Research Areas

CANCER CELL-MATRIX INTERACTIONS

The tumor microenvironment is a complex milieu of cancer cells, fibroblasts, endothelial cells, immune cells and other supporting cell types. In addition, the dysregulated extracellular matrix (ECM) components further support the complex interactions driving tumor growth and invasion. Establishing 3D in vitro models of the tumor microenvironment can be helpful in elucidating and decoupling these interactions as well as investigate the mechanistic role of the tumor ECM in driving tumorigenesis and metastasis. We employ biomimetic hydrogels based on poly(ethylene glycol diacrylate) coupled with proteins or specific peptide sequences that can be tuned with respect to stiffness, adhesivity, degradability and other biophysical characteristics. Using these hydrogels, we aim to investigate 3D cancer cell behavior in the engineered microenvironments and subsequently increase model complexity and physiological relevance via co-culture with other cell types. This approach allows us to investigate specific aspects of tumor progression: tumorigenesis, invasion, zonal heterogeneity, tumor dormancy, and recurrence.

Publications

  • S Pradhan, JH Slater. Tunable Hydrogels for Controlling Phenotypic Cancer Cell States to Model Breast Cancer Dormancy and Reactivation. Biomaterials 2019, 215:119177. DOI: https://doi.org/10.1016/j.biomaterials.2019.04.022

  • S Pradhan, JH Slater. Fabrication, Characterization, and Implementation of Engineered Hydrogels for Controlling Breast Cancer Cell Phenotype and Dormancy. MethodsX 2019, 6:2744. DOI: https://doi.org/10.1016/j.mex.2019.11.011

  • S Pradhan, JH Slater. Datasets Describing Hydrogel Properties and Cellular Metrics for Modeling of Tumor Dormancy. Data in Brief 2019, 25: 104128. DOI: https://doi.org/10.1016/j.dib.2019.104128

  • S Pradhan, I Hassani, WJ Seeto, EA Lipke. PEG-fibrinogen Hydrogels for Three‑dimensional Breast Cancer Cell Culture. Journal of Biomedical Materials Research Part A 2017, 105(1): 236-252. DOI: https://doi.org/10.1002/jbm.a.35899

MICROPHYSIOLOGICAL PLATFORMS

The ability to recapitulate the complex tumor microenvironment has been greatly facilitated by the development of microfluidic-based on-chip platforms. These devices incorporate hydrogel matrix based 3D cultured tumor cells in co-culture with fibroblasts and well-established lumenized microvascular networks composed of tumor-associated endothelial cells. These platforms can be used to investigate dynamic tumor-vascular interactions as well as microvascular flow dependent delivery of chemotherapeutics to tumor tissues.

Publications

  • S Pradhan, A Smith, C Garson, I Hassani, WJ Seeto, K Pant, RD Arnold, B Prabhakarpandian, EA Lipke. A Microvascularized Tumor-mimetic Platform for Assessing Anti-Cancer Drug Efficacy. Scientific Reports 2018, 8:3171. DOI: https://doi.org/10.1038/s41598-018-21075-9

TISSUE NICHE FABRICATION TECHNOLOGIES

Hydrogel matrices can be fabricated with controlled shape and scale-spanning sizes by employing a variety of techniques including surface-tension based suspension, oil-in-water emulsion and droplet microfluidics. Encapsulated cells within these hydrogel constructs can be employed for investigation of tissue-specific niches, recapitulation of tumorigenic phenomena or for high-throughput drug screening. Multiple cancer cell types can be employed to form tumor microspheres or tumor millibeads that mimic native micrometastates or larger millimeter-scale tumors.

Publications

  • WJ Seeto, Y Tian, S Pradhan, P Kerscher, EA Lipke. Rapid Production of Cell Laden Microspheres Using a Flexible Microfluidic Encapsulation Platform. Small 2019, 15(47): 1902058. DOI: https://doi.org/10.1002/smll.201902058

  • S Pradhan, JM Clary, D Seliktar, EA Lipke. A Three-dimensional Spheroidal Cancer Model Based on PEG-fibrinogen Hydrogel Microspheres. Biomaterials 2017, 115:141-154. DOI: https://doi.org/10.1016/j.biomaterials.2016.10.052

  • S Pradhan, CS Chaudhury, EA Lipke. Dual-phase, Surface Tension-based Fabrication Method for Generation of Tumor Millibeads. Langmuir 2014, 30(13): 3817-3825. DOI: https://doi.org/10.1021/la500402m