Spinal fusion surgery is often the answer to cases of severe intervertebral disc degeneration where the cushioning that sits between the spinal vertebrae becomes damaged, causing patients to experience back and neck pain. However, the surgery does not restore native structure or mechanical function. Degeneration of the intervertebral disc (IVD) is due to combination of cellular, compositional and structural changes including a loss of proteoglycan in the nucleus pulposus (NP), the inner core of the disc; disruption of the annulus fibrosus; the exterior portion of the disc; and a collapse in disc height. The basis of spinal fusion surgery is to remove the degenerated disc, replace with a bone graft, and fastened screws to adjacent vertebrae to “fuse” the replacement bone. The spinal fusion can cause a loss of flexibility and an increased chance in similar discs becoming compromised as a result of compensating for the removed disc.
Advancements in tissue engineering has led to scientists from the University of Pennsylvania to develop endplate-modified disc-like angle ply structures or eDAPS for short, as a solution to spinal fusion surgery that reduces pain but also restores native function and motion.
The eDAPs are composed of three layers with two cell-seeded layers to replace the AF and NP region, and an acellular porous foam as endplate analogs. Scientists used concentric layers of aligned, nanofibrous poly(ε-caprolactone) (PCL) for the AF region as it is easily produced through electrospinning, has strong mechanical properties, and has a slow rate of degradation. For the NP region, a hyaluronic acid or agarose hydrogel was used to mimic the natural hydrated state of native NPs. The two regions were seeded with cultured bovine disc cells and constructed together with two acellular, porous PCL foams as endplate analogs.
The replacement discs were first tested in rats. Scientists were able to successfully demonstrate the restoration or maintenance of the mechanical properties of the rat tail as well as in vivo integration and maturation of the engineered disc. The eDAPS were then scaled up to adapt into large animal models to demonstrate possible integration in humans. A goat model was chosen and allogenic goat bone marrow-derived MSCs were used to seed the construct as relevant model for future implementation. The eDAPS were transplanted into the spine of the goat model with an MRI providing data on the progression of the construct. The goat eDAPS demonstrated that mechanical properties were maintained with in vivo integration and maturation that were comparable to native IVDs.
Scientists did encounter a few limitations such as slower growth of cells for the larger construct and the necessity of external and internal fixation to stabilize the eDAPS construct. Although there a considerable way to go before work is conducted in humans, the study is promising for the implementation of engineered tissue for the treatment of spinal damage.
This article titled “Long-term mechanical function and integration of an implanted tissue-engineered intervertebral disc” was published in Science Translational Medicine.