title: Fibroblast-derived matrix (FDM) as a novel vascular endothelial growth factor delivery platform.
abstract: Vascular endothelial growth factor (VEGF) is one of the most important signaling cues during angiogenesis. Since many delivery systems of VEGF have been reported, the presentation of VEGF using a more physiologically relevant extracellular matrix (ECM), however, has yet to be thoroughly examined. In this study, we propose that fibroblast-derived extracellular matrix (FDM) is a novel platform for angiogenic growth factor delivery and that FDM-mediated VEGF delivery can result in an advanced angiogenic response. The FDMs, activated by EDC/NHS chemistry, were loaded with varying amounts of heparin. Different doses of VEGF were subsequently immobilized onto the heparin-grafted FDM (hep-FDM); 19.6 ± 0.6, 39.2 ± 3.2, and 54.8 ± 8.9 ng of VEGF were tethered using 100, 300, and 500 ng of initial VEGF, respectively. VEGF-tethered FDM was found chemoattractive and VEGF dose-dependent in triggering human umbilical vein endothelial cells (ECs) migration in vitro. When hep-FDM-bound VEGF (H-F/V) was encapsulated into alginate capsules (A/H-F/V) and subjected to release test for 28 days, it exhibited a significantly reduced burst release at early time point compared to that of A/V. The cell proliferation results indicated a substantially extended temporal effect of A/H-F/V on EC proliferation compared to those treated with soluble VEGF. For a further study, A/H-F/V was transplanted subcutaneously into ICR mice for up to 4 weeks to assess its in vivo effect on angiogenesis; VEGF delivered by hep-FDM was more competitive in promoting blood vessel ingrowth and maturation compared to other groups. Taken together, this study successfully engineered an FDM-mediated VEGF delivery system, documented its capacity to convey VEGF in a sustained manner, and demonstrated the positive effects of angiogenic activity in vivo as well as in vitro.
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; Dept. of Biomedical Engineering, University of Science and Technology, Daejeon 305-350, Republic of Korea.
authors.forename: Ping
authors.initials: P
authors.lastname: Du
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Mintai P
authors.initials: MP
authors.lastname: Hwang
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; Dept. of Biomedical Science, Kyung Hee University, Seoul 130-79, Republic of Korea.
authors.forename: Yong Kwan
authors.initials: YK
authors.lastname: Noh
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; Dept. of Biomedical Engineering, University of Science and Technology, Daejeon 305-350, Republic of Korea.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Subbiah
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: In Gul
authors.initials: IG
authors.lastname: Kim
authors.affiliation: Dept. of Bioengineering, Clemson University, SC 29634, USA.
authors.forename: Soon Eon
authors.initials: SE
authors.lastname: Bae
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; Dept. of Biomedical Engineering, University of Science and Technology, Daejeon 305-350, Republic of Korea. Electronic address: kpark@kist.re.kr.
authors.forename: Kwideok
authors.initials: K
authors.lastname: Park
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000254:growth & development; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000737:chemistry; D005347:Fibroblasts / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D041681:NIH 3T3 Cells; D018919:Neovascularization, Physiologic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D006493:Heparin
keywords: Alginate capsule (AC); Angiogenesis; Fibroblast-derived matrix (FDM); Heparin; Human umbilical vein endothelial cells (HUVECs); Vascular endothelial growth factor (VEGF)