Nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives
Bioadhesives are a current unmet clinical need for mending of blood contacting soft tissues without inducing thrombosis. Recent development of carbene precursor bioadhesives with the advantages of on-demand curing, tuneable modulus, and wet adhesion have been synthesized by grafting diazirine onto p...
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sg-ntu-dr.10356-1371762023-07-14T15:57:57Z Nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives Nanda, Himansu Sekhar Shah, Ankur Harish Wicaksono, Gautama Pokholenko, Oleksandr Gao, Feng Djordjevic, Ivan Steele, Terry W. J. School of Materials Science & Engineering Engineering::Materials Bioadhesives Platelets Bioadhesives are a current unmet clinical need for mending of blood contacting soft tissues without inducing thrombosis. Recent development of carbene precursor bioadhesives with the advantages of on-demand curing, tuneable modulus, and wet adhesion have been synthesized by grafting diazirine onto poly (amidoamine) (PAMAM-G5) dendrimers. Herein, the structure activity relationships of platelet adhesion and activation is evaluated for the first time on the cured PAMAM-g-diazirine bioadhesives. Three strategies were employed to prevent healthy human donor platelets from adhering and activating on light-cured bioadhesive surfaces: (1) Attenuation of cationic surface charge, (2) antifouling composites by incorporating heparin and alginate in uncured formulation, and (3) heparin wash of cured bioadhesive surface. Topographical imaging of cured and ethanol dehydrated bioadhesive surfaces was used to quantify the adhered and activated platelets with scanning electron microscopy, whose resolution allowed identification of round senescent, short dendritic, and long dendritic platelets. Cured surfaces of PAMAM-g-diazirine (15%) had 10300 ± 500 adhered platelets mm-2 with 99.7% activation into short/long dendritic cells. Reduction of primary amines by higher degree of diazirine grafting or capping of free amines by acetylation reduces platelet adherence (2400 ± 200 vs 3000 ± 300, respectively). Physical incorporation of heparin and alginate in the formulations reduced the activated platelet; 1300 ± 300 and 300 ± 50, activated platelets mm-2, in comparison with additive free adhesive formulation. Similarly, heparin rinse of the surface of additive free bioadhesive reduced the activated platelet to platelets of heparin composites at 600 ± 100 platelets mm-2. PAMAM-g-diazirine (15%) bioadhesive retained the photocured mechanical properties and lap shear adhesion despite the addition of heparin and alginate additives. MOE (Min. of Education, S’pore) Accepted version 2020-03-04T08:38:47Z 2020-03-04T08:38:47Z 2018 Journal Article Nanda, H. S., Shah, A. H., Wicaksono, G., Pokholenko, O., Gao, F., Djordjevic, I., & Steele, T. W. J. (2018). Nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives. Biomacromolecules, 19(5), 1425-1434. doi:10.1021/acs.biomac.8b00074 1525-7797 https://hdl.handle.net/10356/137176 10.1021/acs.biomac.8b00074 29425441 2-s2.0-85044838440 5 19 1425 1434 en Biomacromolecules This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biomac.8b00074 application/pdf |
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Engineering::Materials Bioadhesives Platelets Nanda, Himansu Sekhar Shah, Ankur Harish Wicaksono, Gautama Pokholenko, Oleksandr Gao, Feng Djordjevic, Ivan Steele, Terry W. J. Nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives |
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Bioadhesives are a current unmet clinical need for mending of blood contacting soft tissues without inducing thrombosis. Recent development of carbene precursor bioadhesives with the advantages of on-demand curing, tuneable modulus, and wet adhesion have been synthesized by grafting diazirine onto poly (amidoamine) (PAMAM-G5) dendrimers. Herein, the structure activity relationships of platelet adhesion and activation is evaluated for the first time on the cured PAMAM-g-diazirine bioadhesives. Three strategies were employed to prevent healthy human donor platelets from adhering and activating on light-cured bioadhesive surfaces: (1) Attenuation of cationic surface charge, (2) antifouling composites by incorporating heparin and alginate in uncured formulation, and (3) heparin wash of cured bioadhesive surface. Topographical imaging of cured and ethanol dehydrated bioadhesive surfaces was used to quantify the adhered and activated platelets with scanning electron microscopy, whose resolution allowed identification of round senescent, short dendritic, and long dendritic platelets. Cured surfaces of PAMAM-g-diazirine (15%) had 10300 ± 500 adhered platelets mm-2 with 99.7% activation into short/long dendritic cells. Reduction of primary amines by higher degree of diazirine grafting or capping of free amines by acetylation reduces platelet adherence (2400 ± 200 vs 3000 ± 300, respectively). Physical incorporation of heparin and alginate in the formulations reduced the activated platelet; 1300 ± 300 and 300 ± 50, activated platelets mm-2, in comparison with additive free adhesive formulation. Similarly, heparin rinse of the surface of additive free bioadhesive reduced the activated platelet to platelets of heparin composites at 600 ± 100 platelets mm-2. PAMAM-g-diazirine (15%) bioadhesive retained the photocured mechanical properties and lap shear adhesion despite the addition of heparin and alginate additives. |
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School of Materials Science & Engineering |
author_facet |
School of Materials Science & Engineering Nanda, Himansu Sekhar Shah, Ankur Harish Wicaksono, Gautama Pokholenko, Oleksandr Gao, Feng Djordjevic, Ivan Steele, Terry W. J. |
format |
Article |
author |
Nanda, Himansu Sekhar Shah, Ankur Harish Wicaksono, Gautama Pokholenko, Oleksandr Gao, Feng Djordjevic, Ivan Steele, Terry W. J. |
author_sort |
Nanda, Himansu Sekhar |
title |
Nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives |
title_short |
Nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives |
title_full |
Nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives |
title_fullStr |
Nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives |
title_full_unstemmed |
Nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives |
title_sort |
nonthrombogenic hydrogel coatings with carbene-cross-linking bioadhesives |
publishDate |
2020 |
url |
https://hdl.handle.net/10356/137176 |
_version_ |
1773551293363650560 |