Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation

Severe pathoanatomical and mechanical injuries compromise patient recovery and survival following penetrating brain injury (PBI). The realization that the blood–brain barrier (BBB) plays a major role in dictating post-PBI events has led to rising interests in possible therapeutic interventions throu...

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Main Authors: Choy, David Kim Seng, Nyein, Mya Aye, Lu, Jia, Nga, Vincent Diong Weng, Lim, Jing, Chou, Ning, Yeo, Tseng Tsai, Teoh, Swee-Hin
Other Authors: School of Chemical and Biomedical Engineering
Format: Journal Article
Language:English
Published: 2015
Subjects:
Online Access:https://hdl.handle.net/10356/106998
http://hdl.handle.net/10220/25229
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author Choy, David Kim Seng
Nyein, Mya Aye
Lu, Jia
Nga, Vincent Diong Weng
Lim, Jing
Chou, Ning
Yeo, Tseng Tsai
Teoh, Swee-Hin
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Choy, David Kim Seng
Nyein, Mya Aye
Lu, Jia
Nga, Vincent Diong Weng
Lim, Jing
Chou, Ning
Yeo, Tseng Tsai
Teoh, Swee-Hin
author_sort Choy, David Kim Seng
collection NTU
description Severe pathoanatomical and mechanical injuries compromise patient recovery and survival following penetrating brain injury (PBI). The realization that the blood–brain barrier (BBB) plays a major role in dictating post-PBI events has led to rising interests in possible therapeutic interventions through the BBB. Recently, the choroid plexus has also been suggested as a potential therapeutic target. The use of biocompatible scaffolds for the delivery of therapeutic agents, but little is known about their interaction with cerebral tissue, which has important clinical implications. Therefore, the authors have sought to investigate the effect of polycaprolactone (PCL) and PCL/tricalcium phosphate (PCL/TCP) scaffolds on the maintenance of BBB phenotype posttraumatic brain injury. Cranial defects of 3 mm depth were created in Sprague Dawley rats, and PCL and PCL/TCP scaffolds were subsequently implanted in predetermined locations for a period of 1 week and 1 month. Higher endothelial barrier antigen (EBA) expressions from PCL-based scaffold groups (p>0.05) were found, suggesting slight advantages over the sham group (no scaffold implantation). PCL/TCP scaffold group also expressed EBA to a higher degree (p>0.05) than PCL scaffolds. Importantly, higher capillary count and area as early as 1 week postimplantation suggested lowered ischemia from the PCL/TCP scaffold group as compared with PCL and sham. Evaluation of interlukin-1β expression suggested that the PCL and PCL/TCP scaffolds did not cause prolonged inflammation. BBB transport selectivity was evaluated by the expression of aquaporin-4 (AQP-4). Attenuated expression of AQP-4 in the PCL/TCP group (p<0.05) suggested that PCL/TCP scaffolds altered BBB selectivity to a lower degree as compared with sham and PCL groups, pointing to potential clinical implications in reducing cerebral edema. Taken together, the responses of PCL-based scaffolds with brain tissue suggested safety, and encourages further preclinical evaluation in PBI management with these scaffolds.
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spelling ntu-10356/1069982023-12-29T06:48:18Z Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation Choy, David Kim Seng Nyein, Mya Aye Lu, Jia Nga, Vincent Diong Weng Lim, Jing Chou, Ning Yeo, Tseng Tsai Teoh, Swee-Hin School of Chemical and Biomedical Engineering DRNTU::Science::Medicine::Tissue engineering Severe pathoanatomical and mechanical injuries compromise patient recovery and survival following penetrating brain injury (PBI). The realization that the blood–brain barrier (BBB) plays a major role in dictating post-PBI events has led to rising interests in possible therapeutic interventions through the BBB. Recently, the choroid plexus has also been suggested as a potential therapeutic target. The use of biocompatible scaffolds for the delivery of therapeutic agents, but little is known about their interaction with cerebral tissue, which has important clinical implications. Therefore, the authors have sought to investigate the effect of polycaprolactone (PCL) and PCL/tricalcium phosphate (PCL/TCP) scaffolds on the maintenance of BBB phenotype posttraumatic brain injury. Cranial defects of 3 mm depth were created in Sprague Dawley rats, and PCL and PCL/TCP scaffolds were subsequently implanted in predetermined locations for a period of 1 week and 1 month. Higher endothelial barrier antigen (EBA) expressions from PCL-based scaffold groups (p>0.05) were found, suggesting slight advantages over the sham group (no scaffold implantation). PCL/TCP scaffold group also expressed EBA to a higher degree (p>0.05) than PCL scaffolds. Importantly, higher capillary count and area as early as 1 week postimplantation suggested lowered ischemia from the PCL/TCP scaffold group as compared with PCL and sham. Evaluation of interlukin-1β expression suggested that the PCL and PCL/TCP scaffolds did not cause prolonged inflammation. BBB transport selectivity was evaluated by the expression of aquaporin-4 (AQP-4). Attenuated expression of AQP-4 in the PCL/TCP group (p<0.05) suggested that PCL/TCP scaffolds altered BBB selectivity to a lower degree as compared with sham and PCL groups, pointing to potential clinical implications in reducing cerebral edema. Taken together, the responses of PCL-based scaffolds with brain tissue suggested safety, and encourages further preclinical evaluation in PBI management with these scaffolds. Published version 2015-03-11T06:13:55Z 2019-12-06T22:22:47Z 2015-03-11T06:13:55Z 2019-12-06T22:22:47Z 2015 2015 Journal Article Nga, V. D. W., Lim, J., Choy, D. K. S., Nyein, M. A., Lu, J., Chou, N., et al. (2015). Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation. Tissue engineering part A, 21(3-4), 647-653. 1937-3341 https://hdl.handle.net/10356/106998 http://hdl.handle.net/10220/25229 10.1089/ten.tea.2013.0779 25335965 en Tissue engineering part A © 2015 Mary Ann Liebert. This paper was published in Tissue Engineering Part A and is made available as an electronic reprint (preprint) with permission of Mary Ann Liebert. The paper can be found at the following official DOI: [http://dx.doi.org/10.1089/ten.tea.2013.0779].  One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. 7 p. application/pdf
spellingShingle DRNTU::Science::Medicine::Tissue engineering
Choy, David Kim Seng
Nyein, Mya Aye
Lu, Jia
Nga, Vincent Diong Weng
Lim, Jing
Chou, Ning
Yeo, Tseng Tsai
Teoh, Swee-Hin
Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation
title Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation
title_full Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation
title_fullStr Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation
title_full_unstemmed Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation
title_short Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation
title_sort effects of polycaprolactone based scaffolds on the blood brain barrier and cerebral inflammation
topic DRNTU::Science::Medicine::Tissue engineering
url https://hdl.handle.net/10356/106998
http://hdl.handle.net/10220/25229
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