A collagen/alginate tissue-engineered Intervertebral disc for cervical total disc replacement - An in vivo study with dogs

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Disc degeneration in the cervical spine is a prevalent clinical predicament requiring surgery. Anterior cervical decompression and fusion, the commonly performed surgical procedure, poses risks for pseudoarthrosis and adjacent segment disease. Prosthetic total disc replacement devices have therefore been developed to maintain segmental mobility, but have failed to replicate the native characteristics of the normal IVD in respect to motion, stability, load bearing properties, and mechanical damping. As an alternative treatment, we have pioneered a tissue-engineered IVD (TE-IVD) using collagen and alginate constructs seeded with anulus fibrosus and nucleus pulposus cells. Our initial in vivo rat-tail spine study showed that the TE-IVD successfully integrated with host tissue, reaching analogous biochemical, biomechanical, and histological properties as the native IVD. Further, a 2-month in vivo pilot study was conducted on the beagle cervical spine model; dogs are an ideal translational model due to similarity in anatomical and biomechanical features of the human spine. Our implanted TE-IVDs remained viable in the disc space, engrafted into the host tissue, and partially maintained disc height. Few dogs even presented gradual maturation of the TE-IVD. Despite its promise, our study requires a long-term follow-up with sufficient sample size and an assessment of mechanical functionality of the treated discs. Further, due to the mechanical loading inherent in the beagle spine, disc height of treated segments was only 70% of that of healthy discs; the need for stiffer TE-IVDs is of concern. We recently discovered that TE-IVD stiffness can be significantly enhanced with in vitro mechanical conditioning at its cultivation. Mechanically loaded TE-IVDs may meet the higher requisite of a mobile spine segment, yielding better implant viability and segment functionality. In the present study, we will evaluate mechanically conditioned TE-IVDs implanted in 12 beagles that will undergo discectomy at both C3/4 and 4/5. A total of 24 experimental disc segments will be split into three groups: a) 8 solely discectomized control, b) 8 discs treated with unloaded or c) 8 mechanically loaded TE-IVDs. Qualitative and quantitative X-ray and MRI analyses will be conducted at 8, 16, and 24 weeks to monitor degenerative changes and progress of implanted disc growth. After 24 weeks, motion segments will be histologically and biomechanically assessed.