Research Papers

Evaluation of an In Situ Gelable and Injectable Hydrogel Treatment to Preserve Human Disc Mechanical Function Undergoing Physiologic Cyclic Loading Followed by Hydrated Recovery

[+] Author and Article Information
Brent L. Showalter

Department of Bioengineering,
University of Pennsylvania,
424 Stemmler, 36th and Hamilton Walk,
Philadelphia, PA 19104

Dawn M. Elliott

Department of Biomedical Engineering,
University of Delaware,
161 Colburn,
150 Academy Street,
Newark, DE 19716

Weiliam Chen

Endomedix, Inc.,
Enterprise Development Center,
New Jersey Institute of Technology,
211 Warren Street,
Newark, NJ 07103

Neil R. Malhotra

Department of Neurosurgery,
University of Pennsylvania,
3 Silverstein Pavilion,
3400 Spruce Street,
Philadelphia, PA 19104
e-mail: Neil.malhotra@uphs.upenn.edu

1Corresponding author.

Manuscript received July 21, 2014; final manuscript received April 27, 2015; published online June 16, 2015. Assoc. Editor: Sean S. Kohles.

J Biomech Eng 137(8), 081008 (Aug 01, 2015) (7 pages) Paper No: BIO-14-1334; doi: 10.1115/1.4030530 History: Received July 21, 2014; Revised April 27, 2015; Online June 16, 2015

Despite the prevalence of disc degeneration and its contributions to low back problems, many current treatments are palliative only and ultimately fail. To address this, nucleus pulposus replacements are under development. Previous work on an injectable hydrogel nucleus pulposus replacement composed of n-carboxyethyl chitosan, oxidized dextran, and teleostean has shown that it has properties similar to native nucleus pulposus, can restore compressive range of motion in ovine discs, is biocompatible, and promotes cell proliferation. The objective of this study was to determine if the hydrogel implant will be contained and if it will restore mechanics in human discs undergoing physiologic cyclic compressive loading. Fourteen human lumbar spine segments were tested using physiologic cyclic compressive loading while intact, following nucleotomy, and again following treatment of injecting either phosphate buffered saline (PBS) (sham, n = 7) or hydrogel (implant, n = 7). In each compressive test, mechanical parameters were measured immediately before and after 10,000 cycles of compressive loading and following a period of hydrated recovery. The hydrogel implant was not ejected from the disc during 10,000 cycles of physiological compression testing and appeared undamaged when discs were bisected following all mechanical tests. For sham samples, creep during cyclic loading increased (+15%) from creep during nucleotomy testing, while for implant samples creep strain decreased (−3%) toward normal. There was no difference in compressive modulus or compressive strains between implant and sham samples. These findings demonstrate that the implant interdigitates with the nucleus pulposus, preventing its expulsion during 10,000 cycles of compressive loading and preserves disc creep within human L5–S1 discs. This and previous studies provide a solid foundation for continuing to evaluate the efficacy of the hydrogel implant.

Copyright © 2015 by ASME
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Fig. 1

T2 relaxation times are strongly correlated to Pfirrmann scores for the human L5–S1 discs used in this study

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Fig. 2

The mechanical testing procedure altered disc hydration. Discs are fully hydrated in a PBS bath containing protease inhibitors (steps 1 and 5), and have reduced hydration after cyclic loading (step 3). Mechanical parameters are measured after each change in hydration level (steps 2, 4, and 6).

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Fig. 3

Mechanical parameters are found using a trilinear fit of force–displacement curve from 50th cycle of the mechanical measurement steps (steps 2, 4, and 6 of the testing procedure). The compression loading curve (diamonds) is separated from the data. Compression range of motion is the displacement between 0 and 0.48 MPa on the compression loading curve. Compression stiffness is the slope of the line fit through 0.38 and 0.48 MPa. Compressive stiffness and range of motion are then normalized by intact disc area and height.

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Fig. 4

Bisected human L5–S1 disc after complete mechanical test, including 10,000 cycles of compressive loading. The hydrogel implant stayed intact within the disc, although some of the toluidine blue used to dye the gel leached into the surrounding disc tissue. The enlarged region shows that the implant (dark region in lower left corner of inset) filled in the irregular contours of the remaining nucleus pulposus (light region of inset).

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Fig. 5

Cyclic loading caused an increase in compression modulus (a) and compression strain (b) for both sham and implant samples. These increases were recovered following a period of overnight hydration, indicating that the changes are due to changes in hydration distribution within the intervertebral disc. Recoverable increases in compression modulus and strain are consistent with trends in intact and nucleotomy samples. Data presented as mean + standard error (* indicates p < 0.05).

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Fig. 6

Nucleotomy increased creep strain (a). Following treatment, strain continued to increase for sham samples, but decreased for implant samples (b). Data presented as mean + standard error (* indicates p < 0.05).

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Fig. 7

Percent change from nucleotomy values for sham and implant samples. Treatment caused no change in compression modulus (a). Compression strain continued to increase for both sham and implant samples at the cyclic and recovery time points (b). Data presented as mean + standard error (+ indicates p < 0.05 versus nucleotomy values).

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Fig. 8

Percent change in compression modulus between the initial and cyclic time point for the samples in the implant group. This correlation was not significant for the samples while they were intact or following nucleotomy, but was significant following injection of the hydrogel. The slope (m) and y-intercepts (b) of the regression are show in the legend.




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