title: Improved Angiogenesis in Response to Localized Delivery of Macrophage-Recruiting Molecules.
abstract: Successful engineering of complex organs requires improved methods to promote rapid and stable vascularization of artificial tissue scaffolds. Toward this goal, tissue engineering strategies utilize the release of pro-angiogenic growth factors, alone or in combination, from biomaterials to induce angiogenesis. In this study we have used intravital microscopy to define key, dynamic cellular changes induced by the release of pro-angiogenic factors from polyethylene glycol diacrylate hydrogels transplanted in vivo. Our data show robust macrophage recruitment when the potent and synergistic angiogenic factors, PDGFBB and FGF2 were used as compared with VEGF alone and intravital imaging suggested roles for macrophages in endothelial tip cell migration and anastomosis, as well as pericyte-like behavior. Further data from in vivo experiments show that delivery of CSF1 with VEGF can dramatically improve the poor angiogenic response seen with VEGF alone. These studies show that incorporating macrophage-recruiting factors into the design of pro-angiogenic biomaterial scaffolds is a key strategy likely to be necessary for stable vascularization and survival of implanted artificial tissues.
authors.affiliation: Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Hsu
authors.affiliation: Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Poché
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas, United States of America.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Saik
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas, United States of America; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America.
authors.forename: Saniya
authors.initials: S
authors.lastname: Ali
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Shang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Nejla
authors.initials: N
authors.lastname: Yosef
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Gisele A
authors.initials: GA
authors.lastname: Calderon
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Larry
authors.initials: L
authors.lastname: Scott
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Tegy J
authors.initials: TJ
authors.lastname: Vadakkan
authors.affiliation: Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Larina
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas, United States of America; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
authors.affiliation: Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas, United States of America; Department of Bioengineering, Rice University, Houston, Texas, United States of America.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Dickinson
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020100:Hydrogels; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D020100:Hydrogels; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin