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

D. Dutta, C. Fauer, H. L. Mulleneux, Sarah Stabenfeldt

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7963-7973
Number of pages11
JournalJournal of Materials Chemistry B
Volume3
Issue number40
DOIs
StatePublished - 2015

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ASJC Scopus subject areas

  • Biomedical Engineering
  • Medicine(all)
  • Chemistry(all)
  • Materials Science(all)

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