In vitro models of tumor vessels and matrix: Engineering approaches to investigate transport limitations and drug delivery in cancer |
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| Institution: | 1. Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA;2. Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, NY 14853, USA;1. Department of Biomedical Engineering, Micro and Nano Integrated Biosystem (MINIBio) Laboratory, USA;2. Penn State Material Research Institute, The Pennsylvania State University, University Park, USA;3. Department of Pathology, Suzhou Municipal Hospital, Affiliate Hospital of Nanjing Medical University, Suzhou, Jiangsu, China;4. Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China;5. PerMed Biomedicine Institute, Shanghai, China;6. Penn State Cancer Institute, University Park, USA;7. Department of Electrical Engineering, The Pennsylvania State University, University Park, USA;2. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA;3. Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA;4. College of Graduate Studies, Medical University of South Carolina, Charleston, SC, USA;5. Department of Surgery, Division of Cardiothoracic Research, Medical University of South Carolina, Charleston, SC, USA |
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| Abstract: | Tumor–stroma interactions have emerged as critical determinants of drug efficacy. However, the underlying biological and physicochemical mechanisms by which the microenvironment regulates therapeutic response remain unclear, due in part to a lack of physiologically relevant in vitro platforms to accurately interrogate tissue-level phenomena. Tissue-engineered tumor models are beginning to address this shortcoming. By allowing selective incorporation of microenvironmental complexity, these platforms afford unique access to tumor-associated signaling and transport dynamics. This review will focus on engineering approaches to study drug delivery as a function of tumor-associated changes of the vasculature and extracellular matrix (ECM). First, we review current biological understanding of these components and discuss their impact on transport processes. Then, we evaluate existing microfluidic, tissue engineering, and materials science strategies to recapitulate vascular and ECM characteristics of tumors, and finish by outlining challenges and future directions of the field that may ultimately improve anti-cancer therapies. |
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