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Abstract:
Hepatic osteodystrophy is a metabolic bone disease associated with chronic liver diseases. Its pathogenesis has not been clearly identified due to the difficulty in capturing inter-organ interactions through traditional models. This study constructed a dual-organ perfusion microphysiological device, integrating human liver and bone tissue scaffolds to achieve dynamic co-culture. By inducing liver fibrosis to simulate the pathological environment, the study explored the interaction between the hepatic and bone axes and drug-related responses, providing a new tool for the study of the disease mechanism.
01 Research Background
Hepatic osteodystrophy is characterized by impaired bone remodeling, reduced mineralization, and abnormal dynamics of osteoblasts and osteoclasts. It is closely related to chronic liver diseases. The study of the mechanism of the hepatic-bone axis has significant scientific value, but traditional in vitro and in vivo models have inherent limitations in reproducing organ interferences, making it difficult to precisely replicate the interactions between organs in the physiological state, which restricts in-depth analysis of the disease.
02 Main Content
This study focuses on the exploration of the pathological mechanism of the hepatic-bone axis, developing a dual-organ perfusion microphysiological device that integrates human liver and bone tissue scaffolds to achieve dynamic co-culture. Through one-way perfusion, a dynamic co-culture system was constructed; using chemical substances to induce liver fibrosis to simulate the pathological state, the study observed the impact of the hepatic-bone axis interaction on bone homeostasis; at the same time, model drugs were introduced to verify the application potential of the device in related mechanism studies.
03 Research Design
A single-directional perfusion dual-organ microphysiological device was built, embedding human liver and bone tissue scaffolds to achieve dynamic co-culture of hepatocyte spheres and osteogenesis, ensuring the dynamic exchange of metabolites, cytokines, and signaling factors; the chemical induction method was used to construct a pathological model of liver fibrosis, comparing the pathological simulation effects of static culture and dynamic perfusion systems; model drugs were introduced to observe their effects on the hepatic-bone axis and bone homeostasis in the dynamic system.
04 Results
The pathological environment of liver fibrosis triggers changes in inflammatory cytokines, which interfere with bone homeostasis, leading to enhanced activation of osteoclasts, reduced function of osteoblasts, and decreased mineral deposition. This successfully reproduces the characteristic features of hepatic osteodystrophy; compared with static culture, the dual-organ perfusion device can more accurately replicate the pathological interactions between the liver and bone; the effects of model drugs and their metabolites on bone homeostasis in the device are consistent with physiological results.
05 Extension of Thoughts
The device can be further optimized in terms of tissue compatibility and dynamic regulation performance to deeply analyze the cytokine network and signal regulation mechanisms related to the hepatic-bone axis; the device can be expanded to different types of chronic liver disease-related bone diseases, providing more comprehensive technical support for the study of disease pathogenesis; exploring the pathological simulation ability of the device under the regulation of multiple factors can improve the related research technical system.
Original Source:
1. Journal: ACS Nano
2. Publication Date: December 18, 2025
3. DOI: 10.1016/j.bioactmat.2025.12.01 4. Authors: Purva Gupta, Shreya Mehrotra, Romina H. Aspera-Werz, Ayushi Mairal, Ashiq Hussain Pandit, Andreas K. Nüssler, Ashok Kumar
