Improving the angiogenic potential of collagen matrices by covalent incorporation of Astragalus polysaccharides.

The high degree of degradation and the low angiogenic capabilities of temporary tissue substitutes still represent a major challenge in the field of tissue engineering. In an attempt to meet some of these challenges we covalently incorporated Astragalus polysaccharides, a plant extract with angiogenic properties, into collagen matrices. This contribution aims at developing a three-dimensional scaffold for temporarily covering tissue defects in tissue engineering and wound healing e.g. third degree burn wounds. Collagen matrices were modified by incorporating Astragalus polysaccharides (Ap) by means of covalent cross-linking with the watersoluble carbodiimide EDC. Matrices with different Ap/EDC ratios were prepared. After intensively washing of collagen matrices, the Ap modified and non-modified collagen matrices were exposed to the chorioallantoic membrane or implanted into subcutaneous pockets of rats. The number of capillaries in the chorioallantoic membrane in the vicinity of the samples, the hemoglobin contents within the explants and the hydroxyproline contents in the tissues attached to the explants were enhanced. Immunohistochemical evaluation of the explants revealed an increase in the recruitment of CD34+-cells in the modified matrices, indicative of improved angiogenic capabilities. To explore the underlying mechanisms, human umbilical vascular endothelial cells (HUVECs) were exposed to varying concentrations of Ap, collagen I and combinations thereof. The proliferative and chemotactic activities of HUVECs, as well as the protein expression of integrin αV, were strongly enhanced. The modification of collagen matrices with Astragalus polysaccharides of Ap with the cross-linking agent EDC leads to matrices with an increased angiogenic potential. The angiogenic capabilities of the modified collagen matrices appeared to depend on the Ap to EDC ratio. The presented results demonstrate that the incorporation of Astragalus polysaccharides into collagen matrices is an interesting and promising alternative for making wound dressings more angiogenic and improving their capabilities for covering tissue defects.