Issue 40, 2015

Tunable controlled release of bioactive SDF-1α via specific protein interactions within fibrin/nanoparticle composites

Abstract

The chemokine, stromal cell-derived factor 1α (SDF-1α), is a key regulator of the endogenous neural progenitor/stem cell-mediated regenerative response after neural injury. Increased and sustained bioavailability of SDF-1α in the peri-injury region is hypothesized to modulate this endogenous repair response. Here, we describe poly(lactic-co-glycolic) acid (PLGA) nanoparticles capable of releasing bioactive SDF-1α in a sustained manner over 60 days after a burst of 23%. Moreover, we report a biphasic cellular response to SDF-1α concentrations thus the large initial burst release in an in vivo setting may result in supratherapeutic concentrations of SDF-1α. Specific protein–protein interactions between SDF-1α and fibrin (as well as its monomer, fibrinogen) were exploited to control the magnitude of the burst release. Nanoparticles embedded in fibrin significantly reduced the amount of SDF-1α released after 72 h as a function of fibrin density. Therefore, the nanoparticle/fibrin composites represented a means to independently tune the magnitude of the burst phase release from the nanoparticles while perserving a bioactive depot of SDF-1α for release over 60 days.

Graphical abstract: Tunable controlled release of bioactive SDF-1α via specific protein interactions within fibrin/nanoparticle composites

Supplementary files

Article information

Article type
Paper
Submitted
16 May 2015
Accepted
07 Aug 2015
First published
11 Aug 2015
This article is Open Access
Creative Commons BY license

J. Mater. Chem. B, 2015,3, 7963-7973

Tunable controlled release of bioactive SDF-1α via specific protein interactions within fibrin/nanoparticle composites

D. Dutta, C. Fauer, H. L. Mulleneux and S. E. Stabenfeldt, J. Mater. Chem. B, 2015, 3, 7963 DOI: 10.1039/C5TB00935A

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