Tunable Controlled Release of Bioactive SDF-1? via Protein Specific Interactions within Fibrin/Nanoparticle Composites.

ABSTRACT: The chemokine, stromal cell-derived factor 1? (SDF-1?), is a key regulator of the endogenous neural progenitor/stem cell-mediated regenerative response after neural injury. Increased and sustained bioavailability of SDF-1? 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-1? in a sustained manner over 60days after a burst of 23%. Moreover, we report a biphasic cellular response to SDF-1? concentrations thus the large initial burst release in an in vivo setting may result in supratherapeutic concentrations of SDF-1?. Specific protein-protein interactions between SDF-1? 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-1? released after 72 hrs 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-1? for release over 60days.

SUBMITTER: Dutta D 

PROVIDER: S-EPMC4675172 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature