Jump to main content
Jump to site search

Issue 34, 2014
Previous Article Next Article

Dually degradable click hydrogels for controlled degradation and protein release

Author affiliations

Abstract

Click reactions have emerged as one of the most powerful paradigms in materials chemistry owing to their high regioselectivity and efficient reaction yields under mild conditions. While stability of the bonds formed by these reactions often is highly valued, their controlled cleavage is promising as an elegant approach to engineer material degradation for a number of applications, including drug delivery and tissue engineering. However, cleavage of click linkages under physiological conditions remains a major challenge in the design of degradable biomaterials. Here, we demonstrate the use of cleavable click linkages formed by Michael-type addition reactions in conjunction with hydrolytically cleavable functionalities for the degradation of injectable hydrogels by dual mechanisms for controlled protein release. Specifically, the reaction between maleimides and thiols was utilized for hydrogel formation, where thiol selection dictates the degradability of the resulting linkage under thiol-rich reducing conditions. Relevant microenvironments would include those rich in glutathione (GSH), a tripeptide that is found at elevated concentrations in carcinoma tissues. Degradation of the hydrogels was monitored with rheometry and volumetric swelling measurements. Arylthiol-based thioether succinimide linkages underwent degradation via click cleavage and thiol exchange reaction in the presence of GSH as well as ester hydrolysis, whereas alkylthiol-based thioether succinimide linkages only undergo ester hydrolysis. The resulting control over the degradation rate within a reducing microenvironment resulted in ~2.5 fold differences in the release profile of cargo molecules (fluorescently labeled bovine serum albumin as a model protein) from dually degradable hydrogels compared to non-degradable hydrogels. These unique degradable chemistries are promising for controlling the rate of degradation and local release of therapeutic cargo molecules in cancer tissue microenvironments.

Graphical abstract: Dually degradable click hydrogels for controlled degradation and protein release

Back to tab navigation

Supplementary files

Publication details

The article was received on 28 Mar 2014, accepted on 06 Jun 2014 and first published on 08 Jul 2014


Article type: Paper
DOI: 10.1039/C4TB00496E
Author version
available:
Download author version (PDF)
J. Mater. Chem. B, 2014,2, 5511-5521

  •   Request permissions

    Dually degradable click hydrogels for controlled degradation and protein release

    P. M. Kharkar, A. M. Kloxin and K. L. Kiick, J. Mater. Chem. B, 2014, 2, 5511
    DOI: 10.1039/C4TB00496E

Search articles by author

Spotlight

Advertisements