In vitro evaluation of Panax notoginseng Rg1 released from collagen/chitosan-gelatin microsphere scaffolds for angiogenesis

BACKGROUND The emergence of skin substitutes provides a new approach for the treatment of wound repair and healing. The consistent and steady release of angiogenic factors is an important factor in the promotion of angiogenesis in skin substitutes, which usually lack, yet need, a vascular network. METHODS In this study, ginsenoside Rg1, a natural compound isolated from Panax notoginseng (PNS), was incorporated into a collagen/chitosan-gelatin microsphere (CC-GMS) scaffold. The cumulative release kinetics were evaluated, and the effects of the released Rg1 on human umbilical vein endothelial cells (HUVECs) behavior, including proliferation, migration, tube formation, cell-cycle progression, cell apoptosis, and vascular endothelial growth factor (VEGF) secretion, were investigated. Additionally, HUVECs were cultured on the CC-GMS scaffold to test its biocompatibility. Standard Rg1 and VEGF were used as positive controls. RESULTS The results indicated that the CC-GMS scaffold had good release kinetics. The Rg1 released from the CC-GMS scaffold did not lose its activity and had a significant effect on HUVEC proliferation. Both Rg1 and VEGF promoted HUVEC migration and tube formation. Rg1 did not induce HUVEC apoptosis but instead promoted HUVEC progression into the S and G2/M phases of the cell cycle. Rg1 significantly increased VEGF secretion compared with that in the control group. HUVEC culture on the CC-GMS scaffold indicated that this scaffold has good biocompatibility and that CC-GMS scaffolds containing different concentrations of Rg1 promote HUVEC attachment in a dose- and time-dependent manner. CONCLUSIONS Rg1 may represent a new class of angiogenic agent that can be encapsulated in CC-GMS scaffolds to exert angiogenic effects in engineered tissue.