Challenges to bone formation in spinal fusion.

Spinal arthrodesis continues to expand in clinical indications and surgical practice. Despite a century of study, failure of bone formation or pseudarthrosis can occur in individual patients with debilitating clinical symptoms. Here we review biological and technical aspects of spinal fusion under active investigation, describe relevant biomechanics in health and disease, and identify the possibilities and limitations of translational animal models. The purpose of this article is to foster collaborative efforts with researchers who model bone hierarchy. The induction of heterotopic osteosynthesis requires a complex balance of biologic factors and operative technique to achieve successful fusion. Anatomical considerations of each spinal region including blood supply, osteology, and biomechanics predispose a fusion site to robust or insufficient bone formation. Careful preparation of the fusion site and appropriate selection of graft materials remains critical but is sometimes guided by conflicting evidence from the long-bone literature. Modern techniques of graft site preparation and instrumentation have evolved for every segment of the vertebral column. Despite validated biomechanical studies of modern instrumentation, a correlation with superior clinical outcomes is difficult to demonstrate. In many cases, adjuvant biologic therapies with allograft and synthetic cages have been used successfully to reproduce the enhancement of fusion rates observed with cancellous and tricortical autograft. Current areas of investigation comprise materials science, stem cell therapies, recombinant growth factors, scaffolds and biologic delivery systems, and minimally invasive surgical techniques to optimize the biologic response to intervention. Diverse animal models are required to approach the breadth of spinal pathology and novel therapeutics.