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Annular Repair Using High-Density Collagen Gel: A Rat-Tail In Vivo Model

Grunert, Peter MD*; Borde, Brandon H. BS; Hudson, Katherine D. BS; Macielak, Michael R. BS*; Bonassar, Lawrence J. PhD†,‡; Härtl, Roger MD*

doi: 10.1097/BRS.0000000000000103
Basic Science

Study Design. Animal in vivo study.

Objective. To test the capability of high-density collagen gel to repair annular defects.

Summary of Background Data. Annular defects are associated with spontaneous disc herniations and disc degeneration, which can lead to significant morbidity. Persistent annular defects after surgical discectomies can increase reherniation rates. Several synthetic and biological materials have been developed for annular repair. This is the first study to test an injectable biomaterial in vivo.

Methods. We punctured caudal intervertebral discs in 42 athymic rats, using an 18-gauge needle to create an annular defect. High-density collagen (HDC), either alone or cross-linked with riboflavin (RF), was injected into the defect. There were 4 separate study groups: HDC, HDC cross-linked with either 0.25 mM RF or 0.50 mM RF, and a negative control that was punctured and not treated. The animals were followed for 5 weeks; radiographs were used to assess disc heights and magnetic resonance images were used to evaluate degenerative changes. We developed an algorithm on the basis of T2-relaxation time measurements to assess the size of the nucleus pulposus. Tails were collected for histological analysis to evaluate disc degeneration and measure the cross-sectional area of the nucleus pulposus.

Results. After 5 weeks, the control and the uncross-linked HDC groups both showed signs of progressive degenerative changes with minimal or no residual nucleus pulposus tissue in the disc space. Cross-linking significantly improved the ability of HDC gels to repair annular defects. The 0.50 mM RF cross-linked group showed only a slight decrease in nuclear tissue when compared with healthy discs, with no signs of intervertebral disc (IVD) degeneration. The annulus fibrosus was partially repaired by a fibrous cap that bridged the defect. Host fibroblasts infiltrated and remodeled the injected collagen.

Conclusion. HDC is capable of repairing annular defects induced by needle puncture. The stiffness of HDC can be modified by riboflavin cross-linking and seems to positively affect the repair mechanism. These results need to be replicated in a larger animal model.

Level of Evidence: N/A

Annular defects are associated with degenerative changes of intervertebral discs. This is the first study to test an injectable biomaterial for annular repair in vivo. High-density collagen was capable of repairing annular defects in a needle puncture rat-tail model. Riboflavin fiber cross-linking enhanced the repair mechanism.

*Department of Neurological Surgery, Weill Cornell Brain and Spine Institute, Weill Cornell Medical College, New York, NY;

Department of Biomedical Engineering, Cornell University, Ithaca, NY; and

Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY.

Address correspondence and reprint requests to Roger Härtl, MD, Department of Neurological Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68th St, Box 99, New York, NY 10065; E-mail:

Acknowledgment date: July 2, 2013. Revised date: September 27, 2013. Acceptance date: October 21, 2013.

The manuscript submitted does not contain information about medical device(s)/drug(s).

AO Research Fund grant F-08-10B, the AOSpine International Hansjörg Wyss Focus Award 2010, and a grant from NFL Medical Charities funds were received to support this work.

Relevant financial activities outside the submitted work: grants.

© 2014 by Lippincott Williams & Wilkins