Improved Angiogenesis in Response to Localized Delivery of Macrophage-Recruiting Molecules

• Published in: PloS one 2015-07, Vol.10 (7), p.e0131643-e0131643
• Main Authors: Hsu, Chih-Wei, Poché, Ross A, Saik, Jennifer E, Ali, Saniya, Wang, Shang, Yosef, Nejla, Calderon, Gisele A, Scott, Jr, Larry, Vadakkan, Tegy J, Larina, Irina V, West, Jennifer L, Dickinson, Mary E
• Format: Article
• Language: English
• Subjects: Anastomosis; Angiogenesis; Angiogenesis Inducing Agents - pharmacology; Animals; Apoptosis; Artificial tissues; Becaplermin; Bioengineering; Biological products; Biomaterials; Biomedical engineering; Biomedical materials; Biophysics; Cell migration; Cell Movement - drug effects; Cell Movement - physiology; Cells, Cultured; Comparative analysis; Cornea - blood supply; Cornea - drug effects; Design factors; Employee recruitment; Endothelial Cells - drug effects; Endothelial Cells - physiology; Engineering; Fibroblast growth factor 2; Fibroblast Growth Factor 2 - pharmacology; Fibroblast growth factors; Fibroblasts; Growth factors; Human Umbilical Vein Endothelial Cells; Humans; Hydrogels; Macrophages; Macrophages - drug effects; Macrophages - physiology; Medicine; Mice; Microscopy; Neovascularization, Physiologic - drug effects; Organs; Physicians; Physiology; Polyethylene glycol; Polyols; Proto-Oncogene Proteins c-sis - pharmacology; Recruitment; Scaffolds; Studies; Surgical implants; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - pharmacology; Vascularization
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131643

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.