Bioprinted Bonoid-on-a-Chip Model Reveals Dexamethasone Disrupts Human Osteocyte Mechanosensing
Background
Studying bone homeostasis and diseases like osteoporosis and osteoarthritis is challenging due to the lack of physiologically relevant human in vitro models. Osteocytes, embedded within bone, form a dendritic network crucial for sensing mechanical and biochemical stimuli, a process known as mechanotransduction. Current models often fail to replicate the complex interplay of perfusion, mechanical loading, and oxygen tension, hindering our understanding of osteocyte differentiation and drug effects. This gap necessitates advanced microphysiological systems to better mimic the native bone microenvironment.
Study Design
Researchers developed a Bonoid-on-a-chip (BoC) platform by bioprinting primary human osteoblasts into a gelatine-hydrogel. These bonoids were cultured under either static conditions or as dynamic BoC. The dynamic BoC environments included controlled perfusion (0.5 ml min-1), mechanical loading (0% or 10% compression, 1 Hz frequency), and physiological oxygen tension (21% or 12%) over a seven-day period. To evaluate drug effects on early osteocyte differentiation, models were additionally treated with dexamethasone (DEXA). Cell viability, metabolic activity, morphological changes, and mechanotransduction markers were assessed using various assays.
Results
High cell viability was maintained across all conditions, but significant differences in metabolic activity, morphological changes, and mechanotransduction markers were observed between static and dynamic cultures. Cells within the BoC-platform exhibited extended dendritic processes, a key characteristic of osteocytes. More importantly, mechanical stimulation in the dynamic BoC led to significantly increased secretion of prostaglandin E2 and nitrite, which are established hallmarks of osteocytic signaling in mechanotransduction. This demonstrates the model's ability to accurately replicate crucial osteocyte functions. > When testing the BoC platform for early osteocyte-targeted investigations, dexamethasone exposure was found to disrupt this mechanoresponsive phenotype, indicating a direct impact on osteocyte function and highlighting the model's utility for drug screening.
Key Findings
- Bioprinted bonoid-on-a-chip (BoC) model successfully cultured human osteoblasts in a 3D gelatine-hydrogel.
- Dynamic BoC cultures showed clear differences in metabolic activity and morphology compared to static conditions.
- BoC cells developed extended dendritic processes, characteristic of mature osteocytes.
- Mechanical stimulation in BoC significantly increased
prostaglandin E2andnitritesecretion, indicating robust mechanotransduction. - Dexamethasone exposure disrupted the mechanoresponsive phenotype in the BoC model.
Why It Matters
This bioprinted Bonoid-on-a-chip model represents a significant advancement for studying bone diseases and screening potential therapeutics. By accurately mimicking the complex mechanical and biochemical environment of human bone, it offers a more physiologically relevant platform than traditional 2D cultures. The BoC model enables targeted drug screening for bone diseases by mimicking human osteocyte mechanotransduction in vitro, potentially accelerating the discovery of compounds that preserve or restore bone health. This could lead to more effective treatments for conditions like osteoporosis by identifying drugs that specifically modulate osteocyte function and mechanosensing, moving beyond current systemic approaches.
bone-homeostasis
osteoporosis
osteoarthritis
mechanotransduction
osteocyte-differentiation
bioprinting