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Investigating the Effect of Lymph Vessel Applying in Organ-On-A-Chip System to Improve the Biomimicry-Inspired Design Strategy

Deir, Sara | 2022

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 55780 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Yaghmaei, Soheila; Mashayekhan, Shohreh
  7. Abstract:
  8. In the last decade, the application of organ-on-chip systems to investigate the effectiveness and side effects of various drugs, modele diseases for different tissues has become noticed a lot because these systems are a promising approach to eliminate animal tests and clinical studies on different people. Current conventional methods for drug testing are expensive, time-consuming, and sometimes unreliable. Various organ-on-a-chip systems have been fabricated in order to mimic the conditions of different native tissues in the human body, but only the blood vessel has been considered in most of them while besides blood vessels, as a source to nourish cells, there are lymph vessels as a sink in which surplus of the interstitial fluid drain. Therefore, blood and lymph vessels together complete the microcirculation system of the vessels in the body. The aim of this project was to investigate the effect of sink channels on a heart-on-a-chip (HOC) response to doxorubicin (DOX) treatment. First, the equation of cell density was modeled considering the effect of doxorubicin on the survival of H9C2 cells, and based on simulation results, the structure of the chip was optimized and the distribution term of oxygen concentration, drug concentration, and cell density was obtained. Then, a hybrid hydrogel consisting of 4% alginate oxide, 0.8% extracellular matrix of decellularized calf heart tissue, 8% calcium carbonate, and 16% gluconodeltalactone (GDL) was prepared, and the H9C2 cells were encapsulated in the hydrogels. In order to improve the biomimicry of the heart-on-chip system, the difference between the permeability of the blood and lymph channels has been considered by adjusting the mesh size of the hydrogel in the wall of the channels. In the following, the chip was fabricated and the culture medium was circulated for 48 hours. The survival of cells in the chip was better than in 3D static sample. Cell survival in the dynamic system without lymph channel was 96% and for the system with lymph channel was 93.25%. After treatment with DOX drug, in general, the growth of cells decreased and the number of dead cells increased. The survival of cells in the dynamic system without lymph was 75.5% and the dynamic system with lymph was 81% because a part of the culture medium containing DOX drained from the hydrogel bulk into the lymph channel. In conclusion, considering lymph channels in HOCs is necessary in rder to improve the biomimicry of the system.
  9. Keywords:
  10. Heart-on-a-Chip ; Drug Testing ; Simulation ; Extracellular Matrix ; Organ on Chip ; Three Dimentional Printing ; Lymph Vessel ; Cardiotoxicity

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