Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing

Antisense oligodeoxynucleotides targeting the mRNA of the gap junction protein Cx43 promote tissue repair in a variety of different wounds. Delivery of the antisense drug has most often been achieved by a thermoreversible hydrogel, Pluronic F-127, which is very effective in the short term but does n...

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Main Authors: Gilmartin, Daniel J., Soon, Allyson, Thrasivoulou, Christopher, Phillips, Anthony R. J., Jayasinghe, Suwan N., Becker, David Lawrence
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Journal Article
Language:English
Published: 2016
Subjects:
Online Access:https://hdl.handle.net/10356/83373
http://hdl.handle.net/10220/41421
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author Gilmartin, Daniel J.
Soon, Allyson
Thrasivoulou, Christopher
Phillips, Anthony R. J.
Jayasinghe, Suwan N.
Becker, David Lawrence
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Gilmartin, Daniel J.
Soon, Allyson
Thrasivoulou, Christopher
Phillips, Anthony R. J.
Jayasinghe, Suwan N.
Becker, David Lawrence
author_sort Gilmartin, Daniel J.
collection NTU
description Antisense oligodeoxynucleotides targeting the mRNA of the gap junction protein Cx43 promote tissue repair in a variety of different wounds. Delivery of the antisense drug has most often been achieved by a thermoreversible hydrogel, Pluronic F-127, which is very effective in the short term but does not allow for sustained delivery over several days. For chronic wounds that take a long time to heal, repeated dosing with the drug may be desirable but is not always compatible with conventional treatments such as the weekly changing of compression bandages on venous leg ulcers. Here the coating of collagen scaffolds with antisense oligonucleotides is investigated and a way to provide protection of the oligodeoxynucleotide drug is found in conjunction with sustained release over a 7 d period. This approach significantly reduces the normal foreign body reaction to the scaffold, which induces an increase of Cx43 protein and an inhibition of healing. As a result of the antisense integration into the scaffold, inflammation is reduced with the rate of wound healing and contracture is significantly improved. This coated scaffold approach may be very useful for treating venous leg ulcers and also for providing a sustained release of any other types of oligonucleotide drugs that are being developed.
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spelling ntu-10356/833732021-03-10T02:50:20Z Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing Gilmartin, Daniel J. Soon, Allyson Thrasivoulou, Christopher Phillips, Anthony R. J. Jayasinghe, Suwan N. Becker, David Lawrence Lee Kong Chian School of Medicine (LKCMedicine) Lee Kong Chian School of Medicine Tissue Repair Oligonucleotide Delivery Antisense oligodeoxynucleotides targeting the mRNA of the gap junction protein Cx43 promote tissue repair in a variety of different wounds. Delivery of the antisense drug has most often been achieved by a thermoreversible hydrogel, Pluronic F-127, which is very effective in the short term but does not allow for sustained delivery over several days. For chronic wounds that take a long time to heal, repeated dosing with the drug may be desirable but is not always compatible with conventional treatments such as the weekly changing of compression bandages on venous leg ulcers. Here the coating of collagen scaffolds with antisense oligonucleotides is investigated and a way to provide protection of the oligodeoxynucleotide drug is found in conjunction with sustained release over a 7 d period. This approach significantly reduces the normal foreign body reaction to the scaffold, which induces an increase of Cx43 protein and an inhibition of healing. As a result of the antisense integration into the scaffold, inflammation is reduced with the rate of wound healing and contracture is significantly improved. This coated scaffold approach may be very useful for treating venous leg ulcers and also for providing a sustained release of any other types of oligonucleotide drugs that are being developed. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version 2016-09-06T05:37:38Z 2019-12-06T15:21:02Z 2016-09-06T05:37:38Z 2019-12-06T15:21:02Z 2016 Journal Article Gilmartin, D. J., Soon, A., Thrasivoulou, C., Phillips, A. R. J., Jayasinghe, S. N., & Becker, D. L. (2016). Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing. Advanced Healthcare Materials, 5(14), 1786-1799. 2192-2640 https://hdl.handle.net/10356/83373 http://hdl.handle.net/10220/41421 10.1002/adhm.201600175 en Advanced Healthcare Materials © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the author created version of a work that has been peer reviewed and accepted for publication by Advanced Healthcare Materials, WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1002/adhm.201600175]. 35 p. application/pdf
spellingShingle Tissue Repair
Oligonucleotide Delivery
Gilmartin, Daniel J.
Soon, Allyson
Thrasivoulou, Christopher
Phillips, Anthony R. J.
Jayasinghe, Suwan N.
Becker, David Lawrence
Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing
title Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing
title_full Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing
title_fullStr Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing
title_full_unstemmed Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing
title_short Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing
title_sort sustained release of cx43 antisense oligodeoxynucleotides from coated collagen scaffolds promotes wound healing
topic Tissue Repair
Oligonucleotide Delivery
url https://hdl.handle.net/10356/83373
http://hdl.handle.net/10220/41421
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