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Design of Amniotic Membrane-based Hydrogel for Cardiac Tissue Engineering Application

Gholami, Bahar | 2022

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 55412 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Yaghmaei, Sohila; Saadatmand, Maryam
  7. Abstract:
  8. Mammalian cardiac tissue lacks the ability to effectively self-regenerate following severe damage. The application of external therapeutic agents with strong mechanical properties is needed to restore its function. Even though conventional therapies have several challenges and limitations, injectable hydrogels, with minimally invasive, can significantly improve cardiac tissue regeneration. Extracellular matrices are the most appropriate biomaterials for synthesizing cardiac scaffolds. The human amniotic membrane obtained from the amniotic sac is a readily available, abundant, and inexpensive candidate that has been successfully utilized for the clinical treatment of cardiac diseases. Decellularized amniotic membrane has very low immunogenicity and better cellular response. In this study, we designed a decellularized amniotic membrane-based injectable hydrogel with improved mechanical properties for cardiac tissue engineering application. For this purpose, decellularization was carried out by sodium dodecyl sulfate and ethylenediaminetetraacetic acid with mechanical scraping. And digestion was done by pepsin. Histological tests performed on fresh and decellularized samples showed that with 97.5% DNA removal, the structure and main components of the matrix were retained intact. Alginate was oxidized by sodium metaperiodate. Infrared spectroscopy confirmed the formation of chemical crosslink resulting from Schiff-base reaction between collagen of amniotic membrane and aldehyde group of this natural polymer. Also, ionic crosslinking of alginate oxide by calcium ions resulted in acceptable mechanical strength of hydrogel. Combining calcium carbonate and calcium sulfate controlled the gelation rate of the hydrogel. The gelation time measurements and rheology analysis showed that hydrogels with calcium sulfate: calcium carbonate molar ratio of 0.25: 0.75, calcium ion to the mannuronic group of alginate oxide molar ratio of 3.5X (X=0.18), and alginate oxide concentrations of 2% and 3% formed in about 5.5 and 12.5 min. They had significantly higher storage modulus compared to just injectable amniotic membrane matrix. (At 1% strain and frequency in the range of 0.1-10 Hz, the storage modulus reached 100 and 350 Pa). Hydrogels showed acceptable swelling behavior and degradation rate. (Average weight change of hydrogels were about 60% and 70% after a day. They degraded in vitro within 5 & 7 days of incubation in PBS solution.) On the other hand, another fetal membrane part called the chorionic membrane was used to synthesize this hydrogel because of its notable composition and its ability to improve cell proliferation in soluble form. Chorionic membrane-based hydrogel showed similar behavior in forming bonds with alginate oxide, gelation time, rheological properties, swelling, and degradation rate
  9. Keywords:
  10. Double Network Hydrogel ; Injectable Hydrogel ; Oxidized Alginate ; Heart Tissue Engineering ; Schiff-Base Interaction ; Human Fetal Membrane ; Ionic Crosslink

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