283 Decoding Mechanotransduction in Spinal Pseudoarthrosis: A Mouse Model of Spinal Fusion for Developing Mechanosensitive Osteobiologics

Abstract

INTRODUCTION: Pseudoarthrosis (PA), represents a significant complication after spinal fusion. Efforts to reduce its occurrence predominantly involve the use of osteobiologics, the majority of which, are linked to various complications. It is well known that bone formation relies heavily on mechanical signaling cues. Recently, Piezo 1 has emerged as an important mechanosensitive calcium channel with a role in bone formation during development. METHODS: Normal human spine bone samples and PA tissue samples were collected intraoperatively. Samples underwent biomechanical and histologic characterization. Mice underwent spinal fusion surgery using iliac crest allograft. Weekly micro CT scans were performed over 4 weeks. Explanted mouse fusion bed (week 4) and normal spine underwent three-point bending testing. RESULTS: Human PA tissue was an elastic tissue that did not contain any mineralized bone with a mechanical stiffness of 12±4.1 N/mm. Bone had a measured stiffness of 341 ± 70 N/mm. Immunostaining showed that bone contained Piezo 1 expressing cells. PA demonstrated loss of osteocytes and loss of Piezo 1 expression. Mouse micro CT imaging of fusion bed at week 4 showed contiguous areas of fused bone. Fused mouse spine had a stiffness of 5.87 ± 2 N/mm. Normal mouse spine had a stiffness of 1.17 ± 0.47 N/mm. CONCLUSIONS: Human PA tissue is biomechanically and histologically distinct from normal bone with loss of Piezo 1 and osteocytes. Mice that underwent fusion surgery displayed radiographic and biomechanical evidence of bone fusion in a Piezo1-dependent manner, revealing a role for targeting mechanosensitive channels as a local biologic to promote arthrodesis.