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Issue 40, 2015
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Tunable controlled release of bioactive SDF-1α via specific protein interactions within fibrin/nanoparticle composites

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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

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Publication details

The article was received on 16 May 2015, accepted on 07 Aug 2015 and first published on 11 Aug 2015


Article type: Paper
DOI: 10.1039/C5TB00935A
J. Mater. Chem. B, 2015,3, 7963-7973
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    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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