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Application of Channeled Hydrogel Scaffold as a Heart-on-a-chip System for Analyzing the Cardiotoxicity of Anticancer Drugs

Ranjbar, Ahmad | 2025

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 58245 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Mashayekhan, Shohreh
  7. Abstract:
  8. Cardiovascular diseases have been one of the leading causes of mortality in recent years. Therefore, the design and development of drugs for the prevention and treatment of heart diseases has always been one of the key strategies to combat these conditions. Traditional methods such as two-dimensional (2D) cell cultures and animal models are limited in their ability to accurately replicate the real structure of the human heart. In this regard, advancements in in vitro models aimed at better simulating physiological conditions have led to the development of heart-on-a-chip technology. In this study, by designing and fabricating a heart-on-a-chip model, the effect of the anticancer drug doxorubicin on H9c2 cardiac cells was investigated. To better simulate the three-dimensional cellular environment, a hydrogel based on oxidized alginate and decellularized extracellular matrix (ECM) from bovine heart tissue was used, which showed appropriate structural stability. Additionally, to create an internal channel within the chip, Pluronic F127 polymer was employed as a sacrificial ink. In this research, the response of cells to doxorubicin was compared between two different models: 2D cell culture and a dynamic heart-on-a-chip model. The results showed that dynamic flow significantly contributed to cell preservation and reduced drug-induced toxicity. Furthermore, the use of resveratrol as a pre-treatment led to a decrease in cell death and provided protection against doxorubicin. The results indicated that treatment with doxorubicin led to a 30% reduction in cell viability. However, pretreatment with resveratrol at concentrations of 25 and 50 micromolar resulted in a 20% and 26% increase in cell viability, respectively, in the groups cultured on the heart-on- a-chip platform. The findings of this study demonstrate the potential of the heart-on-a-chip model for drug toxicity evaluation and simulation of cardiac responses under conditions close to the human body. This approach may serve as an effective tool for cardiac drug screening in the future and help reduce the reliance on animal models
  9. Keywords:
  10. Heart-on-a-Chip ; Channeled Hydrogel Scaffold ; Doxorubicin ; Cardiotoxicity ; Three Dimentional Printing ; Extracellular Matrix ; Heart Diseases ; Pretreatment

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