BENGALURU: Researchers from IISc have developed a low-cost, 3D-printed device that could help scientists understand why cancer drugs are less effective in deeper regions of solid tumours.The device recreates the nutrient- and oxygen-deprived conditions found inside tumours and allows researchers to examine how cancer cells respond to drugs at different depths.The platform, developed by researchers from IISc’s Department of Chemical Engineering, addresses a longstanding challenge in cancer research: reproducing the complex microenvironment of solid tumours in laboratory conditions while retaining access to cells from different regions for analysis.In solid tumours, blood vessels are often poorly developed and unevenly distributed.Consequently, cells closer to blood vessels receive more oxygen and nutrients, while those farther away experience shortages. These differences can influence how cancer cells grow and respond to treatment.Conventional laboratory methods that grow cancer cells in flat, two-dimensional layers do not adequately reproduce these conditions. One approach to overcoming this limitation is the ‘Cells-in-Gel-in-Paper’ (CiGiP) model, in which cancer cells embedded in a gel are grown on stacked paper layers.Nutrients and oxygen supplied from one side diffuse through the stack, creating conditions resembling different depths of a tumour. However, existing versions of this technique rely on wax-printed or hydrophobic barriers to contain the cell culture within each paper layer. The discontinuation of solid-ink printers, which were used for this purpose, has made the method less accessible to laboratories.The IISc team has replaced this requirement with a simple press-fit enclosure made using fused deposition modelling (FDM) 3D printers. Designed by Ankit Kumar, a PhD student in the laboratory of Bhushan J Toley, the device holds eight circular paper discs together through gentle, uniform pressure, preventing nutrients and drugs from leaking around their edges. Culture medium is supplied through an inlet at the top.The researchers tested the platform using MDA-MB-231 breast cancer cells embedded in Matrigel. After 72 hours, they found that the number of live cells progressively decreased from the topmost to the bottommost layer, while dead cells increased. Expression of HIF-1alpha, a gene associated with low-oxygen conditions, also rose towards the deeper layers, confirming that the model recreated a hypoxic tumour-like environment.The team then examined how the chemotherapy drug doxorubicin penetrated the tissue. Drug uptake declined progressively across the eight layers, indicating that deeper regions received less of the drug. Longer treatment periods partially overcame these diffusion limitations.
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The researchers also tested doxorubicin and paclitaxel, individually and in combination.Using a statistical method called the Bliss synergy score, they found that the two drugs had an antagonistic interaction across all eight layers when administered together. This means their combined effect was lower than what would be expected if the drugs acted independently.Published in Analytical Methods in 2026, the study was led by Toley, with Kumar and Shweta Kumar as co-authors. The researchers have made the device’s design files publicly available to facilitate reproduction.They believe the approach could make paper-supported 3D tumour models more accessible for drug screening and studies of treatment response.
