Scientists from Portugal and Japan have reviewed the recent advances and perspectives on organ-on-a-chip platforms. Their research is currently in the pre-proof stage in the journal Bioprinting.
Study: Recent trends of biomaterials and biosensors for organ-on-chip platforms. Image Credit: Gorodenkoff/Shutterstock.com
What are Organ-on-a-Chip Platforms?
The importance of developing drugs, therapies, and diagnostic strategies for diseases has driven innovative technological solutions in the field of biomedical science. Amongst currently proposed technologies, organ-on-a-chip platforms have emerged as cutting-edge solutions.
Organ-on-a-chip platforms mimic human organs and are devices where cell cultures are incorporated into microfluidic devices. Microfluidic devices confer several advantages for clinical research, including miniaturization, high-throughput analysis, enhanced sensitivity, reduction in reagents, and improved analytical performance.
First reported in 2010 with the development of a lung, there have been several other organ-on-a-chip platforms reported in the literature over the past decade. Organ-on-a-chip platforms confer advantages for clinical research over conventional static 2D cell cultures as they mimic the 3D microenvironment and interactions between cells which occur in the human body. They have been successfully used to replicate physiological functions such as muscle contraction, gas exchange, and electrical stimulation.
These innovative devices also help avoid the ethical issues that arise with using animal and human models. Additionally, using organ-on-a-chip platforms address the challenges caused by interspecies differences, especially in the case of anticancer drug development, which animal models are unsuitable for. Recent studies have developed placenta, blood-brain barrier, blood-retina barrier, tooth, liver, heart, bio-artificial tongue, tumor, and tumor-vascular-on-a-chip platforms.
Organ-on-a-chip platforms are a low-cost, fast alternative to conventional drug, treatment, and intervention development strategies. They provide enhanced drug toxicity and efficacy analysis and help evaluate the progression of disease in different organs more effectively than alternative strategies. The development and optimization of these devices also contribute to improvements in novel technologies such as bioprinting.
Polydimethylsiloxane is the preferred material for the manufacture of these microfluidic devices. Advantages of this material include its easy handling and unique physiochemical properties. Properties include good transparency, chemical inertness, good thermal stability, gas permeability, and low interfacial free energy on the surface of the material.
Polydimethylsiloxane is also biocompatible, relatively non-toxic, durable, hydrophobic, and bioinert. Despite this, there are some problems with the material. It can leach un-crosslinked oligomers and absorb hydrophobic molecules.
Leaching of un-crosslinked oligomers is especially problematic for cell cultures as it can cause toxicity in cells and alter their behavior. Therefore, the need for more suitable materials to replace polydimethylsiloxane or materials which can be used in conjunction with it has become a research focus in recent years, and several biomaterials have been explored. Studies have also investigated surface treatments to reduce the drawbacks of polydimethylsiloxane.
The authors have compiled several current trends in research into new materials for use in the manufacture of organ-on-a-chip platforms. The authors have investigated several studies in the current literature.
In the study, there is a brief overview of how polydimethylsiloxane is synthesized and an exploration of strategies to overcome problems with cell adhesion typically faced by researchers during the fabrication of organ-on-a-chip platforms, such as coating the polydimethylsiloxane chambers with proteins and other organic compounds.
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For example, systems that mimic the blood-brain barrier are coated with laminin on one side and a composite coating of collagen IV/fibronectin on the other. This improves the seeding of cells and differentiation of the blood and brain sides of the barrier. Other studies have used low-pressure air plasma treatments to improve the platform’s hydrophilicity, with the porous membrane fluorinated to make it more hydrophobic. Several treatments have been explored to improve cell seeding on the surface of devices.
Devices that combine polydimethylsiloxane and other materials have been presented in the research. A device for testing cancer drugs was devised by coating two poly(methylmethacrylate) substrates with polydimethylsiloxane. This enhanced sealing during the tests. Furthermore, the devices were impregnated with neodymium magnets to reverse the sealing, which allowed for the retrieval of tumor samples for further analysis.
Other research highlighted in the review which utilized different materials was a study on using polycaprolactone-coated fibers embedded in polydimethylsiloxane layers. The same study reported the fabrication of polycaprolactone microtubes using core-sheath electrospinning. Both methods reported in the study effectively mimicked human capillaries. Other materials reported include polyester and carbon-nanoparticle chitosan composites.
Using alternative materials not only enhances organ-on-a-chip devices but also allows the formulation of morphological features that mimic the phenotypes found in humans, contributing to the cell culture’s development. Some can be used as sacrificial features. However, challenges can arise from residues of sacrificial materials, warranting further exploration of novel strategies in the future.
Furthermore, the authors have explored both the materials used in the system’s components alongside the different sensors added to devices as detection systems, providing a perspective on end-use. Types of sensors reviewed include sensors to monitor the cell culture’s microenvironment, sensors that monitor cell behavior and activity, and other detection systems, such as miniaturized versions of laboratory equipment.
Finally, the authors have stated that recent advances in the field demonstrate the potential of organ-on-a-chip devices to replace the current gold standard of 2D platforms used in clinical studies and can help realize a more patient-specific personalized medical research paradigm.
Gonçalves, I.M et al. (2022) Recent trends of biomaterials and biosensors for organ-on-chip platforms [pre-proof] Bioprinting e00202 | sciencedirect.com. Available at: https://www.sciencedirect.com/science/article/pii/S2405886622000124