BACKGROUND: On-site delivery of bioactive agents facilitates enhancing the effectiveness of spinal fusion. However, the FDA-approved agents currently used in clinical practice are limited by side effects and cost issues, urging exploration of new alternatives.

AIM: This study aimed to investigate the effectiveness of KMN-159, a novel selective prostaglandin EP4 receptor agonist with osteopromotive properties, in spinal posterolateral fusion (PLF) surgery.

METHODS: Various doses of KMN-159 were delivered locally using a mineralized collagen matrix (MCM) scaffold, and its efficacy results were compared with FDA-approved recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat lumbar PLF model. 192 male Wistar rats, aged 10 weeks, were randomized into 8 groups: 1) SHAM, 2) MCM, 3) MCM +10 μg rhBMP-2 (per scaffold), 4-8) MCM + 0.1, 1, 10, 100 or 1000 μg KMN-159 (per scaffold). PLF surgery was performed at the L4-5 level, and animals were euthanized after 3 and 6 weeks for spinal fusion evaluation.

RESULTS: KMN-159 exhibited dose-dependent osteopromotive effects on osteoblasts, osteoclasts, and vascular ingrowth within MCM carriers, resulting in new bone formation in a dose-dependent manner. The mid- and high-dose KMN-159 (10, 100, and 1000 μg) groups significantly enhanced PLF with biomechanical improvement, while low-dose (0.1 and 1 μg) groups were insufficient to achieve lumbar fusion.

CONCLUSION: KMN-159 emerges as a novel osteopromotive factor, coupled with its functionalized MCM scaffold presents a potential bioactive material for enhancing PLF surgery outcomes.