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Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering

Fibrin has been used clinically for wound coverings, surgical glues, and cell delivery because of its affordability, cytocompatibility, and ability to modulate angiogenesis and inflammation. However, its rapid degradation rate has limited its usefulness as a scaffold for 3D cell culture and tissue e...

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Autores principales: Jarrell, Dillon K., Vanderslice, Ethan J., Lennon, Mallory L., Lyons, Anne C., VeDepo, Mitchell C., Jacot, Jeffrey G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133424/
https://www.ncbi.nlm.nih.gov/pubmed/34010323
http://dx.doi.org/10.1371/journal.pone.0239242
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author Jarrell, Dillon K.
Vanderslice, Ethan J.
Lennon, Mallory L.
Lyons, Anne C.
VeDepo, Mitchell C.
Jacot, Jeffrey G.
author_facet Jarrell, Dillon K.
Vanderslice, Ethan J.
Lennon, Mallory L.
Lyons, Anne C.
VeDepo, Mitchell C.
Jacot, Jeffrey G.
author_sort Jarrell, Dillon K.
collection PubMed
description Fibrin has been used clinically for wound coverings, surgical glues, and cell delivery because of its affordability, cytocompatibility, and ability to modulate angiogenesis and inflammation. However, its rapid degradation rate has limited its usefulness as a scaffold for 3D cell culture and tissue engineering. Previous studies have sought to slow the degradation rate of fibrin with the addition of proteolysis inhibitors or synthetic crosslinkers that require multiple functionalization or polymerization steps. These strategies are difficult to implement in vivo and introduce increased complexity, both of which hinder the use of fibrin in research and medicine. Previously, we demonstrated that additional crosslinking of fibrin gels using bifunctionalized poly(ethylene glycol)-n-hydroxysuccinimide (PEG-NHS) slows the degradation rate of fibrin. In this study, we aimed to further improve the longevity of these PEG-fibrin gels such that they could be used for tissue engineering in vitro or in situ without the need for proteolysis inhibitors. It is well documented that increasing the salinity of fibrin precursor solutions affects the resulting gel morphology. Here, we investigated whether this altered morphology influences the fibrin degradation rate. Increasing the final sodium chloride (NaCl) concentration from 145 mM (physiologic level) to 250 mM resulted in fine, transparent high-salt (HS) fibrin gels that degrade 2–3 times slower than coarse, opaque physiologic-salt (PS) fibrin gels both in vitro (when treated with proteases and when seeded with amniotic fluid stem cells) and in vivo (when injected subcutaneously into mice). Increased salt concentrations did not affect the viability of encapsulated cells, the ability of encapsulated endothelial cells to form rudimentary capillary networks, or the ability of the gels to maintain induced pluripotent stem cells. Finally, when implanted subcutaneously, PS gels degraded completely within one week while HS gels remained stable and maintained viability of seeded dermal fibroblasts. To our knowledge, this is the simplest method reported for the fabrication of fibrin gels with tunable degradation properties and will be useful for implementing fibrin gels in a wide range of research and clinical applications.
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spelling pubmed-81334242021-05-27 Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering Jarrell, Dillon K. Vanderslice, Ethan J. Lennon, Mallory L. Lyons, Anne C. VeDepo, Mitchell C. Jacot, Jeffrey G. PLoS One Research Article Fibrin has been used clinically for wound coverings, surgical glues, and cell delivery because of its affordability, cytocompatibility, and ability to modulate angiogenesis and inflammation. However, its rapid degradation rate has limited its usefulness as a scaffold for 3D cell culture and tissue engineering. Previous studies have sought to slow the degradation rate of fibrin with the addition of proteolysis inhibitors or synthetic crosslinkers that require multiple functionalization or polymerization steps. These strategies are difficult to implement in vivo and introduce increased complexity, both of which hinder the use of fibrin in research and medicine. Previously, we demonstrated that additional crosslinking of fibrin gels using bifunctionalized poly(ethylene glycol)-n-hydroxysuccinimide (PEG-NHS) slows the degradation rate of fibrin. In this study, we aimed to further improve the longevity of these PEG-fibrin gels such that they could be used for tissue engineering in vitro or in situ without the need for proteolysis inhibitors. It is well documented that increasing the salinity of fibrin precursor solutions affects the resulting gel morphology. Here, we investigated whether this altered morphology influences the fibrin degradation rate. Increasing the final sodium chloride (NaCl) concentration from 145 mM (physiologic level) to 250 mM resulted in fine, transparent high-salt (HS) fibrin gels that degrade 2–3 times slower than coarse, opaque physiologic-salt (PS) fibrin gels both in vitro (when treated with proteases and when seeded with amniotic fluid stem cells) and in vivo (when injected subcutaneously into mice). Increased salt concentrations did not affect the viability of encapsulated cells, the ability of encapsulated endothelial cells to form rudimentary capillary networks, or the ability of the gels to maintain induced pluripotent stem cells. Finally, when implanted subcutaneously, PS gels degraded completely within one week while HS gels remained stable and maintained viability of seeded dermal fibroblasts. To our knowledge, this is the simplest method reported for the fabrication of fibrin gels with tunable degradation properties and will be useful for implementing fibrin gels in a wide range of research and clinical applications. Public Library of Science 2021-05-19 /pmc/articles/PMC8133424/ /pubmed/34010323 http://dx.doi.org/10.1371/journal.pone.0239242 Text en © 2021 Jarrell et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jarrell, Dillon K.
Vanderslice, Ethan J.
Lennon, Mallory L.
Lyons, Anne C.
VeDepo, Mitchell C.
Jacot, Jeffrey G.
Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering
title Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering
title_full Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering
title_fullStr Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering
title_full_unstemmed Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering
title_short Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering
title_sort increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133424/
https://www.ncbi.nlm.nih.gov/pubmed/34010323
http://dx.doi.org/10.1371/journal.pone.0239242
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