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A Heart-On-A-Chip Platform Containing Channeled Hydrogel for Drug Testing

Abdi, Azadeh | 2024

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 56925 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Mashayekhan, Shohreh
  7. Abstract:
  8. Cardiovascular diseases are one of the leading causes of death worldwide. Despite significant advances in therapeutic interventions for these diseases, the pathophysiology remains incompletely understood. Challenges in drug evaluation include the lack of appropriate clinical trials, such as conventional 2D cell cultures and animal studies, as well as the absence of model systems that can provide complex and patient-specific cardiac functions for diagnosis. Organ-on-a-chip devices have the potential to mimic the body's response to treatments by utilizing microscale cell culture fluid connections and creating realistic models of human organs of interest. Our objective is to develop a heart-on-a-chip model using a channeled hydrogel scaffold with a blood vessel-inspired structure. The aim is to demonstrate the cardiotoxicity effect of the anticancer drug doxorubicin in young and old subjects. To achieve this, we utilized a hybrid hydrogel composed of collagen to mimic heart tissue, and alginate to enhance mechanical properties, as the cell-containing hydrogel scaffold. The vascular structure was printed using the FRESH v2.0. To improve the biomimicry of the heart-on-a-chip system and replicate the stiffness and mechanical properties of the native tissue, the difference between old (approximately 40 kPa) and young (approximately 10 kPa) tissue was taken into account. In order to assess cell viability in the presence and absence of doxorubicin, we cultured old and young cells dynamically on a hydrogel scaffold with the appropriate stiffness. To simulate the cells in old heart tissue, H9C2 cells have been treated with D-galactose. The observed cell survival rate in static culture was approximately 2% lower compared to dynamic culture, attributable to the absence of nutritional channels within the hydrogel bulk. Notably, the toxicity of doxorubicin on aged H9C2 cells embedded in hydrogel with a higher compressive modulus (mimicking old heart tissue) was approximately 10% lower than that observed in young cells embedded in hydrogel with a lower compressive modulus (representative of young heart tissue). This system presents an effective approach for exploring the impact of aging on drug efficacy within a heart tissue model, distinguishing between the responses of young and old individuals
  9. Keywords:
  10. Heart-on-a-Chip ; Doxorubicin ; Drug Testing ; Freeform Reversible Embedding of Suspended Hydrogels (FRESH)Method ; Three Dimentional Printing ; Hydrogel Scaffold ; Channeled Hydrogel Scaffold

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