Supply of Nutrients to Cells in Engineered Tissues

Abstract A proper supply of nutrients to cells in engineered tissues is paramount for an optimal development and survival of these tissues. However, especially in tissues with clinically relevant sizes, the mass transport of nutrients into the tissue is often insufficient to sustain all the cells within the tissue. This is not only the case during in vitro culture. After implantation of an engineered tissue, a vascular network is not directly established. Therefore, the mass transport of nutrients is also critical during the initial period after implantation. This review introduces the basics of mass transport, leading to the conclusion that three main concepts can be used to increase nutrient supply in tissue engineering. These are; increasing the overall diffusion coefficient, decreasing the diffusion distance, or increasing convective transport. Based on these concepts, the main strategies that have been developed to enhance the supply of nutrients to cells in engineered tissues will be discussed.

[1]  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.

[2]  Pauline M. Doran,et al.  Bioprocess Engineering Principles , 1995 .

[3]  Buddy D. Ratner,et al.  Pore size controls angiogenesis in subcutaneously implanted porous matrices , 2004 .

[4]  R Langer,et al.  Dynamic Cell Seeding of Polymer Scaffolds for Cartilage Tissue Engineering , 1998, Biotechnology progress.

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

[6]  J. Tramper,et al.  Oxygen gradients in tissue‐engineered Pegt/Pbt cartilaginous constructs: Measurement and modeling , 2004, Biotechnology and bioengineering.

[7]  Adrian Neagu,et al.  Tissue engineering by self-assembly of cells printed into topologically defined structures. , 2008, Tissue engineering. Part A.

[8]  Anthony Atala,et al.  Oxygen producing biomaterials for tissue regeneration. , 2007, Biomaterials.

[9]  Lucie Germain,et al.  In vitro reconstruction of a human capillary‐like network in a tissue‐engineered skin equivalent , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  D. Hutmacher,et al.  Scaffolds in tissue engineering bone and cartilage. , 2000, Biomaterials.

[11]  Bojana Obradovic,et al.  Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model , 2000 .

[12]  A. Uchida,et al.  Growth of bone marrow cells on porous ceramics in vitro. , 1987, Journal of biomedical materials research.

[13]  R M Pilliar,et al.  Porous-surfaced metallic implants for orthopedic applications. , 1987, Journal of biomedical materials research.

[14]  D. Wendt,et al.  Computational evaluation of oxygen and shear stress distributions in 3D perfusion culture systems: macro-scale and micro-structured models. , 2008, Journal of biomechanics.

[15]  T. Ma,et al.  Oxygen tension influences proliferation and differentiation in a tissue-engineered model of placental trophoblast-like cells. , 2001, Tissue engineering.

[16]  A. Khademhosseini,et al.  Directed assembly of cell-laden microgels for fabrication of 3D tissue constructs , 2008, Proceedings of the National Academy of Sciences.

[17]  Anthony Atala,et al.  Oxygen generating scaffolds for enhancing engineered tissue survival. , 2009, Biomaterials.

[18]  Martin Fussenegger,et al.  Design of custom-shaped vascularized tissues using microtissue spheroids as minimal building units. , 2006, Tissue engineering.

[19]  M. Radisic,et al.  Chapter 12 – Cell nutrition , 2008 .

[20]  G. Whitesides,et al.  Self-Assembly at All Scales , 2002, Science.

[21]  Jos Malda,et al.  Heterogeneous proliferation within engineered cartilaginous tissue: the role of oxygen tension. , 2005, Biotechnology and bioengineering.

[22]  J. Dagorn,et al.  Expression of the stress-induced p8 mRNA is transiently activated after culture medium change. , 2001, European journal of cell biology.

[23]  Ingo Klimant,et al.  Determination of oxygen gradients in engineered tissue using a fluorescent sensor. , 2002, Biotechnology and bioengineering.

[24]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[25]  Robert Langer,et al.  Endothelialized microvasculature based on a biodegradable elastomer. , 2005, Tissue engineering.

[26]  Jeroen Rouwkema,et al.  Vascularization in tissue engineering. , 2008, Trends in biotechnology.

[27]  White Pr.  Cultivation of animal tissues in vitro in nutrients of precisely known constitution. , 1946 .

[28]  D. Mooney,et al.  Polymeric system for dual growth factor delivery , 2001, Nature Biotechnology.

[29]  Lucie Germain,et al.  Inosculation of Tissue‐Engineered Capillaries with the Host's Vasculature in a Reconstructed Skin Transplanted on Mice , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[30]  Fen Chen,et al.  Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds. , 2006, Tissue engineering.

[31]  M. Swartz,et al.  Interstitial flow and its effects in soft tissues. , 2007, Annual review of biomedical engineering.

[32]  P. Vermette,et al.  Enhancing oxygen solubility using hemoglobin- and perfluorocarbon-based carriers. , 2009, Frontiers in bioscience.

[33]  Alison P McGuigan,et al.  Vascularized Organoid Engineered by Modular Assembly Enables Blood Perfusion , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Patrick Vermette,et al.  Bioreactors for tissue mass culture: design, characterization, and recent advances. , 2005, Biomaterials.

[35]  Milica Radisic,et al.  Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue , 2006, Biotechnology and bioengineering.

[36]  Alison P McGuigan,et al.  Design criteria for a modular tissue-engineered construct. , 2007, Tissue engineering.

[37]  Dr. Morton H. Friedman.  Principles and Models of Biological Transport , 1986, Springer Berlin Heidelberg.

[38]  Ivan Martin,et al.  Angiogenesis in tissue engineering: breathing life into constructed tissue substitutes. , 2006, Tissue engineering.

[39]  D. Williams,et al.  Fracture toughness testing of biomaterials using a mini-short rod specimen design. , 1987, Journal of biomedical materials research.

[40]  Andreas Hess,et al.  Engineering of vascularized transplantable bone tissues: induction of axial vascularization in an osteoconductive matrix using an arteriovenous loop. , 2006, Tissue engineering.

[41]  N. Kotov,et al.  Three-dimensional cell culture matrices: state of the art. , 2008, Tissue engineering. Part B, Reviews.

[42]  S. Hollister.  Porous scaffold design for tissue engineering , 2005, Nature materials.

[43]  Antonios G. Mikos,et al.  Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[44]  L. Griffith,et al.  Capturing complex 3D tissue physiology in vitro , 2006, Nature Reviews Molecular Cell Biology.

[45]  David J. Mooney,et al.  Spatio–temporal VEGF and PDGF Delivery Patterns Blood Vessel Formation and Maturation , 2007, Pharmaceutical Research.

[46]  B Derby,et al.  Novel collagen scaffolds with predefined internal morphology made by solid freeform fabrication. , 2003, Biomaterials.

[47]  Ivan Martin,et al.  Method for Quantitative Analysis of Glycosaminoglycan Distribution in Cultured Natural and Engineered Cartilage , 1999, Annals of Biomedical Engineering.

[48]  Eliot R. Clark,et al.  Microscopic observations on the growth of blood capillaries in the living mammal , 1939 .

[49]  M. Csete,et al.  Oxygen in the Cultivation of Stem Cells , 2005, Annals of the New York Academy of Sciences.

[50]  Clemens A van Blitterswijk,et al.  Trends in biomaterials research: An analysis of the scientific programme of the World Biomaterials Congress 2008. , 2008, Biomaterials.

[51]  D. Wendt,et al.  The role of bioreactors in tissue engineering. , 2004, Trends in biotechnology.

[52]  A J Verbout,et al.  Design and fabrication of standardized hydroxyapatite scaffolds with a defined macro-architecture by rapid prototyping for bone-tissue-engineering research. , 2004, Journal of biomedical materials research. Part A.

[53]  C. V. van Blitterswijk,et al.  The use of endothelial progenitor cells for prevascularized bone tissue engineering. , 2009, Tissue engineering. Part A.

[54]  H. Awwad,et al.  Intercapillary distance measurement as an indicator of hypoxia in carcinoma of the cervix uteri. , 1986, International journal of radiation oncology, biology, physics.

[55]  J Tramper,et al.  The effect of PEGT/PBT scaffold architecture on oxygen gradients in tissue engineered cartilaginous constructs. , 2004, Biomaterials.

[56]  V. Mironov,et al.  Engineering biological structures of prescribed shape using self-assembling multicellular systems. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[57]  G. Schmid-Schönbein,et al.  Microlymphatics and lymph flow. , 1990, Physiological reviews.

[58]  D. Wendt,et al.  Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tensions. , 2006, Biorheology.