Directed Three-Dimensional Growth of Microvascular Cells and Isolated Microvessel Fragments

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Abstract:

Tissue engineering has promise as a means for repairing diseased and damaged tissues. A significant challenge in tissue construction relates to the constraints placed on tissue geometries resulting from diffusion limitations. An ability to incorporate a premade vasculature would overcome these difficulties and promote construct viability once implanted. Most in vitro microvascular fabrication strategies rely on surface-associated cell growth, manipulated cell monolayers, or random arrangement of cells within matrix materials. In contrast, we successfully suspended microvascular cells and isolated microvessel fragments within collagen and then microfluidically drove the mixtures into microfabricated network topologies. Developing within the 3D collagen matrix, patterned cells progressed into cord-like morphologies. These geometries were directed by the surrounding elastomer mold. With similar techniques, suspended fragments formed endothelial sprouts. By avoiding the addition of exogenous growth factors, we allowed constituent cells and fragments to autonomously develop within the constructs, providing a more physiologically relevant system for in vitro microvascular development. In addition, we present the first examples of directed endothelial cell sprouting from parent microvessel fragments. We believe this system may serve as a foundation for future in vivo fabrication of microvascular networks for tissue engineering applications.

Keywords: Cell patterning; Microcirculation; Microvascular; Tissue engineering

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000006783981693

Affiliations: 1: Biomedical Engineering Program, University of Arizona, Tucson, AZ 85724, USA 2: Biomedical Engineering Program, University of Arizona, Tucson, AZ 85724, USA, Arizona Research Laboratories, University of Arizona, Tucson, AZ 85724, USA, The BIO5 Institute, University of Arizona, Tucson, AZ 85724, USA

Publication date: June 1, 2006

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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