Microphysiological Systems (MPS) for Precision Medicine
Authors: Monty Montano, Venkataramana Sidhaye, Martin Trapecar, Deok‐Ho Kim
Journal: Advanced Healthcare Materials (2024)

Microphysiological Systems (MPS) represent an intriguing stepping stone in efforts to replicate human biology. The premise of MPS is clear—cells, tissues, and organoids are grown ex vivo in a physiologically and anatomically accurate manner. These systems can be used as human surrogates to model disease, test drugs, and explore many other aspects of homeostasis and biology. This joint special issue aimed to curate a wide-ranging collection of works including tissue engineering, biomaterials, biofabrication, and the implementation of these advances into complex models of human pathophysiology. The issue, guest edited by Martin Trapecar, Ramana Sidhaye, and Deok-Ho Kim (founding members of the new Center for Microphysiological Systems at Johns Hopkins University), is being jointly published in Advanced Biology and Advanced Healthcare Materials. You find all articles in a virtual collection. Part I: Advanced Biology manuscripts The studies and reviews in Advanced Biology highlight significant advancements in bioengineering, specifically in the development and application of microphysiological systems (MPS), hydrogel optimization, and stem cell-derived models for biomedical research. Collectively, these efforts underscore the potential of these technologies to transform various fields, including angiogenesis, cancer immunotherapy, diabetes treatment, drug development, respiratory health, and neurological research. Lam et al. (article 202300094) developed and validated a high-throughput bioassay to assess the angiogenic bioactivity of mesenchymal stromal cells (MSCs). They identified hepatocyte growth factor (HGF) gene expression as a potential biomarker for MSC angiogenic activity. The novelty here lies in the C-Curio MPS as a tool for evaluating MSC potency and the identification of HGF as a surrogate marker. Peng and Lee (article 202300077) then review the use of MPS (e.g., organs-on-a-chip) in cancer immunotherapy research, emphasizing their advantages over traditional methods. The article highlights the application of MPS in analyzing immune cell interactions and the tumor microenvironment, with potential use in personalized medicine and immunotherapy. Quiroz et al. (article 202300502) focused on optimizing alginate hydrogels for cell encapsulation to improve viability and function for type 1 diabetes models and found conditions that enhance the function of encapsulated cells. This advance will improve cell graft viability and function in vitro. Tomlinson et al. (article 202300131) discuss the use of MPS in drug development, emphasizing the need for standardization and regulatory acceptance. They highlight the importance of defining the context of use, characterizing materials, and developing reference test items. Guo et al. (article 202300276) describe a protocol to differentiate neurons from human iPSCs and created an opioid overdose model to study respiratory inhibition by opioids. The neurons expressed the mu-opioid receptor and responded to opioids, with naloxone reversing the effects. The novelty here is in developing a cellular model for studying opioid-induced respiratory depression, offering a platform for drug screening and mechanistic investigation. Lagowala et al. (article 202300165) utilized three microphysiological models to study the pulmonary system and interactions between epithelial and immune cells in COPD and cigarette smoke injury. The models showed that co-culture with epithelial cells is necessary for macrophage polarization and altering epithelial actin dynamics. The strength of this system is the opportunity to mimic complex lung interactions, providing a more physiologically relevant platform for studying lung diseases. Morales Pantoja et al. (article 202300198) presented a method to increase the population of astrocytes and oligodendrocytes in brain microphysiological systems (bMPS) using a chemically defined glial-enriched medium (GEM). They demonstrated that GEM enhances glial cell populations, neurite outgrowth, and cell migration without compromising neuronal differentiation. The novelty is in developing a culture medium that promotes glial cell enrichment in brain organoids, improving the functionality of bMPS for neurological disease research and drug discovery. The collective findings from these studies in Advanced Biology underscore the transformative potential of advanced bioengineering techniques in biomedical research. Each study contributes novel insights and methodologies, paving the way for more realistic and effective models in various fields, with a goal of ultimately improving health outcomes and advancing the translational medicine. Part II: Advanced Healthcare Materials manuscripts The integration of MPS, organoids, and organ-on-chip (OoC) technologies represents a revolutionary shift in biomedical research, offering unparalleled opportunities to model human physiology, disease, and drug responses more accurately than ever before. In Advanced Healthcare Materials, key findings from 18 studies were published, highlighting the novelty of these technologies across multiple domains, as detailed below. Kang et al. (article 202302502) developed a high-throughput pillar/perfusion plate platform combining 3D bioprinting and microfluidic-like features for organoid cultures, enhancing reproducibility and cost-effectiveness. This innovation addresses the need for efficient disease modeling and drug screening. Kromidas et al. (article 202302714) introduced a cervical cancer-on-chip (CCoC) platform, that comprises of a PDMS-free microfluidic system integrating patient-specific cells to study the tumor microenvironment and drug responses, highlighting the importance of personalized cancer modeling. Liu et al. (article 202302686) provided a comprehensive overview of integrating microfluidic technologies with organoids, allowing precise control over microenvironments, which is crucial for organ development, disease modeling, and regenerative medicine. Urciolo et al. (article 202400357) explored the challenges in replicating functional barrier organs' microenvironments, emphasizing the dynamic role of the extracellular matrix (ECM) and the need for MPS that faithfully reproduce native cell-ECM interactions. Shoji et al. (article 202301067) conducted a literature analysis of organoid and organ-on-a-chip research, revealing significant growth in gastrointestinal and neural organoid studies and the increasing use of human cells. This work underscores the need for more detailed disease-specific models and the potential for multiorgan systems. Kim and Sung (article 202302777) reviewed advances in gut-on-a-chip systems, emphasizing the importance of incorporating physiological components such as immune cells and gut microbiota to improve model relevance. Tian et al. (article 202302104) developed an endocrine pancreas-on-a-chip using hollow microfibers for pancreatic islet cells, offering new applications in endocrine research and food safety evaluation. Wang et al. (article 202302217) provided an extensive review of liver MPS, highlighting the various design structures and cell types used, and their applications in drug development, disease modeling, and personalized medicine. Ahmad et al. (article 202304338) created an µSiM-MVM device to study leukocyte trafficking in sepsis, offering insights into endothelial cell dynamics and immune responses. Bannerman et al. (article 202302642) included epicardial cells in a heart-on-a-chip model, demonstrating improved cardiac tissue function and resilience, essential for studying cardiac development and disease. Brooks et al. (article 202302436) highlighted the use of microfluidic models to study cancer invasion and migration, providing valuable insights into metastatic mechanisms. Khorsani et al. (article 202302331) discussed the use of patient-derived organoids (PDOs) in cancer research, showcasing their potential for drug screening and understanding tumor invasion, and emphasizing the importance of personalized therapeutic strategies. Kim et al. (article 202303041) highlighted the use of iPSCs and MPS in Parkinson's disease research, demonstrating the ability to replicate disease phenotypes and study underlying mechanisms in a controlled environment. Nam et al. (article 202302682) describe an arterial model using an MPS that may inform future advances in cardiovascular disease and drug development. Smirnova and Hartung (article 202302745) reviewed brain organoids, introducing the concept of Organoid Intelligence (OI) by combining organoids with artificial intelligence to generate learning and memory capabilities, pushing the boundaries of neuroscience research. Streutker et al. (article 202303991) provided a comprehensive review of fibrosis-on-chip models, emphasizing the need for advanced models to study fibrogenesis and fibrotic diseases. Zhao et al. (article 202303419) discussed tissue-engineered microvessels, highlighting recent engineering strategies and applications, and identifying future research directions in tissue engineering. Zivko et al. (article 202302499) discusses the use of mass spectrometry imaging on organoid biology to inform preclinical studies. Finally, Mulay et al. (article 202303180) describe approaches for the development of microphysiologic blood-brain barrier systems for disease modeling and drug development, especially neurological and brain-organ crosstalk conditions. Concluding comments Collectively, the advancements in MPS, organoids, and organ-on-a-chip technologies highlighted in this joint special issue with Advanced Biology and Advanced Healthcare Materials hold transformative potential across various fields of biomedical research. These innovations offer more accurate, reproducible, and scalable models for studying human physiology, disease mechanisms, and drug responses. However, realizing their full potential requires addressing the existing challenges through ongoing research and interdisciplinary collaboration. By doing so, the scientific community can unlock new frontiers in medicine, ultimately leading to improved health outcomes and advancements in healthcare.