Synergistic Promotion of Blood Vessel Regeneration by Astragaloside IV and Ferulic Acid from Electrospun Fibrous Mats

The promotion of blood vessel initiation and growth plays an important role in the realization of therapeutic vascularization and regeneration of functional tissues. Astragalus membranaceus and angelica sinensis are commonly used traditional Chinese medicines for enriching the blood. In the current study astragaloside IV (AT, the main active ingredient of astragalus) and ferulic acid (FA, the main ingredient of angelica) were loaded into electrospun fibrous scaffolds to provide abundant and sustained biological factors required to initiate vascularization and bring it to maturity. The cell viability after AT and FA treatment was dose dependent with an optimal concentration of around 50 mu g/mL, and the most significant synergistic effect was demonstrated for the combined treatment with AT and FA with the ratio of 7/3 on both primary endothelial and smooth muscle cells. The in vitro release study showed that the amount of AT and FA release could be regulated by their loading amount and ratios in electrospun fibers. The localized and sustained codelivery of AT and FA indicated significantly high cell viability and secretion of extracellular matrices for both endothelial and smooth muscle cells, and induced significantly high densities of vascular structures after subcutaneous implantation. The most significant angiogenesis promotion with few inflammatory reactions was demonstrated for electrospun fibers containing AT and FA with the ratio of 7/3. It was suggested that the integration of the synergistic effect of Chinese medicine into electrospun fibrous scaffolds should provide clinical relevance for therapeutic vascularization, full vascularization in engineered tissues, and regeneration of blood vessel substitutes.