Oregon Health & Science University (OHSU) has secured over $9 million in funding from the National Institutes of Health (NIH) to spearhead pioneering research developing microphysiologic systems, widely recognized as organs-on-a-chip, which replicate the intricacies of cancer growth, metastasis, and therapeutic responses specifically within bone and related tissues. These cutting-edge engineered human tissue platforms are poised to revolutionize our comprehension of bone-associated cancers, an area hitherto plagued by a lack of effective models and significant clinical challenges.
The latest funding complements a landmark $3.5 million NIH grant awarded in 2025 to Luiz Bertassoni, D.D.S., Ph.D., director of the Knight Cancer Precision Biofabrication Hub at OHSU, bringing the total NIH commitment to nearly $9.2 million. These grants, led by Bertassoni and Alexander Davies, D.V.M., Ph.D., represent a strategic thrust by OHSU’s Knight Cancer Institute to meld bioengineering, oncology, and precision medicine. This initiative underscores the transformative potential of sophisticated tissue engineering to elucidate the complex microenvironments encountered by cancers invading bone, facilitating research that had previously been unattainable.
At the heart of this research are microphysiologic systems, diminutive yet intricate devices roughly the size of USB drives, composed of living human cells organized in three-dimensional arrays to faithfully recapitulate tissue architecture and function. These chip-based models integrate multiple cell types, including bone osteoblasts, endothelial cells constituting blood vessels, and neural components, enabling dynamic, real-time observation of cancer cell behavior, signaling interactions, and responses to therapeutics at unparalleled single-cell resolution. This biofabrication approach addresses a critical shortfall in conventional cancer models, which often fail due to oversimplification or species differences inherent in animal studies.
Alexander Davies leads a $3.17 million project focusing on osteosarcoma, a highly aggressive and rare pediatric bone cancer with a stagnant survival rate, especially in patients with pulmonary metastases. By engineering bone and ex vivo lung microenvironments within these microfluidic chips, Davies’ team enables visualization and monitoring of metastatic tumor cells as they colonize lung niches and interact with the surrounding microenvironment. This allows researchers to dissect metastatic processes and evaluate drug responses in a controlled yet physiologically relevant setting, a significant leap beyond static cultures or animal models.
A particularly promising avenue investigated within these osteosarcoma models targets MCL-1, an anti-apoptotic protein that aids cancer cell survival in the metastatic lung microenvironment. Previous collaborative studies utilizing animal and lab models demonstrated that MCL-1 inhibitors, especially when combined with cyclophosphamide chemotherapy, substantially impair metastatic tumor viability and sometimes eradicate lung tumors entirely. However, the precise action mechanism, specificity, and safety profiles remain to be fully elucidated in human-relevant models, which Davies’ cutting-edge organ chips provide.
Meanwhile, Bertassoni’s $2.5 million NIH award aims to unravel the biomechanical and neurovascular determinants that govern prostate cancer metastasis to bone, a phenomenon clinically observed in over 80% of men with advanced prostate cancer. His lab’s bone-on-a-chip systems incorporate live blood vessels and nerve cells within engineered human bone tissue, creating an unprecedented platform to investigate how mechanical forces—such as shear stress and vessel wall compression—and neural signaling synergistically facilitate tumor cell extravasation, survival, and aggressive growth within the bone niche.
The integration of vasculature and neural elements into a single microphysiologic device represents a significant bioengineering accomplishment. This holistic platform enables detailed mechanistic studies on how physical and biochemical cues influence gene expression patterns in metastatic cancer cells and their crosstalk with the resident bone microenvironment. Bertassoni emphasizes the active role of bone as a dynamic tissue whose hemodynamic and neural features critically shape cancer progression, challenging the traditional view of bone as a passive metastatic site.
Beyond prostate cancer, this organ-on-chip technology demonstrates adaptability to various cancer types, including head and neck cancers that aggressively invade bone tissue, as reflected by prior NIH funding to Bertassoni’s lab. The modularity of these platforms facilitates exploration of diverse tumor-stroma interactions, drug screening, and personalized medicine applications, positioning OHSU at the forefront of biofabrication-driven cancer research.
These NIH awards epitomize an intentional interdisciplinary ecosystem cultivated at OHSU, where bioengineers, cancer biologists, clinicians, and imaging specialists collaborate synergistically within the Knight Cancer Institute’s Precision Biofabrication Hub. This collaborative framework accelerates innovation and amplifies the translational impact of research, with the ultimate aim of improving clinical outcomes for patients afflicted by challenging bone-metastatic cancers.
In summary, the integration of advanced biofabrication, microfluidics, and cellular engineering embodied in these NIH-funded projects heralds a new era in oncology research. By recreating physiologically relevant human tissues on microchips, scientists can probe cancer metastasis mechanisms with unprecedented clarity, evaluate therapeutic interventions more effectively, and pave the way towards novel, targeted treatments tailored for bone-invading malignancies.
Envisioning the profound implications, Bertassoni notes, “Our biofabrication models enable an in-depth exploration of cancer complexity and therapeutic vulnerabilities that were inaccessible before. These efforts mark a pivotal step in translating engineered human tissue technologies into meaningful clinical insights.”
Davies concurs, emphasizing the translational promise: “Our osteosarcoma models resolve long-standing challenges in studying metastatic progression and therapy resistance. They hold great potential to transform patient care by enabling safer, more effective treatment strategies grounded in robust, human-relevant science.”
Collectively, these projects underscore the NIH’s strategic shift towards promoting human-relevant experimental platforms and signal a transformative advance in understanding, treating, and ultimately overcoming bone metastatic cancers.
Subject of Research: Development and application of microphysiologic systems (organs-on-a-chip) to study cancer growth, metastasis, and therapeutic response in bone and bone-associated tissues.
Article Title: Revolutionizing Bone Cancer Research: Engineering Human Tissues on a Chip to Decode Metastasis and Treatment Response
News Publication Date: Not specified in the source content.
Web References:
- Knight Cancer Precision Biofabrication Hub: https://www.ohsu.edu/knight-cancer-institute/precision-biofabrication-hub
- NIH Funding Announcement for Bertassoni: https://news.ohsu.edu/2025/07/28/ohsu-research-team-lands-federal-funding-to-study-aggressive-head-and-neck-cancer
- Osteosarcoma Lung Metastasis Research Publication: https://pubmed.ncbi.nlm.nih.gov/37676378/
- Prostate Cancer Bone Metastasis Statistics: https://www.sciencedirect.com/science/article/pii/S0046817700800350?via%3Dihub
References: Relevant NIH grant numbers: R01CA300732-01A1 (Davies), R01CA310177 and R01DE035326 (Bertassoni).
Image Credits: OHSU/Christine Torres Hicks
Keywords: Bone cancer, osteosarcoma, prostate cancer metastasis, organs-on-a-chip, microphysiologic systems, biofabrication, tissue engineering, biomedical engineering, cancer metastasis, microfluidics, MCL-1 protein, cancer therapeutic development
