Tissue engineered (TE) products have the potential to revolutionize health care. A number of tissues and organs in the human body such as cartilage, bones, heart valves, blood vessels, skin and liver are being investigated as targets for tis- sue engineering. However, only a handful of them such as TE skin are currently in clinical use. In addition, almost all TE products currently in use or undergoing clinical trials are targeted at avascular tissues (e.g. heart valves and carti- lage), or are not vascularized before their use in the clinics (e.g. skin substitutes). A major obstacle in the application of TE engineering to target tissues of higher function is the lack of a general approach to develop TE products with inte- grated microvascular system for convective delivery of nutrients and removal of metabolic waste products. Our strategic goal is to develop such an approach. In this proposal, we describe a method to build 'vascularized' TE skin constructs. We propose four specific aims, which address several specific issues that range from mass transfer requirements of tissues to fabrication, and in vitro testing of tissues with built-in capillary flow networks. These are:
Specific Aim 1. To assess mass transfer requirements of cells, using microfabrication and microfluidic methodologies. This will lead to subsequent rational design of the capillary flow networks and to better understanding of mass transfer limita- tions in tissue constructs.
Specific Aim 2. To design and fabricate optimal planar microvascular analog systems in biopolymeric matrices. In this specific aim, optimal capillary networks designs tailored to meet the metabolic demand of target tissue will be embedded in collagen-glycosaminoglycans (collagen-GAG) to form scaffolds for microvascula- ture using microfabrication methodologies.
Specific Aim 3. To 'vascularize' capillary networks by endothelializa- tion and by microfluidics, and to assess them in vitro. This will lead to collagen-GAG scaffolds with 'microvascular' networks that can supply nutrients and remove waste products via convective means.
Specific Aim 4. To develop composite TE skin in a perfusion bioreactor and to assess the efficacy of an integrated convective transport sys- tem on the growth and differentiation of composite TE skin. In this specific aim, composite skin substitutes with integrated flow networks will be developed in a perfusion bioreactor to test the hypothesis that convective transport of substrate improves the rate of formation of a differentiated epidermis. Successful completion of these aims will result in a product that is scalable and that can readily be tested in vivo. ? ?

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
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Musculoskeletal Tissue Engineering Study Section (MTE)
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Hunziker, Rosemarie
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Case Western Reserve University
Engineering (All Types)
Schools of Engineering
United States
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Wang, Kevin; Wang, Joanne H; Baskaran, Harihara et al. (2012) Effect of human beta-defensin-3 on head and neck cancer cell migration using micro-fabricated cell islands. Head Neck Oncol 4:41
Toy, Randall; Hayden, Elliott; Shoup, Christopher et al. (2011) The effects of particle size, density and shape on margination of nanoparticles in microcirculation. Nanotechnology 22:115101
Maeda, Toru; Sakabe, Tomoya; Sunaga, Ataru et al. (2011) Conversion of mechanical force into TGF-?-mediated biochemical signals. Curr Biol 21:933-41
Sarkar, Saheli; Bustard, Bethany L; Welter, Jean F et al. (2011) Combined experimental and mathematical approach for development of microfabrication-based cancer migration assay. Ann Biomed Eng 39:2346-59
Mazzoccoli, Jason P; Feke, Donald L; Baskaran, Harihara et al. (2010) Mechanical and cell viability properties of crosslinked low- and high-molecular weight poly(ethylene glycol) diacrylate blends. J Biomed Mater Res A 93:558-66
Mazzoccoli, Jason P; Feke, Donald L; Baskaran, Harihara et al. (2010) Development of multilayered cell-hydrogel composites using an acoustic focusing technique. Biotechnol Prog 26:600-5
Liang, Wan-Hsiang; Kienitz, Brian L; Penick, Kitsie J et al. (2010) Concentrated collagen-chondroitin sulfate scaffolds for tissue engineering applications. J Biomed Mater Res A 94:1050-60
Breckenridge, Mark T; Egelhoff, Thomas T; Baskaran, Harihara (2010) A microfluidic imaging chamber for the direct observation of chemotactic transmigration. Biomed Microdevices 12:543-53
Sarkar, Saheli; Egelhoff, Thomas; Baskaran, Harihara (2009) INSIGHTS INTO THE ROLES OF NON-MUSCLE MYOSIN IIA IN HUMAN KERATINOCYTE MIGRATION. Cell Mol Bioeng 2:486-494
Janakiraman, Vijayakumar; Sastry, Sudeep; Kadambi, Jaikrishnan R et al. (2008) Experimental investigation and computational modeling of hydrodynamics in bifurcating microchannels. Biomed Microdevices 10:355-65

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