Laser direct-write based fabrication of a spatially-defined, biomimetic construct as a potential model for breast cancer cell invasion into adipose tissue.

Epithelial-adipose interaction is an integral step in breast cancer cell invasion and progression towards lethal metastatic disease. Understanding the physiological contribution of obesity, a major contributor to breast cancer risk and negative prognosis in post-menopausal patients, on cancer cell invasion requires detailed co-culture constructs that reflect mammary microarchitecture. Using laser direct-write, a laser-based CAD/CAM bioprinting technique, we have demonstrated the ability to construct breast cancer cell-laden hydrogel microbeads into spatially defined patterns in hydrogel matrices containing differentiated adipocytes. Z-stack imaging confirmed the three-dimensional nature of the constructs, as well as incorporation of cancer cell-laden microbeads into the adipose matrix. Preliminary data was gathered to support the construct as a potential model for breast cancer cell invasion into adipose tissue. MCF-7 and MDA-MB-231 breast cancer cell invasion was tracked over 2 weeks in an optically transparent hydrogel scaffold in the presence of differentiated adipocytes obtained from normal weight or obese patient tissue. Our model successfully integrates adipocytes and gives us the potential to study cellular and tissue-level interactions towards the early detection of cancer cell invasion into adipose tissue.

Directed self-assembly software for single cell deposition.

Laser direct-write (LDW) bioprinting methods offer a diverse set of tools to design experiments, fabricate tissue constructs and to cellular microenvironments all in a CAD/CAM manner. To date, we have just scratched the surface of the system's potential and for LDW to be utilized to its fullest, there are many distinct hardware and software components that must be integrated and communicate seamlessly. In this perspective article, we detail the development of novel graphical user interface (GUI) software to improve LDW capability and functionality. The main modules in the control software correspond to cell transfer, microbead fabrication, and micromachining. The modules make the control of each of these features, and the management of printing programs that utilize one or more features, to be facile. The software also addresses problems related to construct scale-up, print speed, experimental conditions, and management of sensor data. The control software and possibilities for integrated sensor data are presented.