The Murine Caudal Pre-clinical Model for Graft-Mediated Mesenchymal Tissue Regeneration in the Spine.

Abstract

Degenerative disc disease is a major cause of spinal pathology. As the intervertebral disc is an avascular structure it has a limited capacity for self-repair. A surgical method for treating severe pathology is spinal fusion surgery. Regenerative medicine is a field of therapeutic research that aims to repair or regenerate tissues using the body’s own repair mechanisms. The regeneration of intervertebral disc tissues has the potential to significantly improve patient outcomes.

A novel, bioresorbable scaffold has been developed by our research group. This thesis investigates the application of this bio scaffold for bone and cartilage tissue regeneration within the spine. Multiple opportunities throughout this thesis have arisen for the design and fabrication of implants, surgical aids, and research aids. A rapid templating process, previously described by our research group, was validated for efficient fabrication of parts used throughout this thesis.

A clinically replicative surgical protocol of spinal fusion was used. However, implant retropulsion prevented assessment of tissue formation. Intervertebral fixation systems for the rat caudal segment were then conceptualised and fabricated. An ex vivo model was used to assess their surgical application. However, no fixation system was found to be viable for use in vivo.

Considering these outcomes, a new preclinical method was required. A novel, accessible, and standardisable drill hole defect model for spinal implant testing was designed in the rat caudal spine. Series micro-CT, high resolution X-ray, and CT imaging in conjunction with histology was conducted. The stable vertebral defect environment fostered bone integration throughout the bio scaffold. Although some intervertebral defects showed intervertebral bone bridging, the bio scaffold was seen to foster neo fibrovascular and pre-fibrovascular tissue integration. These outcomes have provided a solid basis for the progression of bio scaffold preclinical testing.