Du, Ping Hwang, Mintai P. Noh, Yong Kwan Subbiah, Ramesh Kim, In Gul Bae, Soon Eon Park, Kwideok 2024-01-20T08:31:03Z 2024-01-20T08:31:03Z 2021-09-02 2014-11-28 0168-3659 https://pubs.kist.re.kr/handle/201004/126092 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. (C) 2014 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV EXTRACELLULAR-MATRIX ALGINATE HYDROGELS IN-VITRO VEGF ANGIOGENESIS HEPARIN BINDING NEOVASCULARIZATION SCAFFOLDS PROTEINS Fibroblast-derived matrix (FDM) as a novel vascular endothelial growth factor delivery platform Article 10.1016/j.jconrel.2014.08.026 1 JOURNAL OF CONTROLLED RELEASE, v.194, pp.122 - 129 JOURNAL OF CONTROLLED RELEASE 194 122 129 scie scopus 000344229800012 2-s2.0-84907188034 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article EXTRACELLULAR-MATRIX ALGINATE HYDROGELS IN-VITRO VEGF ANGIOGENESIS HEPARIN BINDING NEOVASCULARIZATION SCAFFOLDS PROTEINS Angiogenesis Fibroblast-derived matrix (FDM) Human umbilical vein endothelial cells (HUVECs) Vascular endothelial growth factor (VEGF) Heparin Alginate capsule (AC)