The study of angiogenesis stimulated by multivalent peptide ligand-modified alginate

Abstract

Enhancing the affinity of scaffolds for endothelial cell (EC) is a crucial procedure for promoting angiogenesis in tissue engineering. In this work, to achieve stronger binding affinity with ECs, the peptide sequence REDV was conjugated onto gold nanoparticles (AuNPs) to construct a multivalent ligand (cREDV). Then, the EC adhesion and proliferation were studied to determine ligand affinity for ECs in vitro. The results show that the cREDV-modified alginate (cREDV-ALG) surface exhibited a selective adhesion to human umbilical vein endothelial cells (HUVECs) compared with NIH 3T3 cells. The average area of individual HUVEC that adhered to cREDV-ALG was approximately 2.27-fold higher than that adhered to the monovalent REDV-modified alginate (REDV-ALG) surface. Additionally, a superior ability to promote the proliferation of HUVECs compared to the REDV-ALG surface was demonstrated. In vivo angiogenic assays were also carried out to assess the effect of multivalent strategy on the vascularization of scaffolds. The results illustrated that cREDV-ALG could stimulate new vessel formation in the scaffold, and the blood vessel density was at least 20% higher than that observed with monovalent REDV-ALG with a similar degree of ligand substitution. These results demonstrated that a multivalent ligand strategy was beneficial for the vascularization of engineered tissues.