNB 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Lamm, Robert J. verfasserin aut Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer 2017transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. Synthetic injectable hemostat Elsevier Fibrin-binding polymer Elsevier Ligand density Elsevier Peptide-polymer conjugate Elsevier Lim, Esther B. oth Weigandt, Katie M. oth Pozzo, Lilo D. oth White, Nathan J. oth Pun, Suzie H. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:132 year:2017 pages:96-104 extent:9 https://doi.org/10.1016/j.biomaterials.2017.04.002 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 132 2017 96-104 9 045F 570 |
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10.1016/j.biomaterials.2017.04.002 doi GBVA2017003000015.pica (DE-627)ELV030264308 (ELSEVIER)S0142-9612(17)30210-7 DE-627 ger DE-627 rakwb eng 570 570 DNB 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Lamm, Robert J. verfasserin aut Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer 2017transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. Synthetic injectable hemostat Elsevier Fibrin-binding polymer Elsevier Ligand density Elsevier Peptide-polymer conjugate Elsevier Lim, Esther B. oth Weigandt, Katie M. oth Pozzo, Lilo D. oth White, Nathan J. oth Pun, Suzie H. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:132 year:2017 pages:96-104 extent:9 https://doi.org/10.1016/j.biomaterials.2017.04.002 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 132 2017 96-104 9 045F 570 |
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10.1016/j.biomaterials.2017.04.002 doi GBVA2017003000015.pica (DE-627)ELV030264308 (ELSEVIER)S0142-9612(17)30210-7 DE-627 ger DE-627 rakwb eng 570 570 DNB 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Lamm, Robert J. verfasserin aut Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer 2017transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. Synthetic injectable hemostat Elsevier Fibrin-binding polymer Elsevier Ligand density Elsevier Peptide-polymer conjugate Elsevier Lim, Esther B. oth Weigandt, Katie M. oth Pozzo, Lilo D. oth White, Nathan J. oth Pun, Suzie H. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:132 year:2017 pages:96-104 extent:9 https://doi.org/10.1016/j.biomaterials.2017.04.002 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 132 2017 96-104 9 045F 570 |
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10.1016/j.biomaterials.2017.04.002 doi GBVA2017003000015.pica (DE-627)ELV030264308 (ELSEVIER)S0142-9612(17)30210-7 DE-627 ger DE-627 rakwb eng 570 570 DNB 570 VZ BIODIV DE-30 fid 35.70 bkl 42.12 bkl 42.15 bkl Lamm, Robert J. verfasserin aut Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer 2017transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier 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. 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. Synthetic injectable hemostat Elsevier Fibrin-binding polymer Elsevier Ligand density Elsevier Peptide-polymer conjugate Elsevier Lim, Esther B. oth Weigandt, Katie M. oth Pozzo, Lilo D. oth White, Nathan J. oth Pun, Suzie H. oth Enthalten in Elsevier Science Lymphotoxin in the Pathogenesis of Autoimmune Pancreatitis: A New Player in the Field 2012 biomaterials reviews online Amsterdam [u.a.] (DE-627)ELV011266368 volume:132 year:2017 pages:96-104 extent:9 https://doi.org/10.1016/j.biomaterials.2017.04.002 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA 35.70 Biochemie: Allgemeines VZ 42.12 Biophysik VZ 42.15 Zellbiologie VZ AR 132 2017 96-104 9 045F 570 |
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peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer |
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Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer |
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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. |
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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. |
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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. |
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