2017•PLoS ONEOpen access

Total disc replacement using tissue-engineered intervertebral discs in the canine cervical spine

Yu Moriguchi, Jorge Mojica-Santiago, Peter Grunert, Brenton Henry Pennicooke, Connor Berlin, Thamina Khair, Rodrigo Navarro-Ramírez, Rodolfo J Ricart Arbona, Joseph Nguyen, Roger Härtl, Lawrence J. Bonassar

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Abstract

The most common reason that adults in the United States see their physician is lower back or neck pain secondary to degenerative disc disease. To date, approaches to treat degenerative disc disease are confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Tissue engineered intervertebral discs (TE-IVDs) have been proposed as an alternative approach and have shown promise in replacing native IVD in the rodent tail spine. Here we demonstrate the efficacy of our 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. Skeletally mature beagles underwent discectomy with whole IVD resection at levels between C3/4 and C6/7, and were then divided into two groups that received only discectomy or discectomy followed by implantation of TE-IVD. 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.

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The most common reason that adults in the United States see their physician is lower back or neck pain secondary to degenerative disc disease. To date, approaches to treat degenerative disc disease are confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Tissue engineered intervertebral discs (TE-IVDs) have been proposed as an alternative approach and have shown promise in replacing native IVD in the rodent tail spine. Here we demonstrate the efficacy of our 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. Skeletally mature beagles underwent discectomy with whole IVD resection at levels between C3/4 and C6/7, and were then divided into two groups that received only discectomy or discectomy followed by implantation of TE-IVD. 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.

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Available abstract

The most common reason that adults in the United States see their physician is lower back or neck pain secondary to degenerative disc disease. To date, approaches to treat degenerative disc disease are confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Tissue engineered intervertebral discs (TE-IVDs) have been proposed as an alternative approach and have shown promise in replacing native IVD in the rodent tail spine. Here we demonstrate the efficacy of our 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. Skeletally mature beagles underwent discectomy with whole IVD resection at levels between C3/4 and C6/7, and were then divided into two groups that received only discectomy or discectomy followed by implantation of TE-IVD. 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.

Key concepts: Discectomy, Intervertebral disc, Degenerative disc disease, Beagle, Medicine, Cervical spine, Intervertebral disk, Anatomy

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