Hydrogels Found Not Effective for Disc Regeneration
Introduction: In this study, two types of hydrogels for nucleus replacement were investigated in an ovine nucleotomy model: 1) hydrogels functionalized with anti-angiogenic peptides, and 2) seeded with bone marrow derived mononuclear cells (BMC). The study was designed to investigate the effects of the hydrogels on range of motion, disc height, and progression of intervertebral disc degeneration.
Methods: Twenty-four sheep (age, 2-4.5 years; weight, 76-108 kg) were implanted with four different hydrogel configurations:
- Hydrogels made of ionically crosslinked metacrylated gellan gum hydrogels (iGG-MA)
- Hydrogels made of iGG-MA functionalized with non-cytotoxic polylysine-based vascular endothelial growth factor blockers (VEGF-blockers)
- Hydrogels made of dodecyl-amide of hyaluronic acid (DDAHA)
- Hydrogels made of DDAHA and seeded with autologous BMC
The implantations required opening the annulus and nucleotomy to allow space for hydrogel placement. Untreated nucleotomy discs served as controls. Histological and biomechanical tests were conducted at 12 weeks.
Results: The hydrogels did not show improvement on biomechanical tests and were not able to restore disc height compared to nucleotomy controls. The latter finding suggests extrusion of the hydrogels out of the disc space, the authors noted. Implanted discs showed a smaller range of motion and more signs of degeneration than intact discs. There was a trend toward a slower degree of deterioration with BMC-seeded discs from 6 to 12 weeks.
Conclusion: The hydrogel configurations used in this study did not regenerate biofunctionality of intervertebral discs, possibly because of hydrogel extrusion. The authors speculate that development of annulus sealants that prevent hydrogel extrusion may allow for biological disc regeneration and restoration of intervertebral disc functionality.
This paper, which examines the use of hydrogels combined with either bone marrow derived mononuclear cells (BMC) or anti-angiogenic peptides for the possible use in intervertebral disc regeneration/replacement, is unique in that the authors report a negative result.
A number of salient considerations for the negative outcome from this paper should be considered.
• First, although two types of hydrogels are used, the authors do not clearly state why these two types were chosen. It may have been better to use one hydrogel in order to limit the number of variables in this study.
• Secondly, the anti-angiogenic peptide was combined with one of the hydrogels, but it would have been interested to see the peptide combined with both the hydrogel and BMC.
• Third, as the authors pointed out, one of the main disadvantages of the hydrogels is the need to create both an annular and disc defect, which then requires a sealant to keep the hydrogel from extruding.
• Finally, the time period of 12 weeks might have been too short to allow for the various preparations to have an effect.
In conclusion, the authors pointed out that perhaps the main reason for the negative results stems from extrusion of the hydrogel from the intervertebral disc and that a better sealant is needed for hydrogels to be an effective intervertebral disc nucleus replacement.