Engineering the microcirculation.

The ultimate survival of tissue-engineered constructs in vivo depends on the provision of an adequate blood supply to the engineered tissue and the capacity of the engineered microcirculation to connect with the existing recipient circulation. Techniques for the vascularization of tissue-engineered constructs can be broadly grouped into in vitro and in vivo approaches that rely on the presence of a pro-angiogenic microenvironment. Significant advances have been made in resolving the problem of microcirculatory network formation for large 3-dimensional constructs; however, issues concerning construct-host vessel connection, expansion of vascular volume accompanying growing tissue, and prevention of premature or excessive vascular regression remain to be resolved. This review provides an overview of current approaches to creating microcirculatory networks with respect to the cells involved, growth factors, growth factor delivery systems, and scaffold properties required to engineer a permanent microcirculatory network for tissue-engineered constructs. In addition, the review examines concerns related to vascular remodeling and regression reported in some tissue-engineering models.

[1]  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.

[2]  K. Alitalo,et al.  Molecular regulation of angiogenesis and lymphangiogenesis , 2007, Nature Reviews Molecular Cell Biology.

[3]  Hiroshi Takahashi,et al.  Enhanced inhibition of hepatitis B virus production by asialoglycoprotein receptor-directed interferon , 1999, Nature Medicine.

[4]  N. Ferrara,et al.  Molecular and biological properties of the vascular endothelial growth factor family of proteins. , 1992, Endocrine reviews.

[5]  J. Pearlman,et al.  Local perivascular delivery of basic fibroblast growth factor in patients undergoing coronary bypass surgery: results of a phase I randomized, double-blind, placebo-controlled trial. , 1999, Circulation.

[6]  Wayne A Morrison,et al.  An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue‐engineered construct , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  R. Lederman,et al.  Testing clinical therapeutic angiogenesis using basic fibroblast growth factor (FGF‐2) , 2003, British journal of pharmacology.

[8]  D J Mooney,et al.  Release from alginate enhances the biological activity of vascular endothelial growth factor. , 1998, Journal of biomaterials science. Polymer edition.

[9]  Y. Suárez,et al.  Vascularization and engraftment of a human skin substitute using circulating progenitor cell‐derived endothelial cells , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  Chad Johnson,et al.  The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. , 2004, Biomaterials.

[11]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[12]  R. Ross,et al.  Effects of growth factors in vivo. I. Cell ingrowth into porous subcutaneous chambers. , 1987, The American journal of pathology.

[13]  S. Weiss,et al.  Matrix Metalloproteinases Regulate Neovascularization by Acting as Pericellular Fibrinolysins , 1998, Cell.

[14]  P. D’Amore,et al.  Capillary growth: a two-cell system. , 1992, Seminars in cancer biology.

[15]  A. Khorana,et al.  FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis. , 2006, Blood.

[16]  F. Cui,et al.  The repair of brain lesion by implantation of hyaluronic acid hydrogels modified with laminin , 2005, Journal of Neuroscience Methods.

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

[18]  W A Morrison,et al.  Vascularisation of tissue-engineered grafts: the regulation of angiogenesis in reconstructive surgery and in disease states. , 2002, British journal of plastic surgery.

[19]  Axel R. Pries,et al.  Remodeling of Blood Vessels: Responses of Diameter and Wall Thickness to Hemodynamic and Metabolic Stimuli , 2005, Hypertension.

[20]  J. Winer,et al.  The vascular endothelial growth factor family of polypeptides , 1991, Journal of cellular biochemistry.

[21]  C. Hunt,et al.  Observations of the microcirculatory bed in rat mesocecum using differential interference constrast microscopy in vivo and electron microscopy. , 1976, The American journal of anatomy.

[22]  J. Kim,et al.  Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3'-Kinase/Akt signal transduction pathway. , 2000, Circulation research.

[23]  G. Wnek,et al.  Encyclopedia of biomaterials and biomedical engineering , 2008 .

[24]  H. Dvorak,et al.  Angiogenesis Therapy: Amidst the Hype, the Neglected Potential for Serious Side Effects , 2001, Circulation.

[25]  J. Fiddes,et al.  Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth , 1987, Nature.

[26]  G. Lip,et al.  Angiogenesis: basic pathophysiology and implications for disease. , 2003, European heart journal.

[27]  Y. Ikada,et al.  Accelerated tissue regeneration through incorporation of basic fibroblast growth factor-impregnated gelatin microspheres into artificial dermis. , 2000, Biomaterials.

[28]  J. Kelly,et al.  Generation of a vascularized organoid using skeletal muscle as the inductive source , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[29]  Pieter Koolwijk,et al.  Influence of fibrin structure on the formation and maintenance of capillary-like tubules by human microvascular endothelial cells , 2004, Angiogenesis.

[30]  Thomas N. Sato,et al.  Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. , 1997, Science.

[31]  J. Ware,et al.  Angiogenesis in ischemic heart disease , 1997, Nature Medicine.

[32]  D. Ingber,et al.  Mechanotransduction: All Signals Point to Cytoskeleton, Matrix, and Integrins , 2002, Science's STKE.

[33]  L. McIntire Vascular Assembly in Engineered and Natural Tissues , 2002, Annals of the New York Academy of Sciences.

[34]  K. Dutt,et al.  Three-dimensional model of angiogenesis: coculture of human retinal cells with bovine aortic endothelial cells in the NASA bioreactor. , 2003, Tissue engineering.

[35]  Haruchika Masuda,et al.  Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization , 1999, Nature Medicine.

[36]  M. Lampugnani,et al.  Fibrinogen induces endothelial cell adhesion and spreading via the release of endogenous matrix proteins and the recruitment of more than one integrin receptor. , 1990, Blood.

[37]  M. Gerritsen,et al.  Lumen Formation In Vivo Versus In Vitro Observations , 2003, Microcirculation.

[38]  Federica Boschetti,et al.  Synergy between interstitial flow and VEGF directs capillary morphogenesis in vitro through a gradient amplification mechanism. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[39]  T. Coenye,et al.  An epidemic Burkholderia cepacia complex strain identified in soil , 2002, The Lancet.

[40]  J. Isner,et al.  Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. , 1998, Circulation.

[41]  A. Perets,et al.  Enhancing the vascularization of three-dimensional porous alginate scaffolds by incorporating controlled release basic fibroblast growth factor microspheres. , 2003, Journal of biomedical materials research. Part A.

[42]  David J Mooney,et al.  Engineering vascular networks in porous polymer matrices. , 2002, Journal of biomedical materials research.

[43]  I. Yannas,et al.  Antigenicity and immunogenicity of collagen. , 2004, Journal of biomedical materials research. Part B, Applied biomaterials.

[44]  Judith M Curran,et al.  The use of poly(l-lactide) and RGD modified microspheres as cell carriers in a flow intermittency bioreactor for tissue engineering cartilage. , 2006, Biomaterials.

[45]  Geraldine Mitchell,et al.  The influence of architecture on degradation and tissue ingrowth into three-dimensional poly(lactic-co-glycolic acid) scaffolds in vitro and in vivo. , 2006, Biomaterials.

[46]  K J Gooch,et al.  Biomaterial-microvasculature interactions. , 2000, Biomaterials.

[47]  J. Quigley,et al.  Growth factor-induced angiogenesis in vivo requires specific cleavage of fibrillar type I collagen. , 2001, Blood.

[48]  E. Nabel,et al.  Recombinant fibroblast growth factor-1 promotes intimal hyperplasia and angiogenesis in arteries in vivo , 1993, Nature.

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

[50]  S. Rafii,et al.  Mobilization of Endothelial and Hematopoietic Stem and Progenitor Cells by Adenovector‐Mediated Elevation of Serum Levels of SDF‐1, VEGF, and Angiopoietin‐1 , 2001, Annals of the New York Academy of Sciences.

[51]  L Orci,et al.  In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices , 1983, The Journal of cell biology.

[52]  Robert Langer,et al.  Biodegradable Polymer Scaffolds for Tissue Engineering , 1994, Bio/Technology.

[53]  R. Langer,et al.  Tissue engineering: current state and perspectives , 2004, Applied Microbiology and Biotechnology.

[54]  A. Smit,et al.  Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial. , 2006, Human Gene Therapy.

[55]  J. Pober,et al.  Cytoprotection of Human Umbilical Vein Endothelial Cells Against Apoptosis and CTL-Mediated Lysis Provided by Caspase-Resistant Bcl-2 Without Alterations in Growth or Activation Responses1 , 2000, The Journal of Immunology.

[56]  C. Heeschen,et al.  Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. , 2003, Blood.

[57]  Y. M. Elçin,et al.  Controlled release of endothelial cell growth factor from chitosan-albumin microspheres for localized angiogenesis: in vitro and in vivo studies. , 1996, Artificial cells, blood substitutes, and immobilization biotechnology.

[58]  P. Kristjansen,et al.  Angiogenic synergy of bFGF and VEGF is antagonized by Angiopoietin-2 in a modified in vivo Matrigel assay. , 2004, Microvascular research.

[59]  J. Rhodin,et al.  The ultrastructure of mammalian arterioles and precapillary sphincters. , 1967, Journal of ultrastructure research.

[60]  Linda G Griffith,et al.  Engineering principles of clinical cell-based tissue engineering. , 2004, The Journal of bone and joint surgery. American volume.

[61]  P. Rogers,et al.  Blood Vessel Growth in the Endometrium , 1995, Microcirculation.

[62]  V. Backman,et al.  A biodegradable vascularizing membrane: a feasibility study. , 2007, Acta biomaterialia.

[63]  J M Anderson,et al.  Inflammatory response to implants. , 1988, ASAIO transactions.

[64]  Y. Tabata,et al.  Bioartificial Pancreas Transplantation at Prevascularized Intermuscular Space: Effect of Angiogenesis Induction on Islet Survival , 2003, Pancreas.

[65]  M. Shibata,et al.  Effects of shear stress on wound-healing angiogenesis in the rabbit ear chamber. , 1997, The Journal of surgical research.

[66]  D. Cheresh,et al.  Requirement of vascular integrin alpha v beta 3 for angiogenesis. , 1994, Science.

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

[68]  Laura E. Niklason,et al.  Replacement Arteries Made to Order , 1999, Science.

[69]  Juan P. Albar,et al.  Membrane Type 1-Matrix Metalloproteinase Is Activated during Migration of Human Endothelial Cells and Modulates Endothelial Motility and Matrix Remodeling* , 2001, The Journal of Biological Chemistry.

[70]  Y. Ikada,et al.  De novo formation of adipose tissue by controlled release of basic fibroblast growth factor. , 2000, Tissue engineering.

[71]  A. Barger,et al.  Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. , 1984, The New England journal of medicine.

[72]  B R Johansson,et al.  Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. , 1997, Science.

[73]  Andrés J. García,et al.  Inhibition of in vitro chondrogenesis in RGD-modified three-dimensional alginate gels. , 2007, Biomaterials.

[74]  W A Morrison,et al.  Formation of new tissue from an arteriovenous loop in the absence of added extracellular matrix. , 2000, Tissue engineering.

[75]  A. E. Elçin,et al.  Localized angiogenesis induced by human vascular endothelial growth factor-activated PLGA sponge. , 2006, Tissue engineering.

[76]  Anthony Atala,et al.  Controlled fabrication of a biological vascular substitute. , 2006, Biomaterials.

[77]  G Tellides,et al.  In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[78]  Julie H. Campbell,et al.  Development of tissue engineered vascular grafts. , 2007, Current pharmaceutical biotechnology.

[79]  Takayuki Asahara,et al.  Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb , 1996, The Lancet.

[80]  Y. Tabata,et al.  Maintenance of Neovascularization at the Implantation Site of an Artificial Device by bFGF and Endothelial Cell Transplant , 2006, Cell transplantation.

[81]  C. Garlanda,et al.  Heterogeneity of endothelial cells. Specific markers. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[82]  L. Niklason Techview: medical technology. Replacement arteries made to order. , 1999, Science.

[83]  G. Stevens,et al.  The Influence of Extracellular Matrix on the Generation of Vascularized, Engineered, Transplantable Tissue , 2001, Annals of the New York Academy of Sciences.

[84]  R. Jain,et al.  Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo , 2007, Nature Biotechnology.

[85]  Philippe Leboulch,et al.  Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2 , 2003, Nature Medicine.

[86]  A. Quyyumi,et al.  Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris. , 2000, The American journal of cardiology.

[87]  J. Isner,et al.  Stromal Cell–Derived Factor-1 Effects on Ex Vivo Expanded Endothelial Progenitor Cell Recruitment for Ischemic Neovascularization , 2003, Circulation.

[88]  W. Morrison,et al.  Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis. , 2007, The American journal of pathology.

[89]  Y. M. Elçin,et al.  Extensive in vivo angiogenesis following controlled release of human vascular endothelial cell growth factor: implications for tissue engineering and wound healing. , 2001, Artificial organs.

[90]  A. Desmoulière,et al.  Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. , 1995, The American journal of pathology.

[91]  W. Morrison,et al.  Implanted myoblast survival is dependent on the degree of vascularization in a novel delayed implantation/prevascularization tissue engineering model. , 2010, Tissue engineering. Part A.

[92]  R. C. Johnson,et al.  Neovascularization of synthetic membranes directed by membrane microarchitecture. , 1995, Journal of biomedical materials research.

[93]  H. Bøtker,et al.  NOGA-Guided Analysis of Regional Myocardial Perfusion Abnormalities Treated With Intramyocardial Injections of Plasmid Encoding Vascular Endothelial Growth Factor A-165 in Patients With Chronic Myocardial Ischemia: Subanalysis of the EUROINJECT-ONE Multicenter Double-Blind Randomized Study , 2005, Circulation.

[94]  Jeffrey R Capadona,et al.  Integrin specificity and enhanced cellular activities associated with surfaces presenting a recombinant fibronectin fragment compared to RGD supports. , 2006, Biomaterials.

[95]  R M Nerem,et al.  Tissue engineering a blood vessel substitute: the role of biomechanics. , 2000, Yonsei medical journal.

[96]  Peter Carmeliet,et al.  Angiogenesis in life, disease and medicine , 2005, Nature.

[97]  Z. Lokmic,et al.  Vascularization of Engineered Constructs , 2008 .

[98]  Y. Ouchi,et al.  VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B–PDGFRβ signaling , 2005, Journal of Cell Science.

[99]  A. Quyyumi,et al.  Basic fibroblast growth factor in patients with intermittent claudication: results of a phase I trial. , 2000, Journal of the American College of Cardiology.

[100]  B. Frerich,et al.  In vitro model of a vascular stroma for the engineering of vascularized tissues. , 2001, International journal of oral and maxillofacial surgery.

[101]  W M Reichert,et al.  Engineering the tissue which encapsulates subcutaneous implants. III. Effective tissue response times. , 1998, Journal of biomedical materials research.

[102]  U. Dirnagl,et al.  Estrogen Increases Bone Marrow‐Derived Endothelial Progenitor Cell Production and Diminishes Neointima Formation , 2003, Circulation.

[103]  W. Morrison,et al.  Generation of an autologous tissue (matrix) flap by combining an arteriovenous shunt loop with artificial skin in rats: preliminary report. , 2000, British journal of plastic surgery.

[104]  R. Lederman,et al.  Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial , 2002, The Lancet.

[105]  M J Yaszemski,et al.  Polymer concepts in tissue engineering. , 1998, Journal of biomedical materials research.

[106]  Shulamit Levenberg,et al.  Endothelial cells derived from human embryonic stem cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[107]  O. Volpert,et al.  Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1 , 2000, Nature Medicine.

[108]  Rakesh K Jain,et al.  Molecular regulation of vessel maturation , 2003, Nature Medicine.

[109]  J. Kelly,et al.  Contact with existing adipose tissue is inductive for adipogenesis in matrigel. , 2006, Tissue engineering.

[110]  K. Ueda,et al.  Tissue Engineering Skin Flaps: Which Vascular Carrier, Arteriovenous Shunt Loop or Arteriovenous Bundle, Has More Potential for Angiogenesis and Tissue Generation? , 2003, Plastic and reconstructive surgery.

[111]  O O Erol,et al.  New capillary bed formation with a surgically constructed arteriovenous fistula. , 1980, Plastic and reconstructive surgery.

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

[113]  Rui L Reis,et al.  Vascularization in bone tissue engineering: physiology, current strategies, major hurdles and future challenges. , 2010, Macromolecular bioscience.

[114]  D. Shima,et al.  The Mouse Gene for Vascular Endothelial Growth Factor , 1996, The Journal of Biological Chemistry.

[115]  Till Acker,et al.  Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions , 2001, Nature Medicine.

[116]  Aravinda Thiagalingam,et al.  Organization of Myocardial Activation During Ventricular Fibrillation After Myocardial Infarction: Evidence for Sustained High-Frequency Sources , 2005, Circulation.

[117]  Melody A Swartz,et al.  Engineered blood and lymphatic capillaries in 3‐D VEGF‐fibrin‐collagen matrices with interstitial flow , 2007, Biotechnology and bioengineering.

[118]  Julie H. Campbell,et al.  Tissue-Engineered Blood Vessels: Alternative to Autologous Grafts? , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[119]  Andrew J. Ewald,et al.  Matrix metalloproteinases and the regulation of tissue remodelling , 2007, Nature Reviews Molecular Cell Biology.

[120]  G. E. Gilbert,et al.  Slowed Release of Thrombin-cleaved Factor VIII from von Willebrand Factor by a Monoclonal and a Human Antibody Is a Novel Mechanism for Factor VIII Inhibition* , 1996, The Journal of Biological Chemistry.

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

[122]  E. Raines,et al.  Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. , 2000, Circulation research.

[123]  J. Converse,et al.  Inosculation of vessels of skin graft and host bed: a fortuitous encounter. , 1975, British journal of plastic surgery.

[124]  E. Keshet,et al.  Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis , 1992, Nature.

[125]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[126]  D. Kaplan,et al.  Biopolymer-based biomaterials as scaffolds for tissue engineering. , 2006, Advances in biochemical engineering/biotechnology.

[127]  Silviu Itescu,et al.  Cardiac Tissue Engineering in an In Vivo Vascularized Chamber , 2007, Circulation.

[128]  E. Keshet,et al.  A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. , 1998, Development.

[129]  Vladimir Mironov,et al.  Organ printing: tissue spheroids as building blocks. , 2009, Biomaterials.

[130]  Robert Langer,et al.  Local delivery of basic fibroblast growth factor increases both angiogenesis and engraftment of hepatocytes in tissue-engineered polymer devices1 , 2002, Transplantation.

[131]  Elisabetta Dejana,et al.  Endothelial cell–cell junctions: happy together , 2004, Nature Reviews Molecular Cell Biology.

[132]  W M Reichert,et al.  Engineering the tissue which encapsulates subcutaneous implants. II. Plasma-tissue exchange properties. , 1998, Journal of biomedical materials research.

[133]  N. Simionescu,et al.  The Cardiovascular System , 1983 .

[134]  D. Young,et al.  Species-specific in situ hybridization with fluorochrome-labeled DNA probes to study vascularization of human skin grafts on athymic mice. , 1996, The Journal of burn care & rehabilitation.

[135]  Susanne M. Smorenburg,et al.  Unfractionated and low molecular weight heparin affect fibrin structure and angiogenesis in vitro. , 2000, Cancer research.

[136]  M. Makuuchi,et al.  G-CSF stimulates angiogenesis and promotes tumor growth: potential contribution of bone marrow-derived endothelial progenitor cells. , 2002, Biochemical and biophysical research communications.

[137]  J. Ware,et al.  Long-term effects of surgical angiogenic therapy with fibroblast growth factor 2 protein. , 2002, The Journal of thoracic and cardiovascular surgery.

[138]  D. Vittet,et al.  In Vitro Models of Vasculogenesis and Angiogenesis , 2001, Laboratory Investigation.

[139]  J. Pober,et al.  Induction, differentiation, and remodeling of blood vessels after transplantation of Bcl-2-transduced endothelial cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[140]  Hyun Jung Chung,et al.  Heparin-immobilized biodegradable scaffolds for local and sustained release of angiogenic growth factor. , 2006, Journal of biomedical materials research. Part A.

[141]  Joan E Sanders,et al.  Tissue engineering of perfused microvessels. , 2003, Microvascular research.

[142]  R. Padera,et al.  Time course of membrane microarchitecture-driven neovascularization. , 1996, Biomaterials.

[143]  Judah Folkman,et al.  Angiogenesis in vitro , 1980, Nature.

[144]  J. Winer,et al.  The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. , 1991, Molecular endocrinology.

[145]  J. Vacanti,et al.  Silicon micromachining to tissue engineer branched vascular channels for liver fabrication. , 2000, Tissue engineering.

[146]  J. Isner,et al.  Endothelial Progenitor Cell Vascular Endothelial Growth Factor Gene Transfer for Vascular Regeneration , 2002, Circulation.

[147]  Bruce K Milthorpe,et al.  Engineering thick tissues--the vascularisation problem. , 2007, European cells & materials.

[148]  D E Ingber,et al.  Extracellular matrix controls tubulin monomer levels in hepatocytes by regulating protein turnover. , 1994, Molecular biology of the cell.

[149]  H. Vandenburgh,et al.  Recombinant Vascular Endothelial Growth Factor Secreted From Tissue-Engineered Bioartificial Muscles Promotes Localized Angiogenesis , 2001, Circulation.

[150]  A. Atala,et al.  In Vitro Systems for Tissue Engineering , 2002, Annals of the New York Academy of Sciences.

[151]  Holger Gerhardt,et al.  Endothelial-pericyte interactions in angiogenesis , 2003, Cell and Tissue Research.

[152]  R. Lang,et al.  Apoptosis during macrophage-dependent ocular tissue remodelling. , 1994, Development.

[153]  V. Dixit,et al.  Vascular Endothelial Growth Factor Induces Expression of the Antiapoptotic Proteins Bcl-2 and A1 in Vascular Endothelial Cells* , 1998, The Journal of Biological Chemistry.

[154]  P. Koolwijk,et al.  Role of Fibrin Matrix in Angiogenesis , 2001, Annals of the New York Academy of Sciences.

[155]  D. McDonald,et al.  Regulated angiogenesis and vascular regression in mice overexpressing vascular endothelial growth factor in airways. , 2004, The American journal of pathology.

[156]  M. Dake,et al.  Vascular endothelial growth factor enhances atherosclerotic plaque progression , 2001, Nature Medicine.

[157]  Holger Gerhardt,et al.  How do endothelial cells orientate? , 2005, EXS.

[158]  T. Skalak,et al.  The FASEB Journal express article 10.1096/fj.03-0933fje. Published online February 6, 2004. Multicellular simulation predicts microvascular patterning and in silico tissue assembly , 2022 .

[159]  K. Alitalo,et al.  VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia , 2003, The Journal of cell biology.

[160]  Kyunghee Choi,et al.  Evidence for the hemangioblast. , 2005, Experimental hematology.

[161]  Wayne A Morrison,et al.  Adipose tissue engineering based on the controlled release of fibroblast growth factor-2 in a collagen matrix. , 2006, Tissue engineering.

[162]  O. Wendler,et al.  Expression and function of laminins in the embryonic and mature vasculature. , 2005, Physiological reviews.

[163]  A. Griffioen,et al.  Molecular pathways of angiogenesis inhibition. , 2007, Biochemical and biophysical research communications.

[164]  J. Stingl Fine structure of precapillary arterioles of skeletal muscle in the rat. , 1976, Acta anatomica.

[165]  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.

[166]  S. Mahooti,et al.  Distinct signal transduction pathways are utilized during the tube formation and survival phases of in vitro angiogenesis. , 1998, Journal of cell science.

[167]  Melody A Swartz,et al.  Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro. , 2004, Microvascular research.

[168]  P. Sykes,et al.  How soon may the axial vessels of a surviving free flap be safely ligated: a study in pigs. , 1978, British journal of plastic surgery.

[169]  Jingsong Xu,et al.  Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo , 2001, The Journal of cell biology.

[170]  Y. Tabata,et al.  Recent progress in tissue engineering. , 2001, Drug discovery today.

[171]  A. Hess,et al.  The venous graft as an effector of early angiogenesis in a fibrin matrix. , 2008, Microvascular research.

[172]  Brigitte Vollmar,et al.  Inosculation: connecting the life-sustaining pipelines. , 2009, Tissue engineering. Part B, Reviews.

[173]  N. Ferrara The role of VEGF in the regulation of physiological and pathological angiogenesis. , 2005, EXS.

[174]  P. D’Amore,et al.  Cellular interactions in vascular growth and differentiation. , 2001, International review of cytology.

[175]  K. Yasuda,et al.  In situ regeneration of adipose tissue in rat fat pad by combining a collagen scaffold with gelatin microspheres containing basic fibroblast growth factor. , 2006, Tissue engineering.

[176]  Hyun Jung Chung,et al.  Heparin Immobilized Porous PLGA Microspheres for Angiogenic Growth Factor Delivery , 2006, Pharmaceutical Research.

[177]  David J Mooney,et al.  Comparison of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in SCID mice. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[178]  J. Hurley,et al.  Prefabrication of thin transferable axial-pattern skin flaps: an experimental study in rabbits. , 1990, British journal of plastic surgery.

[179]  M. Tanihara,et al.  Sustained release of basic fibroblast growth factor and angiogenesis in a novel covalently crosslinked gel of heparin and alginate. , 2001, Journal of biomedical materials research.

[180]  M. Endres,et al.  Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. , 2003, Circulation.

[181]  M C Davies,et al.  Interactions of 3T3 fibroblasts and endothelial cells with defined pore features. , 2002, Journal of biomedical materials research.

[182]  A. Sahni,et al.  Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation. , 2000, Blood.

[183]  C. Schmidt,et al.  Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering. , 2000, Biomaterials.

[184]  J. Isner,et al.  Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[185]  G. Stevens,et al.  New Murine Model of Spontaneous Autologous Tissue Engineering, Combining an Arteriovenous Pedicle with Matrix Materials , 2004, Plastic and reconstructive surgery.