Imparting bioadhesive properties to injectable hydrogels for nucleus pulposus treatment and augmentation

Erik C. Brewer

doi:10.17918/etd-2663

Degenerative Disc disease (DDD) is a disorder of the intervertebral disc resulting from a dehydrated nucleus pulposus. Current treatment methods for have had mixed long-term results and possibly promote further degeneration. In the early-stages of DDD, a simpler and less-invasive procedure would be to augment only the nucleus pulposus while leaving the rest of the disc intact. Hydrogels have high potential to serve as prosthetic material due to their mechanical and physiological similarities to tissue. Hydrogels exhibiting lower critical phase separation, such as poly(N-isopropylacrylamide) (PNIPAAm), have the unique ability to transition from a free-flowing aqueous solution to a hardened gel in vivo, allowing them to be injected rather than surgically inserted into the spine. Imparting bioadhesive properties to these hydrogels would help create a cohesive nucleus/hydrogel network and prevent further migration or expulsion from the disc segments. Adhesive properties can be created by blending hydrogels with poly(ethylenimine) (PEI), a cationic, branched polymer followed by treatment of a crosslinking agent, glutaraldehyde. The reaction bridges amine groups in PEI with other PEI chains in addition to the collagen proteins found in native tissue, creating an adhesive bond. Adhesion tests showed that hydrogel/PEI blends were capable of producing bonds up to 302.8 ± 41.2 kPa in strength. Bond strength was found to increase with increasing PEI chain length, though decrease with increasing PEI concentration. Release studies revealed that blends with higher PEI concentrations released less PEI during the phase separation, thus allowing less to adhere to tissue and weaker bonds to form. Though PEI and glutaraldehyde treatment have affected the mechanical properties of hydrogels in past studies, the addition of PEI and glutaraldehyde had minimal influence on the mechanical properties of the hydrogels used in this study. Treatment methods used in this study proved ineffective in a simulated nucleus pulposus injection. Glutaraldehyde injected into a hydrogel that had undergone phase separation was unable to diffuse to the hydrogel/tissue surface. Methods replicating epoxy adhesive systems, where two separate components are injected and mixed simultaneously, broke down the three-dimensional hydrogel network due to the instantaneous speed of the PEI/glutaraldehyde reaction compared to the rate of the phase transition. Future studies should focus on more advanced glutaraldehyde delivery methods.

Imparting bioadhesive properties to injectable hydrogels for nucleus pulposus treatment and augmentation

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Imparting bioadhesive properties to injectable hydrogels for nucleus pulposus treatment and augmentation

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