Peptide REDV-modified polysaccharide hydrogel with endothelial cell selectivity for the promotion of angiogenesis

Rapid and controlled vascularization of engineered tissues remains one of the key limitations in thick tissue engineering. Although many studies have focused on improving the rapid vascularization through the immobilization of bioactive molecules, the competition in growth between endothelial cells (ECs) and other cell types is to some extent neglected. In this study, we developed a peptide GREDV-modified scaffold for selective adhesion of human umbilical vein endothelial cells (HUVECs) through the specific recognition of the REDV peptide and integrin α4 β1 . In vitro studies showed that GREDV-conjugated alginate (ALG-GREDV) improved HUVEC adhesion, migration and proliferation when compared with a non-modified group. Furthermore, ALG-GREDV exhibited a superior capability for promoting the proliferation and selective adhesion of HUVEC over that of other peptide (RGD and YIGSR) modified groups (ALG-Pep). In vivo angiogenic assays demonstrated that the ALG-GREDV scaffold induced an angiogenic potential by stimulating new vessel formation and showed the highest blood vessel density among all samples after 21 days of implanting (83.7 vessels/mm(2) ). More importantly, the blood vessel density in cambium fibrous tissue of ALG-GREDV was about 1.5 times greater than other ALG-Pep groups, indicating facilitation of ALG-GREDV on selective angiogenesis in vivo. These results demonstrated that REDV-conjugated alginate could be a useful scaffold for stimulating and inducing angiogenesis in tissue-engineered applications.