A collagen/alginate tissue-engineered Intervertebral disc for cervical total disc replacement - An in vivo study with dogs
Final Report Abstract
Here we demonstrate the efficacy of TE-IVDs in the canine cervical spine. TE-IVD components were constructed using adult canine annulus fibrosis and nucleus pulposus cells seeded into collagen and alginate hydrogels, respectively. Seeded gels were formed into a single disc unit using molds designed from the geometry of the canine spine. Stably implanted TE-IVDs demonstrated significant retention of disc height and physiological hydration compared to discectomy control. Both 4-week and 16-week histological assessments demonstrated chondrocytic cells surrounded by proteoglycan-rich matrices in the NP and by fibrocartilaginous matrices in the AF portions of implanted TE-IVDs. Integration into host tissue was confirmed over 16 weeks without any signs of immune reaction. Despite the significant biomechanical demands of the beagle cervical spine, our stably implanted TE-IVDs maintained their position, structure and hydration as well as disc height over 16 weeks in vivo. Our experiment employing stand-alone TE-IVD implantation under this clinically relevant model gave a fresh insight into development of biological disc treatment. First, mechanical stress causes instability and displacement of the implant. As evidenced by prosthetic TDR (48), displacement of implant is an arising complication when positioned in a fixation-free fashion, predominantly due to the human spine yielding severe axial loading. However, all the TE-IVDs at the C3/4 segment were stable in our study and maintained disc height up to 70 % of adjacent normal discs. Biomechanics are known to be different among different levels of the cervical spine (49) and our findings may suggest biomechanics at this level of the beagle spine are more favorable to the biological disc implantation. The follow-up study showed that a bio-resorbable plate can be used in combination with a TE-IVD to help stabilize a canine cervical motion segment, while allowing load sharing to the TE-IVD. Implantation of the TE-IVD in the disc space by itself resulted in relatively similar mechanical properties to those of the discectomized segments suggesting low magnitudes of loads are shared by the construct. The significant increase in mechanical properties of the motion segment with a plate suggests that the BSS increases the stability of TE-IVD construct and helps reduce implant displacement outside of the disc space. Due to the unique anatomy of the canine cervical spine, we decided to utilize swine cervical spines for our next biomechanical studies since they seem to me be more similar anatomically compared to human cervical spines.
Publications
- (2017) Elimination of Subsidence with 26-mm-Wide Cages in Extreme Lateral Interbody Fusion. World neurosurgery 104 644–652
Lang, Gernot; Navarro-Ramirez, Rodrigo; Gandevia, Lena; Hussain, Ibrahim; Nakhla, Jonathan; Zubkov, Micaella; Härtl, Roger
(See online at https://doi.org/10.1016/j.wneu.2017.05.035) - (2017) Potential and Limitations of Neural Decompression in Extreme Lateral Interbody Fusion-A Systematic Review. World neurosurgery 101 99–113
Lang, Gernot; Perrech, Moritz; Navarro-Ramirez, Rodrigo; Hussain, Ibrahim; Pennicooke, Brenton; Maryam, Farah; Avila, Mauricio J.; Härtl, Roger
(See online at https://doi.org/10.1016/j.wneu.2017.01.080) - Summary of Clinical Trials with Biological Treatment Approaches for Spinal Disease. Biological Approaches to Spinal Disc Repair and Regeneration for Clinicians. Thieme 2017
Lang G, Hussain I, Pennicooke B, Moriguchi Y, Härtl R
(See online at https://dx.doi.org/10.1055/b-0037-145102)