A modular self-assembly approach to functionalised β-sheet peptide hydrogel biomaterials.

Patrick J S King,Andrew Booth,Julie E Gough,M Giovanna Lizio,Aline F Miller,Richard F Collins,Simon J Webb

doi:10.1039/c5sm02039e

Patrick J S King, Andrew Booth + Show 5 more

Open Access

https://doi.org/10.1039/c5sm02039e

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Abstract

Two complementary β-sheet-forming decapeptides have been created that form binary self-repairing hydrogels upon combination of the respective free-flowing peptide solutions at pH 7 and >0.28 wt%. The component peptides showed little structure separately but formed extended β-sheet fibres upon mixing, which became entangled to produce stiff hydrogels. Microscopy revealed two major structures; thin fibrils with a twisted or helical appearance and with widths comparable to the predicted lengths of the peptides within a β-sheet, and thicker, longer, interwoven fibres that appear to comprise laterally-packed fibrils. A range of gel stiffnesses (G' from 0.05 to 100 kPa) could be attained in this system by altering the assembly conditions, stiffnesses that cover the rheological properties desirable for cell culture scaffolds. Doping in a RGD-tagged component peptide at 5 mol% improved 3T3 fibroblast attachment and viability compared to hydrogel fibres without RGD functionalisation.

Highlights

Hydrogels are a versatile class of material with applications in controlled drug release, cell delivery and tissue engineering
Our aim was to design a modular self-assembling peptidebased biomaterial with good biocompatibility that would form after the mixing of two precursor solutions at physiological pH, without the requirement for an external stimulus
Two-component protein/peptide hydrogels,[11] such as the MITCH system of Heilshorn and co-workers[12] or the complementary undecamers P11-13/P11-14 developed by Kyle et al.,2d are versatile as they can be formed around the cells of interest and can form the basis of injectable cell culture scaffolds.[13]

Summary

Introduction

Hydrogels are a versatile class of material with applications in controlled drug release, cell delivery and tissue engineering. The use of polymeric or self-assembled hydrogels as responsive cell culture materials[1] is promising, as the highly hydrated three dimensional structure provides a biomimetic environment for proliferating cells. Our aim was to design a modular self-assembling peptidebased biomaterial with good biocompatibility that would form after the mixing of two precursor solutions at physiological pH, without the requirement for an external stimulus. The external stimuli, such as heating or a pH change,[10] used to trigger the self-assembly of some hydrogels can be inimical to sensitive cell lines that cannot tolerate conditions either before or after the stimulus. A significant b-sheet component might give two-component hydrogels resistance to degradation by cells, yet allow the incorporation of responsive

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