Novel Collagen Membrane Improves Colon-on-a-Chip Functionality
Article May 23, 2018 | By Sonali Karnik, PhD
Inflammatory bowel disorders (IBDs) such as Crohn’s disease are caused by complex interactions between intestinal cells, cytokines, and gut microbiota. Different treatment modalities and drugs for IBDs are less effective in some patients than others. This unpredictability of response to drugs in some patients can be attributed to that person’s unique physiology and gut microenvironment.
For understanding the interactions between intestinal cells and cytokines, there is a need to have efficient physiologic models that can replicate the niche environment of the gut. While rodents are extensively used as animal models for studies involving gut and drug interactions, due to the differences in the rodent and human physiology these animal models do not reflect the complex human gut niche.
Microfluidic tissue-chips can replicate the complex tissue microenvironment and can be engineered according to the testing needs. These tissue systems can be regulated and controlled better when conducting experiments. The existing microfluidic gut-on-a-chip models use either PDMS (Polydimethylsiloxane) or PDMS combined with other synthetic materials such as Poly- L- Lactic Acid (PLLA). Even though these materials have been found to support cell growth, there are some undesired effects observed such as the cells developing a non-physiologic squamous epithelium instead of columnar which is the type observed in vivo. These membranes also have non-physiological pores which span several micrometers restricting cellular movement across the barrier.
Our objective was to build a microfluidic model of colon using natural tissue base matrix or extracellular matrix made from collagen type I to closely mimic the structure and function of the colon and which can be used to study the complex interaction of the cellular components and drug metabolism.
What makes our microfluidic colon-on-a-chip unique is the membrane made from natural base matrix material used to support cells in the device. Using collagen type I instead of a synthetic material replicates the niche environment in the native tissue. We tested our devices with this novel collagen membrane for cell viability, functionality, and mass transport of nutrients across the membrane barrier to see if this membrane improved cellular function when compared to the devices made with commercially available Transwell membranes. Our findings suggest that the devices with collagen type I membrane had better and extended viability of the human gut cells, retention of morphology, function, as well as barrier function.
Our device having two separate chambers with the collagen matrix can be used for co-cultures of different cells with gut cells. We can see our collagen membrane based colon-on-a-chip model as an efficient tool to help to predict the response of gut cells to different effectors such as gut microorganisms, drugs, and cytokines helping in the drug discovery process.
Wang, C., Tanataweethum, N., Karnik, S., & Bhushan, A. (2018). Novel Microfluidic Colon with an Extracellular Matrix Membrane. ACS Biomaterials Science & Engineering, 4(4), 1377-1385. doi:10.1021/acsbiomaterials.7b00883
The development of new in vitro models to replace in vivo testing has already proven quite successful for certain targets. Among these are models of the immune system and human skin, while in vitro cardiac arrhythmia models are poised to emerge in the near future. Despite this clear progress, an efficient model for liver organ toxicity testing still remains elusive.READ MORE