Design and Optimization of Channeled Hydrogel Scaffold Based on Extracellular Matrix of Heart Tissue with Oxygen Release Capability

Ghasemi, Sara | 2022

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 55425 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Mashayekhan, Shohreh; Khorshidi, Sajedeh
  7. Abstract:
  8. Despite the increase in the number of cardiovascular diseases worldwide, the number of new drugs to treat these diseases has been decreasing in the last decade. Current preclinical drug evaluation strategies, which use cell cultures and oversimplified animal models, cannot meet the growing demand for new and effective drugs. In the last decade, the development of microfluidic bioreactors and organ-on-chip systems to improve the drug screening process has been increasing significantly. These systems have shown many advantages over previous preclinical models. Despite all these advantages, keeping the oxygen concentration at the optimal physiological level in microfluidic systems has its own challenges. Creating microfluidic channels is one of the solutions provided to solve this challenge. Although this method is useful, it is not an effective way to deliver oxygen to the cultured cells. Due to the small size of the microfluidic channels, oxygen supply to the cells is limited by this method and cannot meet the metabolic needs of the cells. In this research, for the first time, we have used oxygen-producing materials in order to solve the challenge of oxygen deficiency in microfluidic systems. Finally, the goal of this project is to develop a heart-on-chip that can be used as a model for drug screening. First, the release of oxygen by hydrogen peroxide in a hydrogel containing microfluidic channels was simulated and the effect of its presence on the distribution of oxygen concentration and cell density was investigated. By analyzing the simulation results, the single branch structure with the initial hydrogen peroxide of 15 mol/m3 was chosen as the optimal condition. The used supporting hydrogel is a combination of oxidized alginate (5% oxidation degree) decellularized extracellular matrix of calf heart tissue and oxygen-producing microparticles. Using bioprinting, sacrificial Pluronic F-127 ink created hollow channels within the supporting hydrogel. The synthesized support hydrogel was characterized by FTIR and SEM tests. The oxygen-producing microparticle was synthesized using the double emulsion method and its characterization was done by hydrogen peroxide release measurement, oxygen release measurement, loading efficiency measurement, and SEM. The results of oxygen release measurements show that the synthesized microparticles have the ability to release oxygen sustainably for at least 10 days. Finally, the developed bioreactor system was tested in the laboratory in terms of creating microfluidic channels, sealing, and non-leakage.
  9. Keywords:
  10. Biomaterials ; Extracellular Matrix ; Bioprint ; Three Dimentional Printing ; Heart Tissue Engineering ; Drug Screening ; Oxygen Generating Biomaterials ; Heart-on-a-Chip

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