Abstract 4828: Recapitulating mammary ductal carcinoma microenvironment in vitro using sacrificial bioprinting
Authors: Zhang Y. Shrike , Duchamp Margaux , Ellisen Leif W. , Moses Marsha , Khademhosseini Ali 
Published: July 2017

American Cancer Society projects that 1,685,210 new cancer cases will be diagnosed and 595,690 death will occur in 2016, corresponding to about 1,600 deaths per day. In 2016, an estimated 246,660 and 2,600 new cases of invasive breast cancer (e.g. invasive ductal carcinoma) are expected to be diagnosed in women and men in the U.S., respectively, along with 61,000 new cases of non-invasive (i.e., in situ) breast cancer for women. Although tremendous improvements in breast cancer survival have been achieved, current drug administration procedures relying on chemotherapy followed by radiographic scans often lead to disparity in cancer care, necessitating the development of predictive models that can achieve personalized drug administration regimes. While patient-derived tumor graft models have achieved some success, the genetic difference between animal species and the human remains a critical barrier for accurate prediction of patient responses, in addition to their overly high cost. During the past few years, the organs-on-a-chip technologies have made tremendous progress thanks to their capability in modeling the physiology of the sophisticated human systems. Such capability has been further enhanced by advancements in tissue engineering and bioprinting, making it possible to recapitulate the architecture and functionality of tissues in vitro. Here we have utilized a sacrificial bioprinting strategy to generate biomimetic mammary duct-like structures within a hydrogel matrix, to model the genesis and of ductal carcinoma and its invasion. Sacrificial bioprinting has proved its utility in fabricating hydrogel constructs containing hollow microchannels mimicking the tubular structures in the human body. In a typical process we first deposit a mold consisting of sacrificial microfibrous structures using Pluronic from a computerized model and allow it to dry overnight; we subsequently fill the mold with a mixture of gelatin methacryloyl (GelMA)/collagen I solution and induce gelation using photocrosslinking; afterwards, the Pluronic fillers are removed by immersing the entire construct in a cold phosphate buffered saline to achieve hydrogel microchannels. These bioprinted microchannels could then be populated with mammary ductal carcinoma cells on their interior walls. The cells were able to proliferate and populate the surface of the microchannels in 3 weeks, followed by initiation of invasion from the microchannels into the surrounding matrix in the 4th week of culture. In the meantime the cells were observed to deposit basement membrane molecules such as collagen type IV. This bioprinted mammary ductal carcinoma model provides a proof-of-concept demonstration of using bioprinting technologies for engineering biologically relevant cancer models, which can be readily extended to other cancer types where duct-like structures are involved.

Citation Format: Y. Shrike Zhang, Margaux Duchamp, Leif W. Ellisen, Marsha Moses, Ali Khademhosseini. Recapitulating mammary ductal carcinoma microenvironment in vitro using sacrificial bioprinting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4828. doi:10.1158/1538-7445.AM2017-4828