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“BioArm” 3D Printer Builds Mini Tumors To Test New Immunotherapies

A fluoresence microscopy image of breast cancer cells, stained in multiple colors.
Breast Tumor Microenvironment. These breast cancer cells are stained with six primary antibodies to show areas of tumor in contrast to the supportive tissue (or stroma) and the tumor microenvironment. Stroma marked in green, red, and yellow; tumor in pink orange, and purple; and DNA is blue. Credit: Frank C. Marini/ National Cancer Institute
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Researchers have developed a 3D bioprinter – a machine that can print 3D structures using living cells and other biological materials – for cancer research.

The ‘BioArm’ was developed by researchers from the University of Cambridge and King’s College London, and can be folded, transported, transported and easily reassembled for printing. It can quickly manufacture complex tumouroids – 3D cell cultures that resemble tumour tissues – to test potential immunotherapy treatments.

Small, low-cost and lightweight (around 5kg), BioArm is based on a custom-built print head and a hackable robotic arm. It has an average print time of approximately 90 seconds per tumouroid. During the robotic arm movement, bio-ink – in this case a cell-laden hydrogel containing samples that simulate mice tumours – is extruded from the printhead to form the desired 3D soft material constructs on a petri dish.

Researchers studied the interaction between immune cells and the reconstructed tumouroids with cancer-associated fibroblasts (CAFs), and then subsequently simulated immunotherapy treatments. Details of their approach are reported in the journal Biofabrication.

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Immunotherapy uses the body’s immune system to identify and fight cancer cells. When it comes to in vitro cancer modelling for therapeutic testing, increasing efforts are being made to mimic the tumour microenvironment, which also include fundamental stromal components – an important part of the body’s immune response. Animal models are frequently used to assess new treatment methods in cancer research, but modelling a tumour in vitro could help reduce animal model use in the future.

Due to its precision and reproducibility, 3D bioprinting is a valuable tool to help construct in vitro cancer models of this nature, but most existing bioprinters are difficult to move around or reassemble. BioArm, in comparison, has been designed to be portable, and can be assembled and disassembled within 15 minutes.

To assess if BioArm’s 3D printed compartmental tumouroids could be used to test potential therapies as part of drug discovery pipelines, the researchers used live cell imaging and image analysis to study immune cell migration. This was conducted in 3D collagen gels in the presence of the tumouroid. High-resolution imagery successfully captured the immune cells infiltrating the 3D printed tumouroids, with the immune cells stimulated with immunotherapy moving noticeably faster.

“BioArm, with its portability and ease of use, has the potential to make 3D bioprinting accessible to a wider research community,” said co-first author Yaqi Sheng, PhD student in the Biointerface Research Group at the Department of Engineering, University of Cambridge. “This bioprinter has broken new ground; it can readily adapt to different working environments, while preserving relatively high accuracy. Its adaptability, flexibility and biological relevance has not yet been shown by existing low-cost and open-source bioprinters.”

Corrado Mazzaglia, first author of the paper and Research Associate in the Biointerface Research Group, added: “Bioprinted cancer models mimic the 3D heterogeneity of real tumours. BioArm has the potential to screen a wide range of tumour therapies and could play a crucial role in the future development of cancer drug testing approaches.”

Reference: Mazzaglia C, Sheng Y, Rodrigues LN, Lei IM, Shields JD, Huang YYS. Deployable extrusion bioprinting of compartmental tumoroids with cancer-associated fibroblasts for immune cell interactions. Biofabric. 2023;15(2):025005. doi: 10.1088/1758-5090/acb1db

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