Dual-peptide-modified alginate hydrogels for the promotion of angiogenesis

The ability to supply suitable blood vessel system is a major challenge for artificial thick tissue engineering. Angiogenesis is a key point during the process of microvascular formation. Many bioactive molecules such as extra cellular matrix(ECM) proteins and adhesion peptides derived from the ECM are applied to promote angiogenesis. In this work, two adhesion peptides, YIGSR and REDV, were selected to modify sodium alginate(ALG) to obtain YIGSR- and REDV-alginate conjugates(ALG-YIGSR, and ALG-REDV, respectively). We mixed the two peptide-conjugates together in a series of concentration ratios to prepare bioactive surfaces for in vitro studies and hydrogel scaffolds for in vivo studies. In vitro studies showed that surfaces modified with 1.09 pmol/mm2 peptide had the best affinity to human umbilical vein endothelial cells(HUVECs) than that with high or low concentrations of peptides. In addition, surfaces modified with dual peptides could significantly promote HUVECs proliferation, where ALG-YIGSR:ALG-REDV at a mole ratio of 5:1 exhibited the best enhancement ability. Furthermore, the in vivo angiogenesis results demonstrated that hydrogel scaffolds composed of mixed ALG-YIGSR and ALG-REDV at the 5:1 ratio had angiogenic induction potential by stimulating new blood vessel formation, and showed higher blood vessel density than scaffolds composed of a single peptide. These results demonstrated that a mixed combination of peptide alginate conjugates could be a potential scaffold to stimulate and induce angiogenesis in tissue engineering applications.