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

Abstract

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 crosscellular 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 β-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.

Exploring Bone Cell Research Using Bone-on-a-Chip Models and Microfluidics: A Literature Review

“…Alternatively, one of the materials suggested to make ceramic scaffolds is β-tricalcium-phosphate (β-TCP) due to their ability to fabricate porous scaffolds allowing for the development of a dense ECM that is required for bone remodelling [10]. Erbay et al (2023) proposed a 3dimensional bone co-culture where primary osteoblast and F4/F80 + osteoclast precursors were seeded in the TCP base scaffold and cultured in a microfluidic setup for up to 21 days. A polymer foam replication method was used to make the scaffold and the TCP powder was grinded down to control the geometry of the scaffold.…”

“…A polymer foam replication method was used to make the scaffold and the TCP powder was grinded down to control the geometry of the scaffold. X-ray diffraction (XRD) analysis was able to show that the scaffold was able to retain osteogenic properties and SEM was able to show that macropore sizes ranged from 500 to 50 μm, while micropore sizes ranged from 10 to 1 μm indicating that the scaffold is very porous [15]. Computational fluid dynamic simulations were able characterize the flow pattern in the bone-on-a-chip model which showed that the flow velocity was slower near the boundaries of the channels than in the corner [15].…”

“…Computational fluid dynamic simulations were able characterize the flow pattern in the bone-on-a-chip model which showed that the flow velocity was slower near the boundaries of the channels than in the corner [15]. Bone marrow mesenchymal stem cells (BMMSCs) and osteoclast precursors were cocultured [15]. After 21 days, SEM analysis was used to discover that a substantial amount of ECM was produced within the scaffold [15].…”

“…Bone marrow mesenchymal stem cells (BMMSCs) and osteoclast precursors were cocultured [15]. After 21 days, SEM analysis was used to discover that a substantial amount of ECM was produced within the scaffold [15]. There was also a greater amount of cellular attachment and cell proliferation [15].…”

“…After 21 days, SEM analysis was used to discover that a substantial amount of ECM was produced within the scaffold [15]. There was also a greater amount of cellular attachment and cell proliferation [15]. Tissue scaffolds were then placed in mice for 8 weeks which revealed the platform had high osteoinductivity [15].…”