Thermoreversible hydrogels as a Drug Release Platform in Degenerative Disc Disease

Marloes L.P. Langelaan1, Renz van Ee1, Klaas Timmer1, Linda M. Kock2, Audrey Petit3, Hsiao-Yin Yang4, Ruud Licht4, Jacco Eversdijk1, Keita Ito2, Mike de Leeuw3, Laura Creemers4, and Nicole E. Papen-Botterhuis1
1TNO, Eindhoven, The Netherlands; 2Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands; 3InGell Labs BV, Groningen, The Netherlands; 4UMCU, Utrecht, The Netherlands

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Summary
For the treatment of degenerative disc disease (DDD) via injections in the nucleus pulposus, novel hydrogels were prepared with Layered Double Hydroxide (LDH) suspensions and pNIPAAM. These LDH suspensions were synthesized in a reproducible way and were degradable in PBS at 37°C. The hydrogels showed no shrinkage and measured complex moduli were around 1kPa at 37°C. Sterilization by gamma-radiation showed no negative effects on gel formation and very little cytotoxicity was found by in vitro cell tests. The hydrogels have successfully been loaded with the compound celecoxib and showed a release profile of this compound in time. Furthermore we investigated the effects of controlled release vs. a bolus injection of the drug in vitro in a 3D tissue engineered cartilage model system. Controlled release of celecoxib caused complete inhibition of PGE2 over the entire culture period (28 days), whereas the bolus injection inhibited PGE2 production up to 11 days.

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