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Design and Fabrication of a Microfluidic Device for the Formation of Multicellular Aggregates and Using in Tissue Engineering

Salehi, Sarah | 2020

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 53704 (08)
  4. University: Sharif University of Technology
  5. Department: Mechanical Engineering
  6. Advisor(s): Shamloo, Amir; Kazemzadeh, Siamak
  7. Abstract:
  8. Three-dimensional cell culture and forming multicellular aggregates is superior over traditional monolayer approaches due to better mimicking in vivo conditions and hence functions of a tissue. A considerable amount of attention has been devoted to devising efficient methods for the rapid formation of uniform sized multicellular aggregates. Restoring cartilage to healthy state is difficult due to low cell density and hence low regenerative capacity. Currently used platforms are not compatible with clinical translation and require dedicated handling of trained personnel. However, when engineering and implanting cell microaggregates in a higher concentration, new cartilage is efficiently formed, even in the absence of exogenous growth factors. So one-step surgeries are preferable for novel treatments and we need cell laden microgels allowing the formation of microaggregaets in vivo. Conventionally methods to form microaggregates during 24 hours prevent this. Injectable hydrogels can be considered as bioinks to form the shape of a damaged tissue. Microfluidics technology is known as a group of platforms comprising of microchannels to manipulate the small number of reagents with unique properties and capabilities suitable for biological studies. In this work we propose to circumvent steps allowing formation of microaggregates within the patient body, both numerically and experimentally. Droplet-based microfluidics might be used to form microgels as carriers for delivering cells and biological cues to the target tissue minimally invasive. Stem cell-laden microgels with a shape forming property as smart building blocks can be injected to the injured tissue and form the shape of damaged tissue as bioinks. We tried to form three dimensional tissues with the aid of droplet based microfluidics and forming uniform sized stem cell aggregates. Embedding microgels containing micro-aggregates of stem cells within collagen scaffold showed that the shape of the scaffold didn’t change five weeks post encapsulation and confirms the shape forming capability of HA-TA microgels filling collagen matrix. Implementing this idea for transferring cells to the damaged tissue and in vivo conditions helps generating new cartilage tissue
  9. Keywords:
  10. Microfluidic Devices ; Enzymatic Crosslinking ; Injectable Hydrogel ; Cell Culture ; Tissue Engineering ; Multicellular Aggregates

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