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A Microfluidic Approach to Tissue Vascularization

Boyang Zhang

出版	University of Toronto, 2016
URL	http://books.google.com.hk/books?id=66A-zwEACAAJ&hl=&source=gbs_api

註釋

From the inception of tissue engineering, tissue vascularization has been one of the greatest challenges in this field. Our inability to capture the daunting complexity of this natural biological system has slowed down the advancement of this field. But the emergence of microfluidic technology/micro-fabrication has expanded engineers' toolbox, allowing us to create structures that are as small as a capillary and as complex as a vascular bed. My thesis hypothesis is that functional, high-density tissues can be vascularized by microfluidic bio-scaffolds based on synthetic biodegradable polymer with built-in, endothelialized, permeable 3-D vascular networks. The synthetic vessel network is also mechanically stable enough to establish immediate blood perfusion upon implantation by direct surgical anastomosis. Successful development of a robust vascularization strategy would serve as the foundation to both further advance tissue engineering in clinical application as well as establish a more complete in-vitro model for drug discovery. In the first specific aim, we established a protocol for culturing endothelial cells in small conduit such as a PDMS networks with circular channel cross-sections. In these micro-networks, endothelial cells naturally coat the inner luminal surface and form tubular structure with tight-intercellular junction. However, PDMS is not an implantable material and also does not allow us to incorporate a parenchymal space. Then in the following specific aims, we established a 3-D stamping technique to create a bio-scaffold with build-in micro-channel network that is mechanical stable, yet permeable and permits intercellular crosstalk and extravasation of monocytes and endothelial cells on biomolecular stimulation through the incorporation of nano-pore and micro-holes on the channel walls. With this technology (hereafter referred to as AngioChip), we successfully engineered vascularized functional rat and human hepatic and cardiac tissues that can process clinically relevant drugs delivered through the vasculature. Furthermore, millimetre-thick cardiac tissues can be engineered in a scalable manner. Finally, we demonstrated direct surgical anastomosis of the engineered tissues in both artery-to-artery and artery-to-vein configuration.