Rat Spine Fusion Models for Preclinical Research: Opportunities and Challenges

Rodent models have gained popularity for assessing the efficacy and safety of experimental spine fusion methods in preclinical research, but variability in surgical technique, graft materials, and outcome assessment has limited standardization across studies. This review highlights key developments in rat spinal fusion models, focusing on the strengths and limitations of the surgical techniques applied and advancements in quantitative and qualitative outcome measures, aiming to identify opportunities for increased consistency in experimental designs. A comprehensive literature review was performed by using PubMed to include studies utilizing rat models for spinal fusion. Posterolateral intertransverse fusion remains the most widely used model, often employing autografts or biologically enhanced scaffolds as controls, while the Wiltse paraspinal approach is chosen when minimal invasiveness is favored. Functional fusion outcome assessments have evolved from manual palpation and traditional radiography to sophisticated microcomputed tomography (μCT) analyses along with histological scoring and serum marker analyses. Consensus biomechanical analyses of rodent spine fusion outcomes remain lacking. Emerging rodent data on the effects of pharmacologic agents, systemic conditions, and biologic implants on fusion show wide-ranging fusion rates from 0% to 100% across studies. Overall, this review points to the need for standardization in surgical technique, control bone grafts, and multimodal outcome assessment to enhance the rigor, reproducibility, and translational relevance of rat spine fusion models for the early stage research and development of novel therapeutic interventions.