Sequential delivery of VEGF, FGF-2 and PDGF from the polymeric system enhance HUVECs angiogenesis in vitro and CAM angiogenesis.

Abstract

Angiogenesis is an organized series of events, beginning with vessel destabilization, followed by endothelial cell re-organization, and ending with vessel maturation. The formation of a mature vascular network requires precise spatial and temporal regulation of a large number of angiogenic factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor (PDGF). VEGF aids in vascular permeability and endothelial cell recruitment, FGF-2 activates endothelial cell proliferation and migration while PDGF stimulates vascular stability. Accordingly, VEGF may inhibit vessel stabilization while PDGF may inhibit endothelial cell recruitment. Therefore, a new polymeric system was prepared by the supercritical carbon dioxide foaming technology, which realized sequential delivery of two or more growth factors with the controlled dose and rate. Increased release of VEGF (71.10%) and FGF-2 (69.76%) compared to PDGF (43.17%) was observed for the first 7 days. Thereafter, up till 21 days, an increased rate of release of BMP-2 compared to VEGF 165 was observed. The effects of PDGF-PLAms/VEGF-FGF-2-PLGA scaffolds on angiogenesis were investigated by human umbilical vein endothelial cells (HUVECs) angiogenic differentiation in vitro and chorioallantoic membrane (CAM) angiogenesis in vivo. Sequential delivery of VEGF, FGF-2 and PDGF from structural polymer scaffolds with distinct kinetics resulted in significant angiogenic differentiation of HUVECs and rapid formation of mature vascular networks in chorioallantoic membrane. This study reported a composite scaffold with distinct release kinetics, and these results clearly indicated the importance of sequential delivery of multiple growth factors in tissue regeneration and engineering.

• Authors: Yan Bai, Lijuan Bai, Jing Zhou, Huali Chen, Liangke Zhang
• Journal: Cellular immunology (Cell Immunol) Vol. 323 Pg. 19-32 (01 2018) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 29111157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inducing Agents
• BMP2 protein, human
• Bone Morphogenetic Protein 2
• Delayed-Action Preparations
• Platelet-Derived Growth Factor
• Polyesters
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Fibroblast Growth Factor 2
• Polylactic Acid-Polyglycolic Acid Copolymer
• poly(lactide)

Topics

• Angiogenesis Inducing Agents (administration & dosage, metabolism)
• Bone Morphogenetic Protein 2 (metabolism)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Chorioallantoic Membrane
• Delayed-Action Preparations
• Drug Delivery Systems (methods)
• Fibroblast Growth Factor 2 (administration & dosage, metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Neovascularization, Physiologic (drug effects)
• Platelet-Derived Growth Factor (administration & dosage, metabolism)
• Polyesters (administration & dosage)
• Polylactic Acid-Polyglycolic Acid Copolymer (administration & dosage)
• Vascular Endothelial Growth Factor A (administration & dosage, metabolism)