Page 114 - OR-1-3

and immune cells associated with BMME niches may also advantages, such as physiological correlation, high-
have potential effects on the regulation of tumor dormancy, throughput drug screening, and real-time monitoring
as they participate in tumor dormancy and invasion. and imaging. However, their application also has several
105
For example, immune niches are also involved in tumor problems, such as data collection, integration, and analysis.
metastasis. The presence of relevant macrophage subsets A variety of manufacturing methods, such as 3D printing,
in the primary tumor is associated with the dormancy machining, injection molding, and imaging processes, can
106
or dissemination of DTCs. Therefore, future BMOC be used to fabricate an integrated and accessible platform
designs must prioritize the integration of critical immune designed for visualization and sampling. 108
components to build functional immune niches capable of
interrogating their specific roles in regulating dormancy. The rapid development of big data and artificial
Furthermore, to model the systemic aspects of metastasis intelligence technology provides new perspectives for
and dormancy (e.g., dissemination from primary sites, research on bone-related pathophysiology, and deep
homing to bone marrow, and awakening in distant information mining methods can be used to understand
organs), the development and integration of multi-organ bone structure and function. Artificial intelligence-assisted
chip platforms linking BMOCs with other relevant organ manufacturing technology can be used to optimize the
modules (e.g., liver and lung) hold immense potential but manufacturing process of bone marrow organ chips and
present substantial engineering challenges. In the future, improve their performance, including accuracy, resolution,
107
researchers need to include more metastasis-related niches and cell viability. With continuous technological
in the design of BMOCs. advancements, more detailed tumor sample data, including
information on the genome, transcriptome, proteome, and
The BMME is a highly dynamic system, and researchers
find it challenging to simulate processes, such as metabolome, can be obtained. Comprehensive analysis of
multi-omics data using methods such as machine learning
incomplete simulation of blood circulation, cell migration, and artificial intelligence can be performed to identify new
and cross-organ communication, using current organ biomarkers and predict the potential and prognosis of
chip technology. However, incorporating these factors is
necessary to elucidate mechanisms underlying diseases, tumor dormancy. To summarize, integrating microfluidic
predict pharmacokinetic parameters of drugs, and assess systems with these emerging technologies can provide new
drug pharmacokinetics. Significant bottlenecks in BMOC and effective ways to develop advanced BMOC platforms,
development and adoption persist. These include achieving facilitating further research on tumor dormancy.
standardized vascularization (e.g., size, maturity, and 6. Conclusion
perfusion stability across models), faithfully replicating
complex inter-niche signaling (e.g., soluble factors, The BMME plays a pivotal role in tumor dormancy,
direct cell contact, and ECM cues), and ensuring high with significant implications for cancer metastasis and
reproducibility both within and between laboratories. recurrence. The innovative BMOC technology has
emerged as a valuable tool for modeling and investigating
Researchers have proposed a flexible approach, which
is similar to modular platforms like Tetris, for integrated the complex interactions within the BMME, offering novel
human chip systems. The platform offers the flexibility insights into the regulatory mechanisms of tumor cell
to be constructed and deconstructed according to dormancy. Despite the current limitations in replicating
analytical requirements. It enhances user convenience in the full complexity of the BMME using BMOCs, ongoing
pharmacological studies and mitigates leakage hazards. advancements promise to refine the understanding of tumor
Nonetheless, ongoing challenges include restricted dormancy. Future research should focus on enhancing
processing capacity, inter-module communication the physiological fidelity of BMOCs and leveraging this
complexities, and issues with compatibility. 108,109 To technology to develop more effective therapeutic strategies
overcome these limitations, the integration of cutting-edge for managing cancer dormancy and preventing relapse.
tools is paramount. Artificial intelligence can accelerate
design optimization, predict cellular responses, and Acknowledgments
analyze complex multimodal data streams generated by None.
chips. Incorporating PDOs or other patient-specific cells
into BMOCs offers a powerful path towards personalized Funding
medicine applications and better modeling of human- We are grateful for the support from the Guangdong
specific dormancy mechanisms. Basic and Applied Basic Research Foundation
In contrast to conventional cell culture platforms (2023A1515011544) and the National Science Foundation
and animal-based models, BMOC systems have many of China (32101097).

Volume 1 Issue 3 (2025) 17 doi: 10.36922/OR025200017