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

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 n...

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Detalles Bibliográficos
Autores principales: Varden, Lara J., Nguyen, Duc T., Michalek, Arthur J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764785/
https://www.ncbi.nlm.nih.gov/pubmed/31572978
http://dx.doi.org/10.1002/jsp2.1061
Descripción
Sumario: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.