What if testing cancer treatments no longer required extensive animal trials? Organ-on-chip technology is revolutionizing medical research by offering a more precise, ethical, and cost-effective way to study diseases and treatments.
In a recent study published in Advanced Materials Technology, a research team from the Netherlands introduced a novel injection-molded, modified silicone rubber designed specifically for cancer-on-chip applications.
They aimed to overcome the limitations of traditional materials and use this innovation to enhance cell culture compatibility and facilitate drug testing and screening in a controlled microfluidic environment.
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Cancer-on-Chip
Organ-on-chip (OoC) systems replicate human organ functions using living cells in a microfluidic environment, offering an alternative to animal testing for drug discovery. Cancer-on-chip (CoC) models, in particular, mimic tumor behavior, allowing researchers to study how cancer cells interact with drugs in a controlled setting.
These systems provide valuable insights into cell responses, biochemical gradients, and microenvironmental factors that influence tumor progression.
While CoC models hold great promise, their success depends on the materials used. Polydimethylsiloxane (PDMS) is commonly employed due to its flexibility and transparency, but its hydrophobic nature presents problems in cell adhesion and protein binding.
Unmodified PDMS can also absorb small molecules, affecting drug concentration and experimental accuracy. Researchers have explored chemical modifications to enhance PDMS functionality, but achieving stable, long-term improvements remains a challenge.
The Current Study
To address the challenges in CoC technology, this study introduced a modified silicone rubber with functionalized surfaces for improved compatibility in CoC applications. The researchers developed a modified silicone rubber for CoC applications using an injection molding process.
By incorporating covalently bound carboxyl groups into the PDMS surface, the team aimed to improve cell adhesion, protein binding, and compatibility with drug testing. They tested the hydrophilicity of the modified silicone by measuring water contact angles and using carboxyl groups to alter surface polarity.
To assess the material’s performance, the team cultured breast cancer cells and fibroblasts on the modified PDMS. Cell adhesion and proliferation were evaluated using fluorescence microscopy, 5-ethynyl-2'-deoxyuridine or EdU staining, and metabolic activity assays.
Additionally, the study integrated the modified PDMS into microfluidic inserts designed for the Micronit microfluidic system. The inserts contained fluidic channels and a porous membrane to allow nutrient flow and drug delivery.
Using this setup, researchers grew breast cancer cells on the inserts and tested doxorubicin, a chemotherapy drug. They analyzed cell viability and apoptosis through various methods to determine how the cells responded to treatment.
Finally, to assess the manufacturing potential of the modified silicone, the team also evaluated batch-to-batch variation and scalability. The injection molding process ensured high reproducibility, making large-scale production feasible.
Key Findings
The study found that the modified silicone rubber significantly improved cell adhesion and viability compared to standard PDMS. The introduction of carboxyl groups into the material facilitated stable protein coatings and enhanced the hydrophilicity, which is crucial for maintaining healthy cell cultures.
Furthermore, cancer cells exhibited greater proliferation rates on the modified surface, confirming its suitability for biological applications.
When integrated into a microfluidic system, the modified PDMS supported long-term breast cancer cell culture, mimicking the tumor microenvironment more effectively than traditional substrates. Cells grown on the modified inserts showed consistent nutrient absorption and waste removal, ensuring realistic physiological conditions for drug testing.
The drug screening experiments also demonstrated that the modified PDMS did not absorb doxorubicin, unlike unmodified PDMS, which can absorb the drug, reduce drug availability, and skew the results.
In tests with breast cancer cells, the modified CoC system required a lower drug concentration to achieve a significant apoptotic effect. Cells treated with doxorubicin exhibited a marked decrease in proliferation and a substantial increase in apoptosis, which reinforced the system’s effectiveness for drug testing.
A key limitation noted in the study was the current setup’s low throughput, limiting the number of simultaneous experiments.
However, the researchers suggested that scaling up production could enable high-throughput drug screening, also making the technology more viable for widespread adoption in personalized medicine.
Conclusions
Overall, the researchers presented an efficient CoC model in the form of an injection-molded, functionalized PDMS with promising applications in drug screening and testing. By improving cell adhesion and eliminating drug absorption issues, the modified silicone technology enhanced the accuracy of drug testing in microfluidic environments.
Although scalability remains a challenge, this innovation lays the groundwork for more effective, personalized cancer treatments. With further development, this CoC model could redefine drug screening and accelerate the adoption of organ-on-chip technologies in clinical research.
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