Delivery of VEGF using collagen‐coated polycaprolactone scaffolds stimulates angiogenesis

Abstract

Establishing sufficient vascularization in scaffold remains a challenge for tissue-engineering. To improve angiogenesis, we incorporated vascular endothelial growth factor (VEGF) in collagen-coating over the porous polycaprolactone (PCL) scaffolds. The release kinetics of loaded VEGF from collagen-coated PCL (col-PCL) scaffolds was same as from scaffolds without the collagen. The bioactivity of VEGF delivered by the col-PCL scaffolds was confirmed by human umbilical vein endothelial cell (HUVEC) proliferation and chorioallantoic membrane (CAM) assay. The col-PCL scaffolds were implanted subcutaneously in mice for 7 and 14 days. At day 7, vascularization within scaffolds loaded with VEGF was superior to that in the scaffolds without VEGF. However, the vessel connectivity to host circulatory system was incomplete and restricted to the scaffold edges. At day 14, blood vessels in scaffolds reached density similar to the subcutaneous tissue and were perfusable throughout the implant thickness. Pre-washing the scaffolds with saline to remove the unbound growth factor decreased the initial burst release and sustained the VEGF-mediated angiogenesis in vivo. In conclusion, our study demonstrates that physically adsorbed VEGF stimulated angiogenesis in collagen-coated PCL scaffolds.

Injectable gelatin derivative hydrogels with sustained vascular endothelial growth factor release for induced angiogenesis

“…The in vivo bioactivity of VEGF released from the hydrogels was assessed by an open-shell chicken CAM assay[45]. Briefly, fertilized white leghorn chicken eggs (E0) were incubated at 37.8 °C for 3 days with 55-65% humidity, and the eggs were turned twice a day.…”

Recellularization of Rat Liver Scaffolds by Human Liver Stem Cells

“…[22][23][24][25] Nevertheless, in these synthetic scaffolds, the vessel connectivity to host circulatory system is incomplete and restricted to the scaffold edges when they are transplanted. 26 To solve these difficulties, natural scaffolds with intact tridimensional anatomical architecture have been successfully used recently for different organs, including the liver. 27 The natural extracellular matrices (ECMs) provide some advantages over the synthetic scaffolds.…”

Spatiotemporal Control of Vascular Endothelial Growth Factor Expression Using a Heat-Shock-Activated, Rapamycin-Dependent Gene Switch

“…The proteins are typically encapsulated within scaffolds or bound to the surface via electrostatic interactions or covalent conjugation. Methods of regulating growth factor release from such scaffolds generally include tuning the spontaneous, cellmediated, or physically inducible (e.g., light, enzyme, or drug) degradation of the scaffold (Leach et al, 2006;Kempen et al, 2009;Mercado et al, 2009;Jay et al, 2010;Singh et al, 2012). Although some success has been achieved with these approaches, they have certain inherent limitations, including restriction in the amount and stability of growth factor incorporated into the scaffold, inability to vary release kinetics in real time to compensate for a changing regeneration environment, and difficulties with repeated on/off control of factor release.…”