In Vitro Maturation and In Vivo Integration and Function of an Engineered Cell-Seeded Disc-like Angle Ply Structure...

Total disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ. However, DAPS rapidly lost proteoglycan post-implantation and did not integrate into adjacent vertebrae. To address this, we modified the design to include polymer endplates to interface the DAPS with adjacent vertebrae, and showed that this modification mitigated in vivo proteoglycan loss while maintaining mechanical function and promoting integration. Together, these data demonstrate that cell-seeded engineered discs can replicate many characteristics of the native disc and are a viable option for total disc arthroplasty.