Introduction: Total disc replacement using tissue-engineered intervertebral discs (TE-IVD) offers an alternative biological treatment option for degenerative disc disease. Our group has previously developed a unique TE-IVD that demonstrated efficacy in maintaining disc height, physiological hydration, and tissue integration in beagle models in vivo. However, biomechanical properties were inferior to native IVD and implant displacement occurred in several cases. We now investigate the biomechanical responses of our TE-IVDs combined with an anterior bio-resorbable stabilization system (BSS) in an ex vivo canine cervical spine model (Figure 1A-B).
Methods: Using techniques previously described (1,2), TE-IVDs with an inner nucleus pulposus cell-laden alginate layer surrounded by an outer annulus fibrosus cell-laden collagen layer were developed. Cervical spine motion segments (N=12) of mature beagles were dissected and assessed as intact, after discectomy (Dx), with implanted TE-IVD (IVD-), and with implanted TE-IVD plus BSS (IVD+) (Figure 2A-C). Using a mechanical testing frame (Figure 2D), unconfined stress relaxation tests were performed. Equilibrium and instantaneous moduli were calculated and normalized to intact motion segments. One-way ANOVA and Tukey HSD were used for statistical analysis, with p<=0.05 considered significant.
Results: Intact motion segments showed equilibrium and instantaneous moduli of 174 ± 36 kPa and 1760 ± 430 kPa, respectively, with mechanical properties from all other groups significantly lower. After normalizing to their corresponding intact motion segment mechanics, the IVD- group demonstrated relatively similar biomechanical properties to the Dx group, suggesting partial displacement and that low magnitudes of loads are shared by the construct. However, the IVD+ group demonstrated a 2-fold increase in equilibrium and instantaneous moduli (p<0.05) over the IVD- group (Figure 3A-B), with no implant displacement observed.
Conclusions: The biomechanical properties of motion segments with BSS increases the stability of TE-IVD constructs and mitigates implant displacement in canine cervical spines ex vivo, providing the impetus for future in vivo studies.
Patient Care: Degenerative disc disease (DDD) is among the most common causes of neck and back pain in the adult population. Both conservative and surgical treatment options for DDD provide symptomatic relief, but do not treat the underlying pathophysiology. Furthermore, surgical interventions including discectomy, fusion, and mechanical total disc replacement can lead to complications including reherniation, adjacent segment disease, pseudarthrosis, and hardware migration requiring additional interventions. To this end, biological approaches for IVD repair and regeneration have become of increasing interest. While a recent report has described the feasibility of transplanting whole cervical motion segments from deceased donors, tissue availability and disease transmission remains a major concern. Therefore tissue-engineered intervertebral discs serve to circumvent these limitations and may potentially provide an alternative option for patients meeting surgical intervention criteria with DDD.
Learning Objectives: By the conclusion of this session, participants should be able to 1) Describe how tissue-engineered intervertebral discs (TE-IVD) are produced, 2) Discuss, in small groups, the primary biomechanical properties used to evaluate TE-IVDs compared to native IVD and how they are tested, and 3) Understand how and why canine spine models are being used for pre-clinical testing of TE-IVDs prior to eventual human trials.
References: 1) Moriguchi Y, Santiago JM, Grunert P, et al. Total disc replacement using tissue-engineered intervertebral discs in a canine cervical spine model. In revision, Sci Tranl Med.
2) Grunert P, Gebhard HH, Bowles RD, et al. Tissue-engineered intervertebral discs: MRI results and histology in the rodent spine. J Neurosurg Spine. 2014;20(4):443-451.