PROJECT SUMMARY There is an unmet need for understanding the complex relationships between the compliance of interbody fusion cages, interbody loading, load-sharing, and the progression of spinal fusion in vivo. Interbody fusion cages are spinal implants that have become highly popular over the last decade. An ideal interbody fusion cage should be sufficiently stiff and strong to limit interbody motion and relieve the pressure that may be causing pain, while “compliant” enough to allow sufficient load to be transferred through the spine to maintain bone. We propose to investigate the effect of the mechanical compliance of interbody cages on the spinal fusion rate and the subsidence of spinal segments in ovine models. To this aim, we will create the first-of-their-kind compliant metamaterial fusion cages with tunable stiffness, porosity and energy absorption, and will implant them in ambulatory vertebrate animals. We hypothesize that the proposed metamaterial interbody cages with local compliance and reduced stiffness foster more consistent load-sharing during the full range of motion from flexion to extension. This is clinically significant because load-sharing through the interbody space stimulates bone formation and maturation and may ultimately lead to better outcomes. Therefore, we hypothesize that the compliant metamaterial cages introduce a softer stabilization approach leading to a faster bone formation and better fusion. Our first objective will be to perform topology optimization to develop a series of “mechanically-optimized” metamaterial cages, which can be adapted to function in animal models. We will create a computational framework that can serve as a universal method for the accelerated design of the compliant fusion cages across a full relative density range with various biocompatible material options. The fabricated cages will be mechanically tested following the protocols described by the ASTM standards F2077 and F2267 to establish their static/dyn