Slow depressurization following intradiscal injection leads to injectate leakage in a large animal model

Abstract Needle injection has been indicated as the most practical method of delivering therapeutic agents to the intervertebral disc due to the disc's largely avascular nature. As the disc is characterized by both high stiffness and low permeability, injection requires substantial pressure, wh...

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Main Authors: Lara J. Varden, Duc T. Nguyen, Arthur J. Michalek
Format: Article
Language:English
Published: Wiley 2019-09-01
Series:JOR Spine
Subjects:
Online Access:https://doi.org/10.1002/jsp2.1061
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spelling doaj-c3a200aad7bc4080912dfacd7e8ac7e92020-11-25T02:39:33ZengWileyJOR Spine2572-11432019-09-0123n/an/a10.1002/jsp2.1061Slow depressurization following intradiscal injection leads to injectate leakage in a large animal modelLara J. Varden0Duc T. Nguyen1Arthur J. Michalek2Interdisciplinary Bioscience and Biotechnology Program Clarkson University Potsdam New YorkDepartment of Mechanical and Aeronautical Engineering Clarkson University Potsdam New YorkDepartment of Mechanical and Aeronautical Engineering Clarkson University Potsdam New YorkAbstract Needle injection has been indicated as the most practical method of delivering therapeutic agents to the intervertebral disc due to the disc's largely avascular nature. As the disc is characterized by both high stiffness and low permeability, injection requires substantial pressure, which may not relax on practical time scales. Additionally, needle puncture results in a localized disruption to the annulus fibrosus that can provide a leakage pathway for pressurized injectate. We hypothesized that intradiscal injection would result in slow relaxation of injectate pressure, followed by leakage upon needle retraction. This hypothesis was tested via controlled injection of fluorescently labeled saline into bovine caudal discs via a 21 gauge needle. Injections were performed with 10% of total disc volume injected at 3%/s followed by a 4‐minute dwell. An analytical poroelastic model was calibrated to the experimental data and used to estimate injectate delivery with time. Experimental results confirmed both pressurization (with a peak of 199 ± 45 kPa) and slow recovery (final pressure of 81 ± 23 kPa). Injectate leakage through the needle puncture was verified following needle retraction in all samples. Histological sections of the discs displayed a clear defect at each disc's injection site with strong fluorescent labeling indicating a leakage pathway. The modeling results suggest that less than one‐fourth of the injected volume was absorbed by the tissue in 4 minutes. Taken together these results suggest that needle injection is a feasible, albeit inefficient method for delivery of therapeutic agents into the intervertebral disc. Particular care should be taken to aspirate un‐absorbed injectate prior to needle retraction to prevent leakage and exposure of surrounding tissues.https://doi.org/10.1002/jsp2.10615‐DTAFbovine caudalintervertebral discneedle punctureporoelastic model
collection DOAJ
language English
format Article
sources DOAJ
author Lara J. Varden
Duc T. Nguyen
Arthur J. Michalek
spellingShingle Lara J. Varden
Duc T. Nguyen
Arthur J. Michalek
Slow depressurization following intradiscal injection leads to injectate leakage in a large animal model
JOR Spine
5‐DTAF
bovine caudal
intervertebral disc
needle puncture
poroelastic model
author_facet Lara J. Varden
Duc T. Nguyen
Arthur J. Michalek
author_sort Lara J. Varden
title Slow depressurization following intradiscal injection leads to injectate leakage in a large animal model
title_short Slow depressurization following intradiscal injection leads to injectate leakage in a large animal model
title_full Slow depressurization following intradiscal injection leads to injectate leakage in a large animal model
title_fullStr Slow depressurization following intradiscal injection leads to injectate leakage in a large animal model
title_full_unstemmed Slow depressurization following intradiscal injection leads to injectate leakage in a large animal model
title_sort slow depressurization following intradiscal injection leads to injectate leakage in a large animal model
publisher Wiley
series JOR Spine
issn 2572-1143
publishDate 2019-09-01
description Abstract Needle injection has been indicated as the most practical method of delivering therapeutic agents to the intervertebral disc due to the disc's largely avascular nature. As the disc is characterized by both high stiffness and low permeability, injection requires substantial pressure, which may not relax on practical time scales. Additionally, needle puncture results in a localized disruption to the annulus fibrosus that can provide a leakage pathway for pressurized injectate. We hypothesized that intradiscal injection would result in slow relaxation of injectate pressure, followed by leakage upon needle retraction. This hypothesis was tested via controlled injection of fluorescently labeled saline into bovine caudal discs via a 21 gauge needle. Injections were performed with 10% of total disc volume injected at 3%/s followed by a 4‐minute dwell. An analytical poroelastic model was calibrated to the experimental data and used to estimate injectate delivery with time. Experimental results confirmed both pressurization (with a peak of 199 ± 45 kPa) and slow recovery (final pressure of 81 ± 23 kPa). Injectate leakage through the needle puncture was verified following needle retraction in all samples. Histological sections of the discs displayed a clear defect at each disc's injection site with strong fluorescent labeling indicating a leakage pathway. The modeling results suggest that less than one‐fourth of the injected volume was absorbed by the tissue in 4 minutes. Taken together these results suggest that needle injection is a feasible, albeit inefficient method for delivery of therapeutic agents into the intervertebral disc. Particular care should be taken to aspirate un‐absorbed injectate prior to needle retraction to prevent leakage and exposure of surrounding tissues.
topic 5‐DTAF
bovine caudal
intervertebral disc
needle puncture
poroelastic model
url https://doi.org/10.1002/jsp2.1061
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