Issue 5, 2014

One-pot synthesis of elastin-like polypeptide hydrogels with grafted VEGF-mimetic peptides

Abstract

Immobilization of growth factors to polymeric matrices has been a common strategy in the design of tissue engineering scaffolds to promote tissue regeneration, which requires complex cell signaling events with the surrounding matrix. However, the use of large protein growth factors in polymeric scaffolds is often plagued by immunogenicity, short in vivo half-lives, and reduced bioactivity. To address these concerns, we developed a single-step, cell-compatible strategy to tether small, growth-factor-mimetic peptides into a protein-engineered hydrogel with tunable biomaterial properties. Specifically, we covalently immobilized the QK peptide, an angiogenic peptide mimicking the receptor-binding region of vascular endothelial growth factor (VEGF), within tunable elastin-like polypeptide (ELP) hydrogels that include a cell-adhesive RGD sequence. Using a cell-compatible, amine-reactive crosslinker, we conducted a one-pot synthesis to simultaneously encapsulate cells while precisely controlling the QK grafting density (10 nM–100 μM) in the ELP hydrogels without altering other material properties. Fluorescence analysis of fluor-labeled QK peptides demonstrated that the conjugation efficiency to ELP hydrogels was >75% and that covalent immobilization effectively eliminates all QK diffusion. Compared with pristine ELP hydrogels, human umbilical vein endothelial cell (HUVEC) proliferation was significantly enhanced on ELP hydrogels immobilized with 10 nM or 1 μM QK. Moreover, upon encapsulation within tethered QK-ELP hydrogels, HUVEC spheroids maintained near 100% viability and demonstrated significantly more three-dimensional outgrowth compared to those supplemented with soluble QK peptide at the same concentration. These results encourage the further development of protein-engineered scaffolds decorated with growth-factor-mimetic peptides to provide long-term biological signals using this versatile, single-step synthesis.

Graphical abstract: One-pot synthesis of elastin-like polypeptide hydrogels with grafted VEGF-mimetic peptides

Article information

Article type
Paper
Submitted
16 Nov 2013
Accepted
28 Jan 2014
First published
04 Feb 2014

Biomater. Sci., 2014,2, 757-765

Author version available

One-pot synthesis of elastin-like polypeptide hydrogels with grafted VEGF-mimetic peptides

L. Cai, C. B. Dinh and S. C. Heilshorn, Biomater. Sci., 2014, 2, 757 DOI: 10.1039/C3BM60293A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements