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DESIGN, FABRICATION AND CHARACTERIZATION OF BIFURCATING MICROFLUIDIC NETWORKS FOR TISSUE-ENGINEERED PRODUCTS WITH BUILT-IN MICROVASCULATURE

Janakiraman, Vijayakumar

Abstract Details

2008, Doctor of Philosophy, Case Western Reserve University, Chemical Engineering.
Current tissue-engineered (TE) products face the fundamental limitation of inadequate supply of nutrients from the host blood vessels to the implanted cells. Several strategies including porous scaffolds, hydrogels, and angiogenic factor delivery, have been employed to address the nutrient limitations. However these strategies fail to overcome the problem as nutrient mass transfer primarily occurs by passive diffusion until the product is vascularized in vivo through angiogenesis. An ideal TE product will feature a built-in microvasculature, leading to convective delivery of nutrients, thus eliminating this mass transfer limitation. The primary goal of this work is to design and develop bifurcating microfluidic networks with optimal transport characteristics to be integrated within natural biodegradable scaffolds for TE products. An optimization model is developed to maximize the mass transfer efficiency of micron-scale planar bifurcating networks, and solved using the generalized reduced gradient (GRG) algorithm. The effects of network variables such as number of generations and porosity on the efficiency of the network designs are studied. Numerical simulations of oxygen concentrations in the tissue, a parameter indicative of tissue function, are carried out to verify our approach to determine network efficiency. Using standard photo/soft lithography techniques, the network designs are obtained in poly-dimethyl siloxane (PDMS) molds. Subsequently, microfluidics is established in the PDMS networks and frictional resistances of the networks and flow rates in individual channels of the networks are measured experimentally. The pressure drop-flow rate relationship and the flow distribution efficacy of the networks are quantified and compared with analytical and numerical estimates. A novel surface patterning technique is developed to fabricate the optimal network designs in a natural and biodegradable scaffold material made of collagen-glycosaminoglycans (CG). Endothelial cells are seeded within the CG flow channels and the attachment and growth of these cells in the channels are studied. The endothelialized flow networks will function as the built-in microvasculature for a TE construct by efficiently delivering nutrients and removing waste products from the construct. Ultimately, this can be used as the basis for a generalized approach for tissue-engineering of three dimensionally complex organs such as liver, heart and kidney with a built-in microvasculature.
Harihara Baskaran (Advisor)
263 p.

Recommended Citations

Citations

  • Janakiraman, V. (2008). DESIGN, FABRICATION AND CHARACTERIZATION OF BIFURCATING MICROFLUIDIC NETWORKS FOR TISSUE-ENGINEERED PRODUCTS WITH BUILT-IN MICROVASCULATURE [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1196457966

    APA Style (7th edition)

  • Janakiraman, Vijayakumar. DESIGN, FABRICATION AND CHARACTERIZATION OF BIFURCATING MICROFLUIDIC NETWORKS FOR TISSUE-ENGINEERED PRODUCTS WITH BUILT-IN MICROVASCULATURE. 2008. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1196457966.

    MLA Style (8th edition)

  • Janakiraman, Vijayakumar. "DESIGN, FABRICATION AND CHARACTERIZATION OF BIFURCATING MICROFLUIDIC NETWORKS FOR TISSUE-ENGINEERED PRODUCTS WITH BUILT-IN MICROVASCULATURE." Doctoral dissertation, Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1196457966

    Chicago Manual of Style (17th edition)