Development of a chick embryo spinal cord injury model as a platform to test neural tissue engineering strategies

Abstract

Spinal cord injury is a devastating condition affecting thousands of people every year. The spinal cord does not have the intrinsic capacity for regeneration due to a complex cascade of physical and chemical barriers that prevent axonal growth and lead to neuronal death and, therefore, current treatments are yet to achieve full functional repair. The implantation of encapsulated neural stem cells within 3D matrices offers the advantages of cellular repopulation, release of neurotrophic factors and healthy extracellular matrix mimicking, leading to improved motor function. However, neural tissue engineering strategies face three main challenges: the exclusive use of experimental grade biomaterials for research, the overlooking of the highly aligned structure of the spinal cord and the reliance on complex and expensive in vivo rodent animal models, leading to time consuming experiments which make reproducibility challenging. As an alternative, we propose the use of chick embryo spinal cord organotypic slices as a novel spinal cord injury model as it offers a cheaper alternative linked to less ethical implications.
Here, we established for the first time a transecting spinal cord injury model using the chick embryo as a donor of spinal cord slices. We also tested two biomaterials for their capacity to incorporate a relevant cell transplant population: HemopatchTM, a clinically available scaffold, and CellevateTM, an aligned nanofibre biomaterial. We demonstrated the viability of both matrices for incorporating a healthy cell population, we showed improvement of cell distribution through laminin engineering on HemopatchTM and we described a protocol for measuring cellular alignment with CellevateTM. Finally, we tested the feasibility of biomaterial implantation in the spinal cord injury model described earlier, resulting in the typical cellular responses expected in an adult injury.
The model, which presents comparable responses to those based on murine models, represents a simpler alternative to previously established models. The adoption of this model could lead to impactful research while maintaining a cost effective and technically simple methodology. This could have translational potential for other research areas, such as the study of degenerative diseases, and potentially increase the research output on the study of spinal cord injury therapies which, in turn, would lead to a faster translation of functional therapies to higher complexity models and, finally, to the clinic.