Role of functionalized self-assembled peptide hydrogels in in vitro vasculogenesis

Abstract

Fabrication of vascularized tissue constructs plays an integral role in creating clinically relevant tissues. Scaffold materials should be sufficiently vascularized to mimic functional and complex native tissues. Herein, we report the development of bioactive and biomimetic self-assembled peptide (SAP) hydrogels that allow the rapid formation of a vascular structure in vitro. The KLDLKLDLKLDL (KLD peptide) SAP was functionalized with laminin derived peptides IKVAV (V1) and YIGSR (V2) through direct coupling to mimic the natural extracellular matrix (ECM) and human umbilical endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) cultured in 0.5% and 1% SAP hydrogels organized into vascularized structures. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) images proved the molecular integration of the nanofibrous structure in SAP hydrogels. The stability of SAP hydrogels was confirmed by rheological and degradation measurements. Bioactive peptide scaffolds enhanced significantly HUVEC/hMSC proliferation depicted by MTT analysis compared to KLD. Furthermore, the real time quantitative polymerase chain reaction (rt-PCR) was performed to analyse vascular gene expressions such as platelet/endothelial cell adhesion molecule-1 (PECAM-1), von Willebrand factor (vWF), and vascular endothelial cadherin (VE-cadherin). The results indicated that the KLD-V2 hydrogel significantly induced vasculogenesis in hMSC/HUVEC co-culture compared to KLD-V1, Biogelx and KLD because YIGSR in KLD-V2 promoted cell population and ECM secretion by the interaction with cells and increased vasculogenesis. Overall, the designed SAP hydrogel represents an effective scaffold for vascularization of tissue constructs with useful tissue engineering applications.