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Baumann, L. ; Prokoph, S. ; Gabriel, C. ; Freudenberg, U. ; Werner, C. ; Beck-Sickinger, A. G.
A novel, biased-like SDF-1 derivative acts synergistically with star PEG -based heparin hydrogels and improves eEPC migration in vitro

The CXC chemokine stromal cell-derived factor-1a (SDF-1a, CXCL12) has been proven to recruit CXCR4 positive stem and progenitor cells of different sources to defected heart sites, with significant clinical benefits. However, the rapid proteolytic inactivation by inflammation-related proteases, inaccurate drug delivery or inappropriate local concentrations belong to the largest disadvantages for feasible application. Herein, we present a switchable, biased-like SDF-1a variant, AAV-[S4V]-SDF-1a, whose distinct activity is coupled to the inflammation-associated presence of dipeptidylpeptidase-4 (DPP-4), which cleaves an alanine-alanine dipeptide from the precursor. We decorated starPEG-heparin hydrogels with our novel SDF-1a variant and tested them for immobilization efficiency, time-dependent protein release as well as mobilization of early endothelial progenitor cells (eEPCs) in vitro. We found higher migration rates compared to conventional SDF-1a. In summary, we provide a conceptual work on cooperative effects of enzymatically activatable SDF-1a and starPEG-heparin hydrogels.

Source
Journal of Controlled Release 162, 68–75

DOI
http://dx.doi.org/10.1016/j.jconrel.2012.04.049

Published
June 2012
 
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