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Collagen I Based Enzymatically Degradable Membranes for Organ-on-a-Chip Barrier Models.

ABSTRACT: Organs-on-chips are microphysiological in vitro models of human organs and tissues that rely on culturing cells in a well-controlled microenvironment that has been engineered to include key physical and biochemical parameters. Some systems contain a single perfused microfluidic channel or a patterned hydrogel, whereas more complex devices typically employ two or more microchannels that are separated by a porous membrane, simulating the tissue interface found in many organ subunits. The membranes are typically made of synthetic and biologically inert materials that are then coated with extracellular matrix (ECM) molecules to enhance cell attachment. However, the majority of the material remains foreign and fails to recapitulate the native microenvironment of the barrier tissue. Here, we study microfluidic devices that integrate a vitrified membrane made of collagen-I hydrogel (VC). The biocompatibility of this membrane was confirmed by growing a healthy population of stem cell derived endothelial cells (iPSC-EC) and immortalized retinal pigment epithelium (ARPE-19) on it and assessing morphology by fluorescence microscopy. Moreover, VC membranes were subjected to biochemical degradation using collagenase II. The effects of this biochemical degradation were characterized by the permeability changes to fluorescein. Topographical changes on the VC membrane after enzymatic degradation were also analyzed using scanning electron microscopy. Altogether, we present a dynamically bioresponsive membrane integrated in an organ-on-chip device with which disease-related ECM remodeling can be studied.

SUBMITTER: Arık YB

PROVIDER: S-EPMC8278385 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Invasive epithelial tumors form from cells that are released from their natural basement membrane and form 3-D structures that interact with each other and with the microenvironment of the stromal tissues around the tumor, which often contains collagen. Cancer cells, growing as monolayers on tissue culture plastic, do not reflect many of the properties of whole tumors. This shortcoming limits their ability to serve as models for testing of pharmacologically active compounds, including those that are being tested as antineoplastics. This work seeks to create new 3-D cellular materials possessing properties similar to those in native tissues surrounding cancers, specifically electrospun micro- and nanofibrous collagen scaffolds that support tumor growth in 3-D. We hypothesize that a 3-D culture system will provide a better replica of tumor growth in a native environment and, thus, better report the bioactivity of antineoplastic agents. In addition, we optimized conditions and identified physical characteristics that support growth of the highly invasive, prostate cancer bone metastatic cell line C4-2B on these matrices for use in anticancer drug studies. The effects of matrix porosity, fiber diameter, elasticity, and surface roughness on growth of cancer cells were evaluated. Data indicates that while cells attach and grow well on both nano- and microfibrous electrospun membranes, the microfibrous membrane represented a better approximation of the tumor microenvironment. It was also observed that C4-2B nonadherent cells migrated through the depth of two electrospun membranes and formed colonies resembling tumors on day 3. An apoptosis study revealed that cells on electrospun substrates were more resistant to both antineoplastic agents, docetaxel (DOC), and camptothecin (CAM) compared to the cells grown on standard collagen-coated tissue culture polystyrene (TCP). Growth, survival, and apoptosis were measured, as well as the differences in the apoptotic capabilities, of the two above-mentioned compounds compared to known clinical performance. We conclude that 3-D electrospun membranes are amenable to high throughput screening for cancer cell susceptibility and combination killing (Banerjee, S.; Hussain, M.; Wang, Z.; Saliganan, A.; Che, M.; Bonfil, D.; Cher, M.; Sarkar, F.H. Cancer Research, 2007, 67 (8), 3818-26).

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Collagen I Based Enzymatically Degradable Membranes for Organ-on-a-Chip Barrier Models.

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