A gellan-based fluid gel carrier to enhance topical spray delivery

[Display omitted] Autologous cell transplantation was introduced to clinical practice nearly four decades ago to enhance burn wound re-epithelialisation. Autologous cultured or uncultured cells are often delivered to the surface in saline-like suspensions. This delivery method is limited because dro...

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Veröffentlicht in:Acta biomaterialia 2019-04, Vol.89, p.166-179
Hauptverfasser: ter Horst, B., Moakes, R.J.A., Chouhan, G., Williams, R.L., Moiemen, N.S., Grover, L.M.
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container_start_page 166
container_title Acta biomaterialia
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creator ter Horst, B.
Moakes, R.J.A.
Chouhan, G.
Williams, R.L.
Moiemen, N.S.
Grover, L.M.
description [Display omitted] Autologous cell transplantation was introduced to clinical practice nearly four decades ago to enhance burn wound re-epithelialisation. Autologous cultured or uncultured cells are often delivered to the surface in saline-like suspensions. This delivery method is limited because droplets of the sprayed suspension form upon deposition and run across the wound bed, leading to uneven coverage and cell loss. One way to circumvent this problem would be to use a gel-based material to enhance surface retention. Fibrin systems have been explored as co-delivery system with keratinocytes or as adjunct to ‘seal’ the cells following spray delivery, but the high costs and need for autologous blood has impeded its widespread use. Aside from fibrin gel, which can exhibit variable properties, it has not been possible to develop a gel-based carrier that solidifies on the skin surface. This is because it is challenging to develop a material that is sprayable but gels on contact with the skin surface. The manuscript reports the use of an engineered carrier device to deliver cells via spraying, to enhance retention upon a wound. The device involves shear-structuring of a gelling biopolymer, gellan, during the gelation process; forming a yield-stress fluid with shear-sensitive behaviours, known as a fluid gel. In this study, a formulation of gellan gum fluid gels are reported, formed with from 0.75 or 0.9% (w/v) polymer and varying the salt concentrations. The rheological properties and the propensity of the material to wet a surface were determined for polymer modified and non-polymer modified cell suspensions. The gellan fluid gels had a significantly higher viscosity and contact angle when compared to the non-polymer carrier. Viability of cells was not impeded by encapsulation in the gellan fluid gel or spraying. The shear thinning property of the material enabled it to be applied using an airbrush and spray angle, distance and air pressure were optimised for coverage and viability. Spray delivery of skin cells has successfully translated to clinical practice. However, it has not yet been widely accepted due to limited retention and disputable cell viability in the wound. Here, we report a method for delivering cells onto wound surfaces using a gellan-based shear-thinning gel system. The viscoelastic properties allow the material to liquefy upon spraying and restructure rapidly on the surface. Our results demonstrate reduced run-off from the surface compare
doi_str_mv 10.1016/j.actbio.2019.03.036
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Autologous cultured or uncultured cells are often delivered to the surface in saline-like suspensions. This delivery method is limited because droplets of the sprayed suspension form upon deposition and run across the wound bed, leading to uneven coverage and cell loss. One way to circumvent this problem would be to use a gel-based material to enhance surface retention. Fibrin systems have been explored as co-delivery system with keratinocytes or as adjunct to ‘seal’ the cells following spray delivery, but the high costs and need for autologous blood has impeded its widespread use. Aside from fibrin gel, which can exhibit variable properties, it has not been possible to develop a gel-based carrier that solidifies on the skin surface. This is because it is challenging to develop a material that is sprayable but gels on contact with the skin surface. The manuscript reports the use of an engineered carrier device to deliver cells via spraying, to enhance retention upon a wound. The device involves shear-structuring of a gelling biopolymer, gellan, during the gelation process; forming a yield-stress fluid with shear-sensitive behaviours, known as a fluid gel. In this study, a formulation of gellan gum fluid gels are reported, formed with from 0.75 or 0.9% (w/v) polymer and varying the salt concentrations. The rheological properties and the propensity of the material to wet a surface were determined for polymer modified and non-polymer modified cell suspensions. The gellan fluid gels had a significantly higher viscosity and contact angle when compared to the non-polymer carrier. Viability of cells was not impeded by encapsulation in the gellan fluid gel or spraying. The shear thinning property of the material enabled it to be applied using an airbrush and spray angle, distance and air pressure were optimised for coverage and viability. Spray delivery of skin cells has successfully translated to clinical practice. However, it has not yet been widely accepted due to limited retention and disputable cell viability in the wound. Here, we report a method for delivering cells onto wound surfaces using a gellan-based shear-thinning gel system. The viscoelastic properties allow the material to liquefy upon spraying and restructure rapidly on the surface. Our results demonstrate reduced run-off from the surface compared to currently used low-viscosity cell carriers. Moreover, encapsulated cells remain viable throughout the process. Although this paper studies the encapsulation of one cell type, a similar approach could potentially be adopted for other cell types. Our data supports further studies to confirm these results in in vivo models.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2019.03.036</identifier><identifier>PMID: 30904549</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Administration, Topical ; Autografts ; Biopolymers ; Cell suspensions ; Cell transplantation ; Cell viability ; Clinical medicine ; Contact angle ; Drug Carriers - chemistry ; Drug Carriers - pharmacology ; Encapsulation ; Fibrin ; Fluid gel ; Gelation ; Gellan gum ; Gels ; Gels - chemistry ; Gels - pharmacology ; Humans ; In vivo methods and tests ; Keratinocytes ; Keratinocytes - metabolism ; Keratinocytes - pathology ; Keratinocytes - transplantation ; Polymers ; Polysaccharides, Bacterial - chemistry ; Polysaccharides, Bacterial - pharmacology ; Properties (attributes) ; Retention ; Rheological properties ; Runoff ; Shear ; Shear thinning (liquids) ; Skin ; Spray therapies ; Spraying ; Thinning ; Transplantation ; Viscoelasticity ; Viscosity ; Wounds ; Yield-stress fluid</subject><ispartof>Acta biomaterialia, 2019-04, Vol.89, p.166-179</ispartof><rights>2019</rights><rights>Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Apr 15, 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-8d6b8f6cfa106ad29e541f93289f896ec0c289ec799d08fcb40e81daa90fe21f3</citedby><cites>FETCH-LOGICAL-c427t-8d6b8f6cfa106ad29e541f93289f896ec0c289ec799d08fcb40e81daa90fe21f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1742706119302119$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30904549$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ter Horst, B.</creatorcontrib><creatorcontrib>Moakes, R.J.A.</creatorcontrib><creatorcontrib>Chouhan, G.</creatorcontrib><creatorcontrib>Williams, R.L.</creatorcontrib><creatorcontrib>Moiemen, N.S.</creatorcontrib><creatorcontrib>Grover, L.M.</creatorcontrib><title>A gellan-based fluid gel carrier to enhance topical spray delivery</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted] Autologous cell transplantation was introduced to clinical practice nearly four decades ago to enhance burn wound re-epithelialisation. Autologous cultured or uncultured cells are often delivered to the surface in saline-like suspensions. This delivery method is limited because droplets of the sprayed suspension form upon deposition and run across the wound bed, leading to uneven coverage and cell loss. One way to circumvent this problem would be to use a gel-based material to enhance surface retention. Fibrin systems have been explored as co-delivery system with keratinocytes or as adjunct to ‘seal’ the cells following spray delivery, but the high costs and need for autologous blood has impeded its widespread use. Aside from fibrin gel, which can exhibit variable properties, it has not been possible to develop a gel-based carrier that solidifies on the skin surface. This is because it is challenging to develop a material that is sprayable but gels on contact with the skin surface. The manuscript reports the use of an engineered carrier device to deliver cells via spraying, to enhance retention upon a wound. The device involves shear-structuring of a gelling biopolymer, gellan, during the gelation process; forming a yield-stress fluid with shear-sensitive behaviours, known as a fluid gel. In this study, a formulation of gellan gum fluid gels are reported, formed with from 0.75 or 0.9% (w/v) polymer and varying the salt concentrations. The rheological properties and the propensity of the material to wet a surface were determined for polymer modified and non-polymer modified cell suspensions. The gellan fluid gels had a significantly higher viscosity and contact angle when compared to the non-polymer carrier. Viability of cells was not impeded by encapsulation in the gellan fluid gel or spraying. The shear thinning property of the material enabled it to be applied using an airbrush and spray angle, distance and air pressure were optimised for coverage and viability. Spray delivery of skin cells has successfully translated to clinical practice. However, it has not yet been widely accepted due to limited retention and disputable cell viability in the wound. Here, we report a method for delivering cells onto wound surfaces using a gellan-based shear-thinning gel system. The viscoelastic properties allow the material to liquefy upon spraying and restructure rapidly on the surface. Our results demonstrate reduced run-off from the surface compared to currently used low-viscosity cell carriers. Moreover, encapsulated cells remain viable throughout the process. Although this paper studies the encapsulation of one cell type, a similar approach could potentially be adopted for other cell types. 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Autologous cultured or uncultured cells are often delivered to the surface in saline-like suspensions. This delivery method is limited because droplets of the sprayed suspension form upon deposition and run across the wound bed, leading to uneven coverage and cell loss. One way to circumvent this problem would be to use a gel-based material to enhance surface retention. Fibrin systems have been explored as co-delivery system with keratinocytes or as adjunct to ‘seal’ the cells following spray delivery, but the high costs and need for autologous blood has impeded its widespread use. Aside from fibrin gel, which can exhibit variable properties, it has not been possible to develop a gel-based carrier that solidifies on the skin surface. This is because it is challenging to develop a material that is sprayable but gels on contact with the skin surface. The manuscript reports the use of an engineered carrier device to deliver cells via spraying, to enhance retention upon a wound. The device involves shear-structuring of a gelling biopolymer, gellan, during the gelation process; forming a yield-stress fluid with shear-sensitive behaviours, known as a fluid gel. In this study, a formulation of gellan gum fluid gels are reported, formed with from 0.75 or 0.9% (w/v) polymer and varying the salt concentrations. The rheological properties and the propensity of the material to wet a surface were determined for polymer modified and non-polymer modified cell suspensions. The gellan fluid gels had a significantly higher viscosity and contact angle when compared to the non-polymer carrier. Viability of cells was not impeded by encapsulation in the gellan fluid gel or spraying. The shear thinning property of the material enabled it to be applied using an airbrush and spray angle, distance and air pressure were optimised for coverage and viability. Spray delivery of skin cells has successfully translated to clinical practice. However, it has not yet been widely accepted due to limited retention and disputable cell viability in the wound. Here, we report a method for delivering cells onto wound surfaces using a gellan-based shear-thinning gel system. The viscoelastic properties allow the material to liquefy upon spraying and restructure rapidly on the surface. Our results demonstrate reduced run-off from the surface compared to currently used low-viscosity cell carriers. Moreover, encapsulated cells remain viable throughout the process. Although this paper studies the encapsulation of one cell type, a similar approach could potentially be adopted for other cell types. Our data supports further studies to confirm these results in in vivo models.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30904549</pmid><doi>10.1016/j.actbio.2019.03.036</doi><tpages>14</tpages></addata></record>
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subjects Administration, Topical
Autografts
Biopolymers
Cell suspensions
Cell transplantation
Cell viability
Clinical medicine
Contact angle
Drug Carriers - chemistry
Drug Carriers - pharmacology
Encapsulation
Fibrin
Fluid gel
Gelation
Gellan gum
Gels
Gels - chemistry
Gels - pharmacology
Humans
In vivo methods and tests
Keratinocytes
Keratinocytes - metabolism
Keratinocytes - pathology
Keratinocytes - transplantation
Polymers
Polysaccharides, Bacterial - chemistry
Polysaccharides, Bacterial - pharmacology
Properties (attributes)
Retention
Rheological properties
Runoff
Shear
Shear thinning (liquids)
Skin
Spray therapies
Spraying
Thinning
Transplantation
Viscoelasticity
Viscosity
Wounds
Yield-stress fluid
title A gellan-based fluid gel carrier to enhance topical spray delivery
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