Issue 46, 2014

A CMP-based method for tunable, cell-mediated gene delivery from collagen scaffolds

Abstract

The use of collagen-based biomaterials in regenerative medicine has rapidly increased over the past decade. The unique structural and biochemical properties of collagen make it a particularly promising material for delivering both protein and DNA-based therapeutics. Although many collagen modification techniques have been developed, the majority of them require multi-step chemical treatments that can modify the natural favourable properties of collagen. We have developed a promising biomimetic modification technique employing collagen-mimetic peptides (CMP)s to control the retention and delivery of DNA polyplexes from collagen structures, including both monomeric 2-D collagen films and fibrous, 3-D gels. Variations in the concentration of CMPs displayed on polyplexes enabled tuning of polyplex retention vs. release over periods of at least 2 weeks on films and a month on gels. Retention of CMP-modified polyplexes (20 days) was substantially improved compared to non-modified polyplexes, which were retained for only 2 days. The activity of bound polyplex in collagen gels was shown, through a series of transfection studies, to be maintained in the presence of serum for a minimum of 2 weeks. Only matrix metalloproteinase (MMP)-stimulated cells exhibited significant levels of transfection suggesting that cell mobility within the gel was vital and that collagen remodelling played a role in stimulating gene release and expression. To our knowledge, this study is the first to deliver genes with CMP-modified polyplexes and to examine the effects of CMP display on DNA release. The results suggest that this technique may be used more broadly to create tuneable, collagen-based delivery systems.

Graphical abstract: A CMP-based method for tunable, cell-mediated gene delivery from collagen scaffolds

Supplementary files

Article information

Article type
Paper
Submitted
29 Leq 2014
Accepted
27 Dit 2014
First published
29 Dit 2014

J. Mater. Chem. B, 2014,2, 8174-8185

Author version available

A CMP-based method for tunable, cell-mediated gene delivery from collagen scaffolds

M. A. Urello, K. L. Kiick and M. O. Sullivan, J. Mater. Chem. B, 2014, 2, 8174 DOI: 10.1039/C4TB01435A

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