Bioengineering Bone-on-a-Chip Model Harnessing Osteoblastic and Osteoclastic Resolution

Organ-on-a-chip (OoC) systems allow the generation of microphysiological tissue models that can recapitulate key biological processes in healthy and diseased states. OoC bone models provide valuable tools to study cross-cellular interactions that take place in bone-related processes. Although few bone-on-a-chip models have been proposed, structural and biological hierarchy to establish a functional unit is often lacking. Herein, a functional OoC-based 3D bone co-culture model is reported. This model comprises a highly porous beta-tricalcium phosphate (TCP) based scaffold that is seeded with primary osteoblast and osteoclast precursors. This engineered construct is formed and cultured dynamically inside an OoC platform for up to 21 days and exhibits a dense extracellular matrix (ECM). Further, cultured constructs are ectopically implanted in C57BL/6 mice for 8 weeks, then histological and tartrate-resistant acid phosphatase (TRAP) analyses are carried out. These results demonstrate that both bone deposition and resorption processes are present in the bioengineered model. This study also has implications for understanding complex cellular cross-talks occurring in the bone remodeling process.