Discipline: Technology and Engineering
Subcategory: Cancer Research
Session: 1
Room: Virginia B
Sarah Chaji - University of Georgia
Co-Author(s): Jenna Alsaleh, University of Georgia, Athens; Cheryl Gomillion, University of Georgia, Athens
With breast cancer remaining one of the leading causes of cancer death in women, there is increasing demand for the development of novel breast cancer cell/tissue models mimicking the breast microenvironment, which could be used for evaluating tumor cell behavior and screening of therapeutics. Postmenopausal women are 1.5 times more inclined to obtain breast cancer if overweight and 2 times more likely if obese.1 Currently, widely used two-dimensional (2D) models (i.e., monolayer cultures of cells) are limited due to a lack of appropriate chemical and physiological architecture of the complex breast microenvironment. Thus, three-dimensional (3D) in vitro models have been increasingly investigated for improved cell and disease modeling platforms.2 At present, 3D bioprinting has emerged as a popular method for fabricating 3D tissue structures, however, the primary obstacles with 3D bioprinting are cost and size of some printers. Existing 3D bioprinters tend to be large and cost from $10,000 to over $200,000.3 Our goal with this work is to establish the feasibility for efficiently and economically fabricating bioprinted models of the breast tumor microenvironment.
In the present study, a modified low-cost extrusion-based 3D printer was optimized to print microtissues composed of a composite alginate and gelatin hydrogel embedded with MCF-7s (mammary adenocarcinoma cells) and/or adipose-derived stromal cells (ADSCs), yielding an ideal 3D platform to evaluate adipocyte-breast cancer cell interactions. MCF-7s, pre-differentiated ADSCs, and a combination of both cell types were printed with an n=4. Cells were also cultured in 2D for comparison. Hydrogel properties such as degradation, swelling, and mechanical strength were evaluated to ensure optimal physical properties for printing ease and obtaining physiologically similar tissue properties. Rheological evaluation showed the resulting microtissue compressive moduli ranged from 16.74 to 75.95 kPa, indicating our ability to mimic stiffness of normal breast tissue and cancerous breast tissue, respectively. Viability testing consisting of Live/Dead, PicoGreen, and Alamar Blue showed that the cells were able to survive up to 12 days post-printing. Oil Red O staining demonstrated that the ADSCs were able to continue differentiation after being printed. This proof-of-concept study shows the potential for low-cost printing of multiple viable cell types in 3D structures mimicking the in vivo breast cancer environment. Future work includes testing the microtissues with different cancer treatments to evaluate tumor cell response in a 3D environment.
Funder Acknowledgement(s): Funding for this work was provided by University of Georgia Faculty Research Grant
Faculty Advisor: Cheryl Gomillion, ctgomillion@engr.uga.edu
Role: I conducted all of the research except for obtaining the rheometry data.