Perfusion systems that minimize vascular volume fraction in engineered tissues.

This study determines the optimal vascular designs for perfusing engineered tissues. Here, "optimal" describes a geometry that minimizes vascular volume fraction (the fractional volume of a tissue that is occupied by vessels) while maintaining oxygen concentration above a set threshold throughout the tissue. Computational modeling showed that optimal geometries depended on parameters that affected vascular fluid transport and oxygen consumption. Approximate analytical expressions predicted optima that agreed well with the results of modeling. Our results suggest one basis for comparing the effectiveness of designs for microvascular tissue engineering.

[1]  M Zamir,et al.  Optimality principles in arterial branching. , 1976, Journal of theoretical biology.

[2]  Vijayakumar Janakiraman,et al.  Optimal Planar Flow Network Designs for Tissue Engineered Constructs with Built-in Vasculature , 2007, Annals of Biomedical Engineering.

[3]  D. Kohane,et al.  Engineering vascularized skeletal muscle tissue , 2005, Nature Biotechnology.

[4]  David J Mooney,et al.  Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones , 2010, Proceedings of the National Academy of Sciences.

[5]  J. Sloane,et al.  Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast , 2002, British Journal of Cancer.

[6]  Pao C. Chau,et al.  Modeling of Axial‐Flow Hollow Fiber Cell Culture Bioreactors , 1996 .

[7]  A. Veitch,et al.  Oxygen transfer in a diffusion-limited hollow fiber bioartificial liver. , 2000, Artificial organs.

[8]  G. Westbury,et al.  The vascularity of cutaneous melanoma: a quantitative histological study of lesions 0.85-1.25 mm in thickness. , 1991, British Journal of Cancer.

[9]  C. D. Murray THE PHYSIOLOGICAL PRINCIPLE OF MINIMUM WORK APPLIED TO THE ANGLE OF BRANCHING OF ARTERIES , 1926, The Journal of general physiology.

[10]  H. Blau,et al.  Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. , 2004, The Journal of clinical investigation.

[11]  B. Dale,et al.  Optimum fiber spacing in a hollow fiber bioreactor , 1988, Biotechnology and bioengineering.

[12]  A. Popel,et al.  Interactions of VEGF isoforms with VEGFR-1, VEGFR-2, and neuropilin in vivo: a computational model of human skeletal muscle. , 2007, American journal of physiology. Heart and circulatory physiology.

[13]  Alicia C B Allen,et al.  Multilayer microfluidic PEGDA hydrogels. , 2010, Biomaterials.

[14]  Jason P. Gleghorn,et al.  Microfluidic scaffolds for tissue engineering. , 2007, Nature materials.

[15]  C. Cooney,et al.  Model of oxygen transport limitations in hollow fiber bioreactors , 1991, Biotechnology and bioengineering.

[16]  Milica Radisic,et al.  Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers. , 2005, American journal of physiology. Heart and circulatory physiology.

[17]  A Krogh,et al.  The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue , 1919, The Journal of physiology.

[18]  Ioannis V. Yannas,et al.  Tissue and organ regeneration in adults , 2001 .

[19]  C D Murray,et al.  The Physiological Principle of Minimum Work: I. The Vascular System and the Cost of Blood Volume. , 1926, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Dai Fukumura,et al.  Tissue engineering: Creation of long-lasting blood vessels , 2004, Nature.

[21]  M. Yarmush,et al.  A novel formulation of oxygen‐carrying matrix enhances liver‐specific function of cultured hepatocytes , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  J. Pober,et al.  Engraftment of a vascularized human skin equivalent , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[23]  James G Truslow,et al.  Effect of mechanical factors on the function of engineered human blood microvessels in microfluidic collagen gels. , 2010, Biomaterials.

[24]  A. Khademhosseini,et al.  Microscale technologies for tissue engineering and biology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Tien,et al.  Computational design of drainage systems for vascularized scaffolds. , 2009, Biomaterials.

[26]  K. Lowe,et al.  Perfluorochemicals: their applications and benefits to cell culture. , 1998, Trends in biotechnology.

[27]  K. Chu,et al.  Bonding of macromolecular hydrogels using perturbants. , 2008, Journal of the American Chemical Society.

[28]  Joe Tien,et al.  Formation of perfused, functional microvascular tubes in vitro. , 2006, Microvascular research.

[29]  G. Arfken Mathematical Methods for Physicists , 1967 .

[30]  Joe Tien,et al.  Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. , 2007, Lab on a chip.

[31]  A Krogh,et al.  The supply of oxygen to the tissues and the regulation of the capillary circulation , 1919, The Journal of physiology.